REPORT ON THE

GLOBAL ACTION PLAN

ON HIV DRUG RESISTANCE
2017–2021
REPORT ON THE
GLOBAL ACTION PLAN
ON HIV DRUG RESISTANCE
2017–2021
Report on the global action plan on HIV drug resistance 2017–2021

ISBN 978-92-4-007108-7 (electronic version)

ISBN 978-92-4-007109-4 (print version)

© World Health Organization 2023

Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO
licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).

Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the
work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses
any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you
must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work,
you should add the following disclaimer along with the suggested citation: “This translation was not created by the
World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original
English edition shall be the binding and authentic edition”.

Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of
the World Intellectual Property Organization (http://www.wipo.int/amc/en/mediation/rules/).

Suggested citation. Report on the global action plan on HIV drug resistance 2017–2021. Geneva: World Health Organization;
2023. Licence: CC BY-NC-SA 3.0 IGO.

Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris.

Sales, rights and licensing. To purchase WHO publications, see https://www.who.int/publications/book-orders.

To submit requests for commercial use and queries on rights and licensing, see https://www.who.int/copyright.

Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or
images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the
copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely
with the user.

General disclaimers. The designations employed and the presentation of the material in this publication do not imply the
expression of any opinion whatsoever on the part of WHO concerning the legal status of any country, territory, city or area
or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent
approximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or
recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted,
the names of proprietary products are distinguished by initial capital letters.

All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the
published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the
interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use.
 iii

CONTENTS
1. INTRODUCTION ............................................................................................................................................... 1
2. BACKGROUND ................................................................................................................................................ 2
3. PROGRESS ON HIV DRUG RESISTANCE PREVENTION AND RESPONSE .............................................................. 4
3.1 Prevention of HIV drug resistance .................................................................................................................. 5

3.2 Responses to high levels of pretreatment HIV drug resistance .................................................................... 8

4. PROGRESS ON MONITORING AND SURVEILLANCE ........................................................................................... 10

4.1 HIV drug resistance surveillance .................................................................................................................... 11

4.2 Monitoring early warning indicators of HIV drug resistance ........................................................................ 13

5. PROGRESS IN RESEARCH AND INNOVATION .................................................................................................... 14

6. PROGRESS IN STRENGTHENING LABORATORY CAPACITY ................................................................................ 16
6.1 HIV viral load testing ...................................................................................................................................... 17

6.2 HIV drug resistance testing ............................................................................................................................ 18

7. PROGRESS ON BUILDING SUSTAINABLE GOVERNANCE AND ENABLING MECHANISMS ...................................... 20

7.1 Advocacy and awareness ............................................................................................................................... 21

7.2 Funding HIV drug resistance activities ........................................................................................................... 21

7.3 Coordination, integration, alignment and country ownership ...................................................................... 22

8. QUALITATIVE INFORMATION OBTAINED FROM KEY STAKEHOLDER INTERVIEWS ABOUT THE GLOBAL ACTION
PLAN ON HIV DRUG RESISTANCE 2017–2021 ..................................................................................................... 24
8.1 Qualitative interview method ........................................................................................................................ 25

8.2 Interviewees’ perspectives: Global Action Plan on HIV drug resistance 2017–2021 ................................... 25

8.3 Interviewees’ perspectives: Global action plan on HIV drug resistance 2023–2030 ................................... 28

9. CONCLUSION .................................................................................................................................................. 29
REFERENCES ..................................................................................................................................................... 30
ANNEX 1. MONITORING FRAMEWORK AND OUTCOMES FOR THE GLOBAL ACTION PLAN ON HIV DRUG
RESISTANCE 2017–2021 .................................................................................................................................... 32
ANNEX 2. WHO AND PARTNER ORGANIZATIONS INTERVIEWED, BY WHO REGION ................................................. 33
iv

ACRONYMS
ART antiretroviral therapy

ARV antiretroviral

DTG dolutegravir

NNRTI non-nucleoside reverse-transcriptase inhibitor

NRTI nucleoside reverse-transcriptase inhibitor

PEPFAR United States President’s Emergency Plan for AIDS Relief

UNAIDS Joint United Nations Programme on HIV/AIDS

 1

1. INTRODUCTION
The Global Action Plan on HIV drug resistance 2017–2021 The plan’s successes, impact and shortfalls were assessed
provided a comprehensive framework for global and country using indicators established in Global Action Plan on HIV
action and outlined a package of interventions and resources drug resistance 2017–2021 and qualitative interviews of
to guide the collective response to HIV drug resistance. The key stakeholders at all levels. This report summarizes the
conclusion of this Global Action Plan on HIV drug resistance findings of the assessment.
at the end of 2021 offered an opportunity for WHO to
analyse the achievements realised over the preceding five
years and identify barriers to the plan’s implementation.

© WHO/Mark Nieuwenhof
2

2. BACKGROUND
Antimicrobial resistance is a major global public health
threat (1). Minimizing the emergence and transmission of HIV The goals of the Global Action Plan on HIV drug
drug resistance is a vital part of the global commitment to resistance 2017–2021 were to articulate synergistic
address the challenges of antimicrobial resistance (2). actions required to prevent HIV drug resistance from
undermining efforts to achieve global targets on
The Global Action Plan on HIV drug resistance 2017–2021
health and HIV and to provide the most effective
was a five-year framework connecting global and local
treatment to all people living with HIV, including
stakeholders in a coordinated response to HIV drug
adults, key populations, pregnant and breastfeeding
resistance (2). It articulated the collective and cooperative
women, children and adolescents.
actions required to prevent, monitor and respond to the
global threat posed by HIV drug resistance in populations
initiating and receiving antiretroviral therapy (ART).
The guiding principles of the Global Action Plan on HIV
WHO developed the Global Action Plan on HIV drug drug resistance were a public health approach, country
resistance 2017–2021 in collaboration with global and ownership, sustainable investment, standardized methods
national non-state partners, health ministry representatives, to monitor the emergence of HIV drug resistance and
researchers, community organizations, civil society and comprehensive, coordinated and integrated actions to tackle
donors. The Global Action Plan on HIV drug resistance HIV drug resistance (2).
2017–2021 was aligned with the Global Action Plan on
antimicrobial resistance adopted by the World Health The Global Action Plan on HIV drug resistance 2017–2021
Assembly in 2015 (3) and the Global Health Sector Strategy provided an action framework to be undertaken by countries,
on HIV 2016–2021 (4). global and national partners and WHO structured around
strategic objectives (Fig. 1) in five key areas: prevention
The Global Action Plan on HIV drug resistance 2017–2021 and response, monitoring and surveillance, research and
supported the commitments agreed upon at the United innovation, laboratory capacity and governance and
Nations High-Level Meeting on Ending AIDS to establish enabling mechanisms.
effective systems to monitor for, prevent and respond to
the emergence of drug-resistant HIV among people living
with HIV (2).

Fig. 1. The five strategic objectives of the Global Action Plan on HIV drug resistance
2017–2021

1 Prevention and response

Implement high-impact interventions to prevent and respond to HIV drug resistance.

Monitoring and surveillance

Obtain high-quality data on HIV drug resistance from periodic surveys, while expanding the coverage and quality of routine viral
2 load and HIV drug resistance testing to inform continuous HIV drug resistance surveillance; monitor the quality of service delivery;
and collect and analyse data recorded as part of routine patient care for the purpose of evaluating programme performance to
prevent HIV drug resistance.

Research and innovation

3 Encourage relevant and innovative research, leading to interventions that will have the greatest public health impact on
minimizing HIV drug resistance; and fill existing knowledge gaps on the risk of HIV drug resistance for newer ARV drugs and the
impact of service delivery interventions to increase viral load suppression and contain HIV drug resistance.

Laboratory capacity
4 Strengthen laboratory capacity and quality to support and expand the use of viral load monitoring and build capacity to monitor
HIV drug resistance in low- and middle-income countries.

Governance and enabling mechanisms

5 Ensure that governance and enabling mechanisms (advocacy, country ownership, coordinated action and sustainable funding)
are in place to support action on HIV drug resistance.
 3

Strategic objective 1 articulated the importance of Strategic objective 4 supported strengthening the laboratory
optimized procurement and supply chains for antiretroviral capacity for HIV drug resistance genotyping for surveillance
(ARV) drugs and viral load testing reagents and scale-up in low- and middle-income countries, facilitating in-country
and use of viral load testing to maximize population-level capacitation for HIV drug resistance testing for surveillance
viral load suppression among people receiving ART. and providing support for drug resistance testing in WHO-
In addition, strategic objective 1 highlighted the importance designated regional and specialized laboratories for countries
of adequate adherence support and the appropriate use of without HIV drug resistance testing capacity. In addition,
recommended ARV drugs. In addition, the Global Action strategic objective 4 underscored the need to strengthen
Plan on HIV drug resistance 2017–2021 articulated how the WHO HIV drug resistance laboratory network capacity
countries should develop plans to respond to rising levels to conduct resistance testing using dried blood spots and
of HIV drug resistance, including the transition to sequence the integrase region of the HIV-1 pol gene.
dolutegravir (DTG)-based first-line ART.
Strategic objective 5 defined governance and the enabling
Strategic objective 2 supported the collection and analysis mechanisms of advocacy, country ownership, coordinated
of data from nationally representative HIV drug resistance action and sustainable funding that were in place to
surveys and the collection and analysis of early warning initiate and sustain actions to address HIV drug resistance.
indicators of HIV drug resistance, a subset of globally In addition, strategic objective 5 emphasized integrating
recommended quality of care indicators predictive of viral HIV drug resistance prevention, monitoring and response
load suppression or HIV drug resistance in populations into long-term HIV programme planning and funding and
receiving ART (2, 5). linking it to national antimicrobial resistance strategies.

Strategic objective 3 encouraged relevant and innovative

research designed to close identified knowledge gaps related
to the risk of HIV drug resistance for newer ARV drugs and
to identify service delivery interventions that would increase
viral load suppression and minimize the emergence and
transmission of HIV drug resistance.

© WHO/Blink Media - Cindy Liu

4

3. PROGRESS ON HIV DRUG RESISTANCE

PREVENTION AND RESPONSE

© WHO/Harandane Dicko

STRATEGIC OBJECTIVE 1:
Implement high-impact interventions to prevent and respond to HIV drug resistance.
 5

3.1 Prevention of HIV drug resistance Countries’ response

Prevention of HIV drug resistance is a critical component • This report summarizes the outcomes of monitoring
of any national AIDS programme. It is achieved by using quality-of-care indicators associated with the emergence
WHO-recommended ARV drugs, optimizing ART service of HIV drug resistance in countries with a high burden
delivery and eliminating programmatic gaps to deliver of HIV infection from 2017 to 2021 (8). During this period,
ARV drugs in ways that minimize treatment interruptions 44 of 45 WHO focus countries reported data on ART
and maximize adherence. programme quality-of-care indicators through the
UNAIDS Global AIDS Monitoring system (9). Where
Opportunities for clinics and ART programmes to minimize available, viral load suppression data from the United
the possible emergence of HIV drug resistance may be States President’s Emergency Plan for AIDS Relief
identified through routine monitoring of programme (PEPFAR) population health indicator survey were used.
quality indicators associated with treatment failure and Country performance for each indicator was classified
drug resistance. Early warning indicator results provide using targets established for WHO early warning
clinic and programme managers with data about how indicators of HIV drug resistance. To provide as
their clinics perform compared with national means and minimally biased estimates as possible, only data from
with international targets to prevent the emergence of countries reporting nationally representative data or
HIV drug resistance. data derived from ≥70% of all ART clinics in the country
are summarized below. Note that not all countries
WHO’s response reported data on each of the outcome indicators, and
• In 2019, WHO published a technical brief for maintaining this is reflected in the variability of the denominators.
and improving the quality of care within HIV clinical Data on how well countries retain people receiving ART
services (6) to guide the implementation of high-quality 12 months after initiation were generally scarce or
HIV services through approaches to policy, strategy and infrequently reported. In 2019, the retention indicator
service delivery, to suggest considerations for selecting was revised to total attrition on ART, which has since
measures of high-quality services and to provide case been incorporated into WHO’s indicator guidance and
examples of quality management in HIV services in monitoring tools. However, the attrition indicator has not
low- and middle-income countries. yet been incorporated into Global AIDS Monitoring; thus,
the data are reported below for only 2017 and 2018.
• In 2021, WHO and Project ECHO, in partnership
with the WHO Quality of HIV Care Global Technical ° Adults: the proportion of countries with data was
Working Group, initiated a collaboration to host a 31% (14 of 45) in 2017, rising to 47% (21 of 45)
webinar series bringing together health policy-makers, in 2018. The proportion of countries meeting the
national programme managers, health-care providers, target of >85% of adults retained on ART after
donors and partners in interventions on HIV and 12 months was 36% (5 of 14) in 2017 and 29%
people living with HIV (7). An overall goal was to in 2018 (6 of 21).
stimulate discussions between various stakeholders Children: the proportion of countries with data
°
and share best practices and lessons learned to was 31% (14 of 45) in both 2017 and 2018.
improve the quality of care and life of people living The proportion of countries meeting the target
with HIV. Webinars have been held on community- >85% of children retained on ART was 29%
led monitoring and how it can contribute to improved (4 of 14) in 2017, rising to 43% in 2018 (6 of 14).
access to medicines, including preventing ARV drug
stock-outs and improving the quality of life for people • Viral load testing coverage
living with HIV. These webinars emphasize the need
for high-quality HIV care services along the entire ° Adults: the proportion of countries reporting data
cascade. They have featured locally led initiatives to on viral load testing coverage was 69% (31 of 45)
maximize the quality of service delivery, all of which in 2017, 91% (41 of 45) in 2018, 78% (35 of 45) in
directly or indirectly maximize population-level HIV 2019, 67% (30 of 45) in 2020 and 56% (25 of 45
viral suppression, thereby minimizing the preventable in 2021. The proportion of countries achieving the
emergence and transmission of drug-resistant HIV. target for viral load testing coverage of ≥70% of
adults receiving ART having at least one viral load
• Action briefs detailing initiatives in different countries test annually was 32% (10 of 31) in 2017, 41% (17
to improve the quality of HIV care delivered to of 41) in 2018 and rising to 43% (15 of 35) in 2019.
people living with HIV were released on the WHO However, in 2020 the proportion dropped to 37%
Global Learning Laboratory for Quality Universal (11 of 30) and rose modestly to 40% (10 of 25) in
Health Coverage in 2021 (https://www.who.int/ 2021. The decrease in viral load testing coverage in
news/item/09-12-2021-quality-of-hiv-care-from- 2020 may have been due to disruption in patient care
guidance-to-implementation). These briefs focus on or viral load testing reagent supply chain challenges
quality assurance and improvement applied to HIV because of the global COVID-19 pandemic.
programmes, their results and what was learned from
implementation experiences.
6

° Children: the proportion of countries with data on ° Children: the proportion of countries with available
viral load testing coverage was 42% (19 of 45) in data was 67% (30 of 45) in 2017 and 2018, 53%
2017, 64% (29 of 45) in 2018 and 2019, 51% (23 of (24 of 45) in 2019 and 58% (26 of 45) in 2020.
45) in 2020 and dropping to 29% (13 of 45) in 2021. The proportion of countries meeting the target of
The proportion of countries achieving the target zero drug stock-outs of routinely dispensed ARV
for viral load testing coverage ≥70% of children drug formulations for children was 53% (16 of 30) in
receiving ART receiving at least one viral load test 2017, 50% in 2018 (15 of 30), 54% in 2019 (13 of 24)
annually was 37% (7 of 19) in 2017, 38% (11 of 29) and 50% (13 of 26) in 2020.
in 2018, increasing to 59% (17 of 29) in 2019 but
dropping to 43% (10 of 23) in 2020 with a rebound • Proportion of people switching to second-line
to 77% (10 of 13) in 2021. For adults, the decrease ART is a proxy measure of how well a country uses viral
in viral load testing coverage in 2020 may have load to identify people for whom first-line ART is failing
been due to disruption in patient care or viral load and switching them to a second-line regimen, thereby
testing reagent supply chain challenges because of preventing the emergence and possible transmission of
the global COVID-19 pandemic, as highlighted in drug-resistant virus.
other reports. Adults: the proportion of countries reporting data
°
• Viral load suppression. Viral suppression was only was 62% (28 of 45) in 2017, 56% (25 of 45) in 2018
assessed among countries reporting levels of viral and 2019, 62% (28 of 45) in 2020 and 64% (29 of
load testing coverage ≥70% or a nationally 45) in 2021. The proportion of countries achieving
representative estimate. the target of having at least 5% of adults receiving
a second-line ART regimen was 43% (12 of 28) in
° Adults: The proportion of countries with 2017, 36% (9 of 25) in 2018 and 2019 and 46%
available data was 36% (16 of 45) in 2017, 24% (13 of 28) in 2020 and 45% (13 of 29) in 2021.
(11 of 45) in 2018, 27% (12 of 45) in 2019, 29%
(13 of 45) in 2020 and 20% (9 of 45) in 2021. ° Children: the proportion of countries reporting data
The proportion of countries achieving the target was 56% (25 of 45) in 2017, 51% (23 of 45) in 2018,
≥90% of adults receiving ART having a viral load 56% (25 of 45) in 2019 and 2020 and 60% (27 of 45)
testing documenting viral load ≤1000 copies/ml in 2021. The proportion of countries that achieved
was 25% (4 of 16) in 2017, 55% (6 of 11) in 2018, the target of having at least 5% of children receiving
50% (6 of 12) in 2019, 69% (9 of 13) in 2020 and ART receiving a second-line regimen was 76% (19
78% (7 of 9) in 2021. of 25) in 2017, 65% (15 of 23) in 2018, 80% (20 of
25) in 2019 and 2020 and 74% (20 of 27) in 2021.
° Children: the proportion of countries with available The high proportion of children receiving second-line
data was 16% (7 of 45) in 2017, 22% (10 of 45) treatment may reflect the use of protease inhibitors
in 2018, 38% (17 of 45) in 2019 and 18% (8 of 45) (PI) as first-line ART among children, with countries
in both 2020 and 2021. The proportion of countries reporting this as second-line ART.
achieving the target of ≥90% of children receiving
ART having a viral load test documenting viral load Overall, reporting indicators (Table 1) from countries
test result ≤1000 copies/ml was comparatively remain suboptimal, clearly underscoring a need to
lower in children than adults, with only 14% strengthen national and regional data reporting systems
(1 of 7) of countries achieving the target in 2017, for globally relevant indicators. The performance of
20% (2 of 10) in 2018, 18% (3 of 17) in 2019, programmatic quality indicators (Table 2) also remained
38% (3 of 8) in 2020 and 25% (2 of 8) in 2021. suboptimal in most countries during the reporting period,
especially for children, and was below the 2021 targets
• Drug stock-outs. Data on ARV drug stock-outs were established in the Global Action Plan on HIV drug resistance
reported for the years 2017–2020. As of 2021, the 2017–2021 (Annex 1). These findings underscore the need
indicator is being updated to reflect community-based for proactive approaches to improving the quality of HIV
and multimonth dispensing approaches. treatment and care services to minimize the emergence of
preventable drug-resistant HIV. Published examples from
° Adults: the proportion of countries with available countries documenting clinic and programme changes
data was 67% (30 of 45) in 2017 and 2018, implemented in response to early warning indicators
dropping to 53% (24 of 45) in 2019 and 58% (26 of monitoring include Cameroon, Ethiopia, Uganda and
45) in 2020. The proportion of countries meeting Zimbabwe (10-13). Examples of quality improvements
the target of zero drug stock-outs of routinely included strategies to strengthen data completeness and
dispensed ARV drugs was 50% (15 of 30) in 2017 reporting, optimized ARV drug dispensing practices to
and 2018 (15 of 30), 54% in 2019 (13 of 24) and follow global guidance, support for patient adherence to
50% (13 of 26) in 2020. therapy and minimalization of classification of lost to follow
up through enhanced documentation of clinic transfers.
 7

Table 1. Proportion of focus countries reporting data on quality-of-care indicators,

2017–2021 (n = 45)
Retention on ART 12
Proportion of patients switched
months after ART Viral load testing coverage Viral load suppression Drug stock-outs
Population Year to second-line ART
initiation

n % n % n % n % n %
2017 14 31 31 69 16 36 30 67 28 62
2018 21 47 41 91 11 24 30 67 25 56
Adults 2019 35 78 12 27 24 53 25 56
2020 30 67 13 29 26 58 28 62
2021 25 56 9 20 29 64
2017 14 31 19 42 7 16 30 67 25 56
2018 14 31 29 64 10 22 30 67 23 51
Children 2019 29 64 17 38 24 53 25 56
2020 23 51 8 18 26 58 25 56
2021 13 29 8 18 27 60

Table 2. Proportion of focus countries meeting targets of excellent performance on

quality-of-care indicators, 2017–2021
Retention on ART 12 months Proportion of patients switched
Viral load testing coverage Viral load suppression Drug stock-outs
Population Year after ART initiation to second-line ART
n/N % n/N % n/N % n/N % n/N %
2017 5/14 36 10/31 32 4/16 25 15/30 50 12/28 43
2018 6/21 29 17/41 41 6/11 55 15/30 50 9/25 36
Adults 2019 15/35 43 6/12 50 13/24 54 9/25 36
2020 11/30 37 9/13 69 13/26 50 13/28 46
2021 10/25 40 7/9 78 13/29 45
2017 4/14 29 7/19 37 1/7 14 16/30 53 19/25 76
2018 6/14 43 11/29 38 2/10 20 15/30 50 15/23 65
Children 2019 17/29 59 3/17 18 13/24 54 20/25 80
2020 10/23 43 3/8 38 13/26 50 20/25 80
2021 10/13 77 2/8 25 20/27 74

Excellent performance: targets for retention at 12 months (>85%), viral load testing coverage (≥70%), viral load suppression (≥90%), drug stock-outs (0%) and
proportion of people on second-line ART (≥5%).

© WHO/Tom Saater
8

3.2 Responses to high levels of Countries’ response

pretreatment HIV drug resistance • Pretreatment HIV drug resistance, prevalence of
NNRTIs ≥10%. Between 2014 and 2021, 26 of 35
The action framework of the Global Action Plan on HIV countries implementing surveys of pretreatment HIV
drug resistance 2017–2021 stressed the importance that drug resistance reported NNRTI resistance levels
WHO ensured normative guidance on the use of ARV exceeding 10% (17). All 26 countries have adopted
drugs for prevention and treatment was regularly updated, and implemented DTG-based first-line ART. The 2021
incorporating emerging evidence on resistance to new target established in the Global Action Plan on HIV
drug classes. Also, researchers were asked to generate drug resistance 2017–2021 was that 100% of countries
evidence regarding which public health interventions have responded to HIV drug resistance through adjusting
the most significant impact in preventing and responding programmes or revising national ART guidelines;
to HIV drug resistance, to be used for national and global therefore, the target was successfully achieved
decision-making. In addition, countries were encouraged (Annex 1).
to periodically review and update national policies and
protocols on using ARV drugs for HIV prevention and • High levels of HIV resistance to NNRTI drugs among
treatment based on WHO guidelines and the need to infants newly diagnosed with HIV. Between 2012
respond promptly to rising levels of HIV drug resistance. and 2020, 11 countries in Africa reported data to WHO
on levels of HIV drug resistance in infants less than 18
Researchers’ response months of age and ART naive (17). Levels of resistance
to efavirenz + nevirapine were very high, exceeding
In 2017, a modelling study predicted that failure to act on
50% in most countries, underscoring the urgent need to
increasing levels of pretreatment HIV drug resistance to
transition to WHO-recommended non-NNRTI-containing
non-nucleoside reverse-transcriptase inhibitor (NNRTI) drugs
regimens for young children. These 11 countries adopted
would lead to 5.7% more people dying from AIDS-related
lopinavir + ritonavir as the preferred first-line regimen.
causes, 3.5% more people acquiring HIV infection and a
Further, these countries are also shifting towards using
2.0% increase in expenditure for ART programmes during
DTG for infants ≥3 kg and ≥4 weeks of age following
the following five years (14).
the current WHO recommendations.
WHO’s response • Adoption of DTG-based ART as the preferred first-
In 2016, WHO published guidance to support countries line regimen. The number of countries adopting DTG
to respond to high levels (≥10%) of NNRTI pretreatment as part of the preferred first-line ART has steadily
resistance (15). The guidance emphasized accelerated increased. As of July 2022, 108 countries (88% of 123
transition to non-NNRTI-based ART (integrase inhibitor- reporting countries) had transitioned to DTG as part of
based treatment) and, in settings where the transition the preferred first-line ART for adults and adolescents
was not feasible, the guidance suggested considering an (Map 1). Also, 60 countries (55% of 110 reporting
individual HIV drug resistance test, if feasible, to guide countries) had adopted DTG-based antiretroviral therapy
the selection of optimal regimens among people initiating as part of the preferred first-line regimen for infants and
or reinitiating treatment. In 2018, WHO issued interim children (Map 2).
guidelines recommending DTG-containing ART as the
preferred first-line treatment in adolescents and adults, and
the 2021 guidelines update extends the recommendation to
use for children ≥3 kg and ≥4 weeks of age (16).
 9

Map 1. Adoption of DTG-based regimen as the preferred first-line ART in the national
guidelines for adults and adolescents, July 2022

Map 2. Adoption of DTG-based regimen as the preferred first-line ART in the national
guidelines for infants and children living with HIV, July 2022
10

4. PROGRESS ON MONITORING AND

SURVEILLANCE

© WHO/Muhd Ikmal Photography

STRATEGIC OBJECTIVE 2:
Obtain quality data on HIV drug resistance from periodic surveys, while expanding the coverage
and quality of routine viral load and HIV drug resistance testing to inform continuous HIV drug
resistance surveillance; monitor quality of service delivery and collect and analyse data recorded
as part of routine patient care for the purpose of evaluating programme performance to prevent
HIV drug resistance.
 11

4.1 HIV drug resistance surveillance • HIV drug resistance strategy. The WHO-
recommended HIV drug resistance surveillance,
The action framework of the Global Action Plan on HIV monitoring and response strategy was updated in
drug resistance 2017–2021 articulated WHO’s role in 2021 in response to changing country needs, evolving
developing guidelines for HIV drug resistance surveillance science and the introduction of new ARV drugs for
and monitoring and supporting countries in conducting the prevention and treatment of HIV (22). The 2021
HIV drug resistance surveillance and monitoring. WHO was update of the strategy included new survey methods
also responsible for strengthening the HIV drug resistance of acquired HIV drug resistance, focusing on DTG
surveillance data repository and management. In addition, resistance and new survey methods for countries
WHO was asked to report global and regional levels of HIV scaling up PrEP (18).
drug resistance and trends regularly.
• HIV drug resistance reports. WHO promotes the
Countries were encouraged to implement periodic nationally dissemination and sharing of health data to advance
representative surveys to estimate the prevalence of public health by permitting analysis that enables the
drug-resistant HIV and to disseminate HIV drug resistance fullest possible understanding of health challenges to
survey results in the country and to WHO for timely public help to develop new solutions and ensure that decisions
health assessment. are based on the best available evidence. From 2017 to
2021, WHO produced three global reports and maps on
WHO’s response HIV drug resistance prevalence and trends based on the
information shared by countries (17, 23, 24). The target
• HIV drug resistance surveillance methods. To assist
established in the monitoring framework for the Global
countries with HIV drug resistance surveillance, new
Action Plan on HIV drug resistance 2017–2021 (Annex 1)
standardized methods and operational toolkits were
was therefore achieved (two WHO reports published
developed, including:
by 2021).
° HIV drug resistance surveillance in countries scaling
• Country support to conduct HIV drug resistance
up pre-exposure prophylaxis (18);
surveillance: From 2017 to 2021, WHO provided
° Laboratory-based survey of acquired HIV drug technical assistance to 81 countries for the surveillance
resistance using remnant viral load specimens (19); of HIV drug resistance (Map 3). Based on countries’
requests, WHO facilitated the development of protocols,
° Clinic-based survey of acquired HIV drug resistance training and surveys implementation, database use,
(20); and data quality assurance, analysis and interpretation and
country reports drafting and dissemination.
° Sentinel surveillance of acquired HIV resistance in
populations receiving ART (21).

• HIV drug resistance database. WHO has developed

an HIV drug resistance database as a global repository
of HIV drug resistance survey data, which includes
deidentified individual-level epidemiological information
linked to HIV genome sequences. The database has four
main purposes: (1) quality assurance of epidemiological
and sequence data; (2) to ensure standardized
interpretation of resistance by linking to the most recent
algorithm for interpreting these data; (3) to support
the dissemination of data for global reporting; and (4)
to provide a long-term, secure repository for data on
resistance to HIV drugs.
12

Map 3. Country support and technical assistance provided by WHO for the surveillance
of HIV drug resistance, 2017–2021

Countries’ response
Substantial progress in survey implementation has been • Six surveys of HIV drug resistance among treatment-
achieved since 2014, with 56 countries implementing naive infants were implemented in six countries between
139 surveys. Between 2017 and 2021, 106 surveys were 2017 and 2021 (some recent surveys have not been
implemented in 43 countries versus 33 surveys in 23 finalized) versus four surveys in four countries between
countries between 2014 and 2016 (Map 4). 2014 and 2016.

• Thirty-nine pretreatment drug resistance surveys • Sixty-one surveys of acquired HIV drug resistance were
were implemented in 38 countries between 2017 and implemented in 30 countries between 2017 and 2020
2021 versus 17 surveys in 17 countries between 2014 versus 12 surveys in seven countries between 2014
and 2016. and 2016.
 13

Map 4. Implementation of national HIV drug resistance surveys, 2004–2021

4.2 Monitoring early warning indicators associated with HIV drug resistance at the clinic-level.
The proportion of countries implementing early warning
of HIV drug resistance at the clinic level indicators monitoring and reporting data declined from 36%
(8 of 22) in 2018 to 29% (8 of 28) in 2019, 28% (9 of 32) in
WHO’s response 2020 and 21% (6 of 28) in 2021. The target established in
WHO recommends that programmes routinely monitor the monitoring framework for the Global Action Plan on HIV
the quality-of-care indicators known as early warning drug resistance 2017–2021 (Annex 1) was therefore not
indicators of HIV drug resistance at the national and clinical achieved (≥90% of the 45 WHO focus countries monitored
levels. Routine monitoring of quality-of-care indicators and the early warning indicators in 2021).
response to suboptimal performance form the foundation of The decline in indicator monitoring and reporting highlights
HIV drug resistance prevention and link WHO-recommended a need for increased advocacy of the importance of frequent
surveillance of HIV drug resistance to programmatic quality-of-care indicator monitoring and prompt response
interventions designed to minimize it. to suboptimal performance to improve the quality of service
The early warning indicators use standardized definitions, delivery at the clinic and programmatic levels.
which have evolved as programmes mature and public Integration of early warning indicators into the routine
health actions are refined. A consultative process led by clinic and programme monitoring and evaluation systems,
WHO was used to update the indicators included in the followed by rapid investigation and response to suboptimal
2020 WHO consolidated HIV strategic information guidelines performance, may increase early warning indicators
(25). The most up-to-date early warning indicators for monitoring and enable clinics and programmes to close gaps
HIV drug resistance were included in the WHO HIV drug in service delivery. As of 2021, 75% (18 of 24) of countries
resistance surveillance, monitoring and response strategy reporting data have integrated early warning indicators into
updated in 2021 (22). routine monitoring and evaluation systems in accordance
with the WHO recommendations. However, many countries
Countries’ response
still need to report data.
Between January 2018 and December 2021, 51% (23 of 45)
of the 45 countries with a high burden of HIV infection
reporting data to the UNAIDS Global AIDS Monitoring
system monitored programme early warning indicators
14

5. PROGRESS IN RESEARCH AND INNOVATION

© WHO Thailand

STRATEGIC OBJECTIVE 3:
Encourage relevant and innovative research, leading to interventions that will have the greatest
public health impact on minimizing HIV drug resistance; fill existing knowledge gaps on the risk
of HIV drug resistance for newer ARV drugs and the impact of service delivery interventions to
increase viral load suppression and contain HIV drug resistance.
 15

Relevant and innovative research is vital to address Research topics considered the highest priority within the
knowledge gaps and create interventions that significantly five-year plan were ranked as tier 1. Topics deemed less
minimize HIV drug resistance. The Global Action Plan on critical over the next five years were ranked as tier 2.
HIV drug resistance 2017–2021 tasked WHO to convene
a research priority-setting process in collaboration with Researchers’ response
research institutions and expert networks. Also, researchers
The monitoring framework for the Global Action Plan on
were encouraged to address the research gaps related to HIV
HIV drug resistance 2017–2021 defined the research and
drug resistance.
innovation indicator target as ≥50% of research gaps
WHO’s response identified by the expert meeting convened by WHO in 2017
should have at least one investigation planned or initiated.
In 2017, WHO convened an expert meeting to identify The research community addressed all but two of the gaps
research gaps and areas of innovation for prevention, identified by the expert meeting convened by WHO in 2017
monitoring and addressing concerns on HIV drug resistance. (Table 3). Therefore, the target was exceeded, with 92% of
Overall, the group identified priority gaps grouped around the identified research gaps related to HIV drug resistance
three main themes: (1) epidemiological and clinical, being addressed by the research community by the end of
(2) virological and (3) innovative technologies with a 2021 (Annex 1).
specific focus on the transition to DTG-based ART (Table 3).

Table 3. Summary of progress in addressing research gaps related to HIV drug resistance
Epidemiology and clinical aspects
• Effect of pre-existing resistance to the nucleoside reverse-transcriptase inhibitor (NRTI) backbone on the efficacy of DTG-based ART
Levels of viral suppression and prevalence and pattern of HIV drug resistance mutations among people for whom DTG-based ART is
•
failing in low- and middle-income countries
Cost–effectiveness of individualized HIV drug resistance testing for people for whom a boosted PI or DTG-based regimen is failing to
•
minimize unnecessary switches to subsequent lines
• HIV drug resistance emerging in programmes scaling up PrEP
• Impact of K65R/M184V mutations on the efficacy of tenofovir disoproxil fumarate (TDF)- and emtricitabine (FTC)-based PrEP
Validated local, inexpensive and sustainable corrective actions to minimize the emergence and transmission of preventable
•
drug-resistant HIV
• Clinical impact of raltegravir-based ART among children infected with NRTI-resistant HIV
• Clinical impact of DTG administered twice daily among children for whom raltegravir-based ART is failing
• Optimal viral load switching algorithm to minimize the emergence of resistance
• Simple algorithm for interpreting HIV drug resistance for use by caregivers
Efficacy of DTG administered twice daily as a strategy to increase the potency of the regimen among individuals with partly active
•
NRTI backbone
Levels of viral suppression and acquired HIV drug resistance among people receiving second-line boosted PIs in low- and
•
middle-income countries, with particular focus on atazanavir + ritonavir
Response of TDF, lamivudine and DTG in populations at high risk of suboptimal adherence (such as adolescents) and among people
•
coinfected with tuberculosis and HIV
• Clinically significant thresholds of low-abundance NNRTI-resistant variants
• Cost–effectiveness analysis tools for use in countries for financing and advocacy of optimized treatment
Virological aspects
• Correlation of genotype-phenotype and clinical significance for all mutations
• List of transmitted integrase inhibitor mutations
Minimum set of mutations for PIs, reverse-transcriptase inhibitors and integrase inhibitors for clinical purposes for point-mutation
•
technology
• Impact of novel drug delivery methods (such as long-acting drug formulations) on the selection of HIV drug resistance
Innovative technologies
• Simple and affordable point-of-care HIV drug resistance assays
Inexpensive, simple, easy-to-interpret tests that combine viral load and HIV drug resistance testing that can be used to minimize
•
unnecessary switches to subsequent regimens
• Simple and affordable next-generation sequencing bioinformatics algorithms
• Newer collection matrices for HIV drug resistance testing
Affordable, simple and easy-to-use point-of-care tests to measure drug levels to distinguish people for whom treatment is failing
•
because of poor adherence versus resistance

Methods: rapid assessment of research question implementation among the research community and review of published literature. Research topics considered
the highest priority within the five-year plan were ranked as tier 1. Topics deemed less critical over the next five years were ranked tier 2.

• Tier 1 research question • Tier 2 research question Research currently undergoing No evidence that research is being conducted
16

6. PROGRESS IN STRENGTHENING
LABORATORY CAPACITY

© WHO Thailand

STRATEGIC OBJECTIVE 4:
Strengthen laboratory capacity and quality to support and expand use of viral load monitoring
and build capacity to monitor HIV drug resistance in low- and middle-income countries.
 17

6.1 HIV viral load testing • Toolkit: HIV molecular diagnostics toolkit to improve
access to viral load testing and infant diagnosis:
Early identification of patients experiencing failure to HIV treatment and care (27); and
suppress viral loads and their appropriate management
reduces the risk of emergence, accumulation and • Module for assessing and strengthening the quality
transmission of drug resistance variants. It ensures good of viral load testing data within HIV programmes and
treatment response and the prevention of onward HIV patient monitoring systems: implementation tool (28).
transmission. For this reason, expanding access and optimal
use of viral load testing is a critical measure for preventing
Countries’ response
HIV drug resistance. Majority of the countries within low- and middle-income
countries have a nation-wide policy for routine viral load
The action framework of the Global Action Plan on HIV drug
monitoring for adults and adolescents, with 74% (91 of 123)
resistance 2017–2021 included WHO’s technical assistance to
reporting implementation in >95% of clinic sites; of the
countries to generate quality-assured viral load test results.
remainder, almost half (47%, 15 of 32) reported implementation
Also, countries were encouraged to ensure the availability
in many (50–95%) treatment sites (Map 5).1
of high-quality viral load testing, including prompt reporting
and the use of results for clinical care. Nevertheless, viral load testing coverage remains suboptimal
among the 45 HIV high-burden countries reporting data to
WHO’s response WHO; 88% (22 of 25) had viral load testing coverage below
To assist countries to generate quality-assured viral load 90% in 2021. Moreover, 32% of the countries reported
test results, WHO published the following guidance from ≤50% viral load testing coverage in 2021. This is, however,
2017 to 2021: a slight improvement from 2018, 2019, and 2020 where
40%, 34% and 36% of the countries reported viral load
• Technical update: considerations for developing a testing coverage of ≤50%. More efforts are, however,
monitoring and evaluation framework for viral load needed to ensure universal access and effective utilization
testing: collecting and using data for scale-up and of viral load tests in low- and middle-income countries.
outcomes (26);

Map 5. National policy on routine viral load testing for monitoring ART and
implementation status among adults and adolescents living with HIV in low- and
middle-income countries, July 20222

1
Low and middle-income countries defined by the World Bank income categorisation.
2
The map illustrates reported country policy but not necessarily compliance to stated policy.
18

6.2 HIV drug resistance testing WHO is steering a diagnostic testing agenda for the future
development of affordable HIV drug resistance tests for
High-quality HIV drug resistance testing is critical for the individual patient management in specific use cases in
surveillance of HIV drug resistance at a population level. low- and middle-income countries. This initiative follows the
Therefore, the action framework of the Global Action Plan increased use of HIV drug resistance testing for individual
on HIV drug resistance 2017–2021 encouraged countries to patient monitoring in low- and middle-income countries.
designate a laboratory for HIV drug resistance testing, build Among 34 countries with a high burden of HIV reporting
capacity and apply for membership in the WHO HIVResNet data to WHO, 23 (68%) have a policy recommending HIV
Laboratory Network. In addition, the framework underscored drug resistance testing for individual patient management.
the importance of expanding and strengthening the capacity
of the WHO HIVResNet Laboratory Network to conduct To support this diagnostic agenda, WHO convened a series
resistance testing to newer drug classes, including integrase of consultations between July 2021 and November 2022
inhibitors, and to use field-friendly specimens such as dried to develop a target product profile for HIV drug resistance
blood spots. tests for patient management in low- and middle-income
countries. The target product profile is expected to be
WHO’s response completed in 2023.

The WHO HIVResNet Laboratory Network performs drug WHO HIVResNet’s response
resistance testing for countries implementing HIV drug
resistance surveillance. The WHO HIVResNet Laboratory The WHO HIVResNet HIV drug resistance laboratory
Network supports HIV drug resistance surveillance by operational framework classifies the laboratories into
providing accurate and timely genotyping results that meet national, regional and specialized. National laboratories
WHO specifications. Its objectives are to ensure the proper perform HIV drug resistance testing for surveys in their
collection, handling, shipment and storage of specimens and country. Regionally designated laboratories perform
the availability of quality-assured HIV genotyping laboratory testing for surveys within their region for countries without
services producing comparable and reliable results at the nationally designated laboratories. Specialized laboratories
national, regional and global levels. perform genotyping for any country, support WHO in
technical assistance and support drug resistance testing
The WHO HIVResNet HIV drug resistance laboratory when needed.
operational framework, originally published in 2017 (29),
described how designated HIVResNet Laboratory Network As of November 2022, the WHO HIVResNet Laboratory
laboratories functioned to support national, regional and Network includes 35 laboratories worldwide (Map 6),
global HIV drug resistance surveillance in a standardized 18 national laboratories, 10 regional laboratories, and
format according to WHO specifications. seven specialized laboratories. Fifteen laboratories have the
capacity for genotyping from dried blood spot specimens.
The WHO HIV drug resistance laboratory operational The monitoring framework for the Global Action Plan
framework was updated in 2020 (30) to reflect technical on HIV drug resistance 2017–2021 defined the research
and strategic developments, including consideration of and innovation indicator target as ≥70% of the regional
next-generation sequencing methods, updates to the and specialized laboratories have the capacity for HIV
standard operating procedures for post-testing quality drug resistance testing using dried blood spot specimens
assurance of HIV sequence data related to integrase and by 2021 (Annex 1). As of 2021, 76% of regional and
recommendations for assay validation. specialized laboratories have the capacity for HIV drug
resistance testing using dried blood spots, and this target
The third edition of the WHO manual for HIV drug was therefore achieved.
resistance testing using dried blood spots was
published in 2020 (31). It provides current best practice WHO is also advocating for increasing capacity within the
recommendations for laboratory HIV drug resistance WHO HIVResNet Laboratory Network to expand capacity
testing using dried blood spots. to test for integrase inhibitor resistance to support drug
resistance surveillance of people receiving a DTG-based
To expand the number of WHO-designated laboratories regimen. To date, 17 WHO HIVResNet Laboratory Network
for HIV drug resistance testing in low- and middle-income members have validated a genotypic assay for integrase
countries, WHO provided training, mentoring and capacity (Map 6), with several others expected to complete the
building of laboratory personnel, guidance on appropriate validations before the end of 2022.
HIV drug resistance testing standard procedures and quality
control. Also, WHO facilitated the participation of the
WHO-designated laboratories in a WHO-recognized external
quality assurance programme. Finally, WHO performed the
evaluation and designation process following the HIV drug
resistance laboratory operational framework.
 19

Map 6. WHO HIVResNet Laboratory Network, November 2022

20

7. PROGRESS ON BUILDING SUSTAINABLE

GOVERNANCE AND ENABLING MECHANISMS

© WHO/Blink Media - Nikolay Doychinov

STRATEGIC OBJECTIVE 5:
Ensure that governance and enabling mechanisms (advocacy, country ownership, coordinated
action and sustainable funding) are in place to support action on HIV drug resistance.
 21

7.1 Advocacy and awareness 7.2 Funding HIV drug resistance activities
Awareness of the HIV drug resistance burden among Establishing sustainable funding mechanisms is critical to
policy-makers, health-care workers, communities, support HIV drug resistance prevention and monitoring
patients and civil society is critical in combatting the activities in low- and middle-income countries. The action
emergence and spread of HIV drug resistance. The action framework of the Global Action Plan on HIV drug resistance
framework of the Global Action Plan on HIV drug resistance 2017–2021 encouraged global partners to mobilize funding
2017–2021 highlighted the need to effectively communicate to support strategies to prevent, respond to and monitor HIV
the importance of combatting HIV drug resistance with drug resistance at the global, national and local levels.
different audiences, to increase HIV drug resistance
awareness and commitment. The Global Action Plan on Global partners’ response
HIV drug resistance 2017–2021 stressed the need to build
The Global Fund to Fight AIDS, Tuberculosis and Malaria
community engagement and literacy for preventing and
and PEPFAR have committed to funding HIV drug resistance
responding to HIV drug resistance.
surveillance activities in countries. They have committed to
WHO’s response strengthening health-care systems and building laboratory
capacity to achieve universal viral load testing coverage.
WHO has been using avenues such as World Antimicrobial A review of Global Fund grants shows that, between 2015
Awareness Week (32) and Global Antimicrobial Resistance and 2017, 24 countries received support for HIV drug
and Use Surveillance System reports (33) for increased resistance prevention, monitoring and response, totalling
HIV drug resistance awareness and advocacy. In addition, about US$ 4.7 million. Most of this support funded HIV
WHO has developed infographics and video clips to simplify drug resistance surveys. Between 2018 and December 2021,
HIV drug resistance messaging, which are available on the 22 countries reported Global Fund support to implement
WHO HIV drug resistance website. 42 HIV drug resistance surveys.

Community organizations and civil society response In 2021–2022, PEPFAR supported the implementation of
laboratory-based surveys of acquired HIV drug resistance
In 2018, WHO, the Joep Lange Institute, Aidsfonds and surveillance in 16 countries.
the Partnership to Inspire, Transform and Connect the HIV
response (PITCH) met in The Hague, Netherlands, with Both the Global Fund and PEPFAR have committed to
civil society advocates, community representatives, health support countries to prevent and monitor the emergence of
practitioners, researchers and policy-makers to define the integrase inhibitor drug resistance as countries transition to
building blocks of a bold advocacy strategy to promote the DTG-based regimens as a means of ensuring the durability
implementation of the Global Action Plan (34). Overall, the of these regimens and as part of global efforts to end the
meeting affirmed the critical role of the community and AIDS epidemic as a public health threat by 2030.
civil rights groups in preventing and monitoring HIV drug
resistance and identified ways to engage them by:

• more strongly emphasizing that HIV drug resistance

is a quality-of-care concern that requires community
engagement to monitor and address;

• developing quality indicators and a framework to guide

community responses;

• increasing HIV drug resistance awareness by developing

simplified, evidence-informed messaging, including
coordinated audience-specific messaging at critical
events and through social media; and

• benchmarking countries and regions based on their

quality-of-care indicators to trigger community
engagement in supporting quality improvement
processes and stimulating advocacy actions.

In 2021, UNAIDS developed a guide for establishing

community-led monitoring of HIV services that countries
can leverage to implement the recommendations from the
meeting in The Hague (34, 35).
22

© Pan American Health Organization PAHO

7.3 Coordination, integration, alignment Fig. 2. WHO HIVResNet structure

and country ownership
The action framework of the Global Action Plan on HIV
drug resistance 2017–2021 highlighted WHO’s role in
ensuring continual dialogue between academia, country
programmes, policy-makers and donors on HIV drug
resistance. Also, countries were encouraged to develop
a five-year national action plan on HIV drug resistance,
with milestones and a funding plan, based on the Global
Action Plan on HIV drug resistance 2017–2021 and adapted
to the local context. Global partners were encouraged to
support the implementation of all elements of the Global
Action Plan on HIV drug resistance.

WHO’s response
• WHO HIVResNet. WHO has brought together
organizations and experts working in HIV drug
resistance to form WHO HIVResNet. It is a network
of international experts, including researchers,
laboratorians, implementing partners and members of
civil society, established in 2004 to support and provide
technical advice to WHO on activities to prevent,
monitor and respond to HIV drug resistance, optimize
the use of resistance testing and support policies
related to optimal ART selection (36). WHO HIVResNet
is governed by a Steering Group and organized into five
thematic working groups reporting to WHO (Fig. 2).
WHO meets with the working groups when needed and
annually convenes a meeting with all WHO HIVResNet
to promote the dialogue on HIV drug resistance
challenges and the progress to address them. The WHO
HIVResNet meeting reports are available at the WHO
HIV drug resistance website (36).
 23

• HIV drug resistance strategy. The WHO-recommended One core recommended activity was developing national
HIV drug resistance surveillance, monitoring and action plans on HIV drug resistance. The guidance
response strategy updated in 2021 articulated the core included how countries should develop and implement
set of WHO-recommended activities at the country level the national action plan on HIV drug resistance, who
to support programme planning and budgeting and should lead the process and a generic budget to develop
inform the preparation of grant proposals (Fig. 3). the national action plan on HIV drug resistance (22).

Fig. 3. HIV drug resistance strategy: recommended core set of activities in countries

• Country support to develop a five-year national The target established in the monitoring framework for
action plan on HIV drug resistance. From 2017 the Global Action Plan on HIV drug resistance 2017–2021
to 2021, WHO provided technical assistance to 17 (Annex 1) was 100% of 45 WHO focus countries reporting
countries to develop and review their national action data with HIV drug resistance strategy up to date by 2021.
plan on HIV drug resistance, including 12 in the African Therefore, this Global Action Plan on HIV drug resistance
Region, four in the Region of the Americas and one in 2017–2021 target was not achieved.
the Western Pacific Region.
Global partners’ response
Countries’ response
The Global Fund, United States Centers for Disease
Governance and ownership of HIV drug resistance Control and Prevention and other international partners
prevention, monitoring and response are critical elements provided financial and technical support for developing and
of a well-functioning ART programme. WHO recommends implementing national action plans on HIV drug resistance,
that countries integrate national action plans on HIV drug including updating ARV guidelines for HIV prevention and
resistance into their broader HIV response and plans to treatment, implementing HIV drug resistance surveys,
strengthen the public health sector. enhancing the quality of care, strengthening laboratory
systems to ensure quality-assured viral load testing and HIV
The number of WHO focus countries with a national drug resistance genotyping, analysing data and interpreting
action plan on HIV drug resistance ranged from 46% public health.
(13 of 28 focus countries reporting data to WHO) in
2018 to 64% (25 of 39 focus countries reporting data to
WHO) in 2020, suggesting in-country commitment and
multistakeholder engagement.
24

8. QUALITATIVE INFORMATION OBTAINED FROM

KEY STAKEHOLDER INTERVIEWS ABOUT
THE GLOBAL ACTION PLAN ON HIV DRUG
RESISTANCE 2017–2021

© WHO/Quinn Mattingly
 25

8.1 Qualitative interview methods HIV drug resistance surveillance

Individual and small-group semistructured interviews were Interviewees affirmed WHO’s pivotal role in developing
conducted with 62 key stakeholders from 36 institutions high-quality guidance for the surveillance monitoring
and 20 countries between March and June 2022 (Annex 2). of HIV drug resistance and the perceived impact of the
A background briefing note was prepared and circulated Global Action Plan on HIV drug resistance 2017–2021 on
before each interview. raising awareness of the need to implement nationally
representative HIV drug resistance surveys to inform the
The key stakeholder interviews were conducted with selection of optimal ART regimens. Specifically, the Global
the objective of understanding and documenting the Action Plan on HIV drug resistance 2017–2021 stimulated
perspectives of key stakeholders on: the implementation of pretreatment HIV drug resistance
surveys among adults and infants, with the results
• the utility, impact and challenges of the Global Action
supporting the accelerated global transition to DTG-based
Plan on HIV drug resistance 2017–2021 in preventing,
ART for all people living with HIV.
monitoring, and responding to HIV drug resistance;
Regarding future priorities, the consensus was that surveys
• the goals, structure and organization of a future global
of HIV drug resistance should continue, especially surveys
action plan 2023–2030; and
focused on HIV drug resistance among people experiencing
• an integrated global action plan on drug resistance for treatment failure while receiving DTG-based ART. Experts
HIV, viral hepatitis and sexually transmitted infections. noted that such surveys would be especially critical since
the prevalence of DTG resistance in populations failing
In addition to interviews, two virtual large-group discussions DTG-based ART in low- and middle-income countries
were conducted with viral hepatitis and sexually transmitted remains uncertain. However, interviewees commented on
infection content experts. The outcomes of the discussions the substantial time lag between survey implementation and
are summarized below. reporting, which lessens the impact of WHO-recommended
surveys on decision-making. This fundamental challenge
8.2 Interviewees’ perspectives: Global Action needs to be addressed in a future global action plan.
In addition, interviewees suggest that consideration be given
Plan on HIV drug resistance 2017-2021 to developing surveys using sentinel methods to complement
Key themes are described for each strategic objective. more extensive nationally representative surveys. Sentinel
Priority research questions identified by the interviewees to surveys could be designed with smaller sample sizes and
be addressed in a future global action plan are summarized. yield rapid, programmatically actionable information
on acquired DTG resistance in populations experiencing
HIV drug resistance prevention and response treatment failure.

Concerning the prevention of and response to HIV drug In addition, since an increasing number of countries perform
resistance, the consensus of the interviewees was that the HIV drug resistance testing for clinical management, there
Global Action Plan on HIV drug resistance 2017–2021 had was a consensus that guidance on responsibly aggregating
affected global HIV drug resistance prevention and response available deidentified person-level HIV drug resistance
during its lifespan. In particular, interviewees cited the value genotypes and demographic information could be used for
of the Global Action Plan on HIV drug resistance 2017–2021 programme decision-making. A framework would need to
in stimulating countries and implementing partners to use be developed to assess the quality, completeness, accuracy
HIV drug resistance surveys results in developing national and consistency of HIV drug resistance testing data obtained
and global normative guidance for using ARV drugs for during routine clinical care. Minimum criteria to define
HIV treatment and prevention. A clear and frequently cited populations could be developed, so the aggregate analysis
example of success was how the Global Action Plan on HIV would provide a cumulative and expanding understanding
drug resistance 2017–2021 catalysed the global dialogue of DTG drug resistance, including its prevalence, patterns
around the transition from NNRTI-based first-line ART to and determinants.
DTG-based ART. Data generated through the standardized
Leveraging next-generation sequencing infrastructure and
surveys documented increasing levels of NNRTI resistance
data sharing and reporting archetypes developed during the
in numerous countries and helped to propel the global shift
COVID-19 pandemic (Box 1) should be strongly considered
from NNRTI-based ART to DTG-based treatment. Between
in a future gap on HIV drug resistance and could facilitate
2014 and 2021, 21 surveys of pretreatment drug resistance
an enhanced and more timely global understanding of the
from 26 reported levels of resistance to nevirapine or
emerging prevalence and patterns of HIV drug resistance in
efavirenz exceeding 10%. By 2021, all 26 countries had
the DTG era. Greater use of next-generation sequencing for
initiated the transition to DTG-based first-line ART (15).
HIV drug resistance surveillance in the future may produce
In terms of future priorities, interviewees expressed the similar benefits for HIV programmes and global public health
view that WHO and partners should continue to conduct guidance as observed with SARS-CoV-2.
the important HIV drug resistance prevention and response
activities as they did in 2017–2021, with any adaptations that
may be needed in the era of tenofovir, lamivudine and DTG.
26

Box 1. The COVID-19 pandemic strengthened surveillance capacity

Concerning future WHO surveillance strategies, interviewees noted numerous examples of rapid genotyping,
reporting of results and data sharing for public health decision-making during the COVID-19 pandemic. There was
a consensus that the pandemic led to the expansion of next-generation sequencing capacity in several low- and
middle-income countries, which could be leveraged to strengthen future global HIV drug resistance surveillance
plans. Moreover, the COVID-19 pandemic accelerated the integration of genomics into public health, with the rapid
sequencing of the SARS-CoV-2 virus and evolving viruses with sequence information available in the public domain
within weeks for policy-makers to make decisions (37, 38).

In particular, interviewees noted that HIV drug resistance of the literature using the GRADE method, with targets
data are often slowly shared globally, if at all, and lessons established using a mixed-methods (normative and criterion
can be learned from other diseases and surveillance referencing) approach (40).
networks. The Global Initiative on Sharing Avian Influenza
Data (GISAID) Initiative is one such example. GISAID Although early warning indicators definitions have been
promotes the rapid sharing of data from all influenza recently updated to align with global strategic information
viruses and SARS-CoV-2 (39). Data sharing includes genetic guidance and targets have been adjusted, neither the
sequence and related clinical and epidemiological data targets nor the definitions have benefitted from a systematic
associated with human viruses and geographical and review focusing on populations receiving DTG-containing
species-specific data associated with avian and other regimens. Due to DTG’s high genetic barrier to the selection
animal viruses to help researchers understand how viruses of drug resistance–associated mutations, the early warning
evolve and spread during epidemics and pandemics (39). indicators definitions and targets established and validated
GISAID facilitates the rapid sharing of data by overcoming for NNRTI-based therapies in 2011 may no longer be
hurdles and restrictions that discourage or prevent sharing associated with population-level viral load suppression
of virological data before formal publication. The Initiative (HIV drug resistance prevention) or the emergence of
ensures free and open access to data within the GISAID possible HIV drug resistance (41, 42). Should WHO retain
platform for all individuals who agree to identify themselves early warning indicators of HIV drug resistance in the future,
and agree to uphold the GISAID sharing mechanism they would benefit from a similar revision as completed in
governed through its database access agreement (39). 2011. Also, the early warning indicators should be more fully
WHO and partners may learn from the key principles of integrated into routine monitoring and evaluation systems
GISAID in terms of full agreement of all GISAID partners to at the country level and more fully integrated into global
share data and publish data promptly while acknowledging normative guidance for strategic information and quality
the source of the data. of care. Finally, to realize their full potential, early warning
indicators should be accompanied by tool kits for action at
Monitoring early warning indicators of HIV the clinic and national programme levels to facilitate rapid
drug resistance data-informed intervention to optimize care.

Countries highly value the routine monitoring of early Research and innovation
warning indicators of HIV drug resistance because they
Overall, interviewees concurred that the Global Action Plan
collect facility-level information and document individual
on HIV drug resistance 2017–2021 had reliably given priority
clinic-level and overall HIV programme performance
to research questions at the time of its publication and that
in achieving quality service delivery over time and in a
the document helped to stimulate research into critical public
standardized and reproducible way. In addition, early
health and HIV programme–related HIV drug resistance
warning indicators provide simple, at-a-glance performance
questions. WHO’s convening role in establishing the research
strata, supporting local, district and national assessments
agenda was broadly acknowledged as necessary for future
and identifying areas of programmatic weakness that can
HIV drug resistance work. Some interviewees suggested that
be strengthened through appropriate local or national
WHO should guide development demonstration projects of
quality-of-care interventions.
new regimens (such as long-acting injectable PrEP) to ensure
Despite the overall positive consensus on the clinic and that critical public health questions related to HIV drug
programme-level value of routine early warning indicators resistance are embedded into these studies to the extent
monitoring, especially if integrated into overall quality possible. Such integration could enable more timely drug
improvement initiatives, interviewees queried whether resistance information and lead to more rapid and evidence-
early warning indicators of HIV drug resistance, as currently based recommendations on HIV drug resistance concerns.
defined, remained relevant in the era of DTG. Early warning Box 2 summarizes public health HIV drug resistance research
indicators of HIV drug resistance were introduced in 2006, questions identified during the interviews
with definitions revised in 2011 after a systematic review
 27

Box 2. HIV drug resistance research questions to be considered for inclusion in a future
global action plan on HIV drug resistance
HIV resistance to integrase inhibitors PrEP

• How quickly (if at all) will DTG resistance emerge • Is enhanced surveillance of HIV resistance to ARV
in populations experiencing treatment failure, drugs used for PrEP required?
and what are the epidemiological determinants of
DTG resistance in this context? • What role will oral or long-acting injectable PrEP
and PrEP roll-out have in potentially fuelling
• What are the population-level determinants of the population-level resistance?
emergence of integrase inhibitor resistance among
people for whom DTG-based ART is failing? HIV drug resistance testing

• What are the potential mechanisms of HIV resistance • What is the role of next-generation sequencing in
to integrase inhibitors? HIV drug resistance surveillance?

• Does the presence of DTG resistance always equate • When is HIV drug resistance testing in clinical
to clinical failure? practice for patient care most useful and necessary?

• What are the optimal ART regimens for use in the • What is the role of possible future point-of-care,
setting of DTG resistance in adults and children? or near point-of-care, integrase inhibitor drug
resistance testing?
Long-acting ARV drugs for HIV treatment
and prevention Other areas of work

• What is the potential impact of long-acting • What HIV drug resistance studies are needed
cabotegravir PrEP failure (and resistance selection) among children?
on subsequent DTG-based ART? • How should HIV drug resistance surveillance be
• Is the required enhanced surveillance of HIV drug given priority for key populations, adolescents and
resistance emergence during the drug tail period pregnant and breastfeeding women?
observed in long-acting ARV drug formulations? • Should the traditional concept of third-line and
• What is the role of modelling HIV drug resistance in salvage regimens be replaced by individual HIV
the era of integrase inhibitors, and what concerns drug resistance testing and individualized third-line
exist regarding cross-resistance to DTG among or salvage regimen composition?
people testing positive for HIV after receiving
long-acting cabotegravir PrEP?

• What is the optimal approach for resistance

monitoring and surveillance for new ARV drug
products, including long-acting formulations,
to be undertaken?

Laboratory capacity
The WHO HIVResNet Laboratory Network has been development of standardized platforms for cleaning and
successful in building sustained country capacity to monitor analysing HIV drug resistance genotypic data generated by
HIV drug resistance. Interviewees reported that the next-generation sequencing. Also, interviewees suggested
Global Action Plan on HIV drug resistance 2017–2021 was that WHO should emphasize the use of new technologies
effective and valued by stakeholders because it supported and stimulate the development of forward-thinking and
the ongoing establishment of a robust laboratory network novel ones. Additionally, special consideration could be given
providing high-quality HIV drug resistance test results for to developing and using high-throughput centralized regional
countries conducting national HIV drug resistance surveys. laboratories to improve efficiency and lower costs by testing
at scale. However, such a shift in approach may introduce
Looking to the future, some interviewees suggested a need new challenges for specimen transport, data ownership and
for WHO to clarify its designation criteria for laboratories timely reporting of results.
using next-generation sequencing and support the
28

Governance and enabling mechanisms 8.3 Interviewees’ perspectives: Global action

Stakeholders endorsed that the Global Action Plan on plan on HIV drug resistance 2023–2030
HIV drug resistance 2017–2021 delineated the tasks and
responsibilities of the stakeholders at different levels. The planning for a future global action plan on HIV drug
It facilitated narratives between stakeholders and donors, resistance 2023–2030 coincides with the global transition
informed regional and national plans for preventing and to DTG-based treatments and the rollout of long-acting ARV
monitoring HIV drug resistance and provided a framework drugs for treatment and prevention. Interviewees stated
for integrating HIV drug resistance plans into broader HIV that it would be necessary for WHO and partners to define
and health sector strategies. Notably, at the global level, the current key HIV drug resistance-related epidemiological
the Global Action Plan on HIV drug resistance 2017–2021 and public health questions, anticipate future questions
facilitated the integration of HIV drug resistance into the and identify optimal methods to answer them, whether by
broader context of prevention, treatment and care. research, surveillance or a hybrid of the two. In parallel,
For example, in 2021, WHO HIVResNet and the resistance WHO and WHO HIVResNet should review the lessons learned
agenda were integrated into the Conference on Antiretroviral from this landscaping review and evaluate lessons from
Therapy Optimization (CADO-4) and the Paediatric other WHO groups, such as the CADO and PADO groups and
Antiretroviral Drug Optimization (PADO-5) meetings. the WHO Enhanced Gonococcal Antimicrobial Surveillance
Programme (EGASP) in terms of structure, working
Interviewees reported that the structure of the five working modalities, reporting, governance and funding.
groups of the Global Action Plan on HIV drug resistance
2017–2021, one related to each strategic objective, was Many interviewees underscored the ongoing importance
complex and that the working group structure, scope and of adequate and sustained funding for HIV drug resistance
terms of reference need to be re-evaluated if they are monitoring and surveillance activities and future normative
to continue. One possible way to simplify the structure guidance development for supporting the WHO HIVResNet
would be to reorganize WHO HIVResNet along the lines Laboratory Network. To date, in-country surveys have been
of CADO and PADO – creating integrated adult, children mainly funded by donors, and countries have largely not
and adolescent working groups with cross-cutting content stepped up to incorporate the costs of implementing HIV
experts in each group to oversee the direction of future drug resistance surveys into national HIV care and treatment
strategic priority areas. budgets. Moreover, governments have often struggled to
incorporate funding for HIV drug resistance prevention,
In terms of governance at the secretariat level, one challenge surveillance and response activities into Global Fund and
articulated by interviewees was that WHO currently leads PEPFAR country and regional operating plans because of
all five workstreams and is insufficiently resourced to do so. competing priorities. PEPFAR and Global Fund remain major
Moreover, working groups are all voluntary and lack funding donors, and other sustainable modes of funding should be
to operationalize terms of reference. WHO may consider explored and secured in the future. Creative ways to engage
exploring whether new funding opportunities may emerge by national governments to set aside a percentage of their
assigning the responsibility for chairing some or all working national budget for resistance prevention, monitoring and
groups to other institutions, such as through designated response efforts must be realized. To facilitate the future
WHO collaborating centres on HIV drug resistance or through commitment of donors and implementing partners, they will
regional centres of excellence or partners. need to be involved in planning a future global action plan to
ensure that ongoing and new activities are funded. Finally,
Looking to the future, stakeholders endorsed a need for the concept of an integrated global action plan for HIV, viral
WHO to provide more frequent communication. There hepatitis and sexually transmitted infections may open new
was unanimous agreement that there should be greatly funding opportunities.
enhanced community partnerships and involvement of
people living with HIV and civil society in developing the
development of a future global action plan on HIV drug
resistance. In addition, community members should be
involved in developing global, regional and national HIV
drug resistance surveillance, monitoring and response plans
to give voice to community concerns, raise awareness of HIV
drug resistance and support the development of culturally
appropriate messaging around the links between quality
of care, viral load suppression at the population level and
preventing HIV drug resistance. Finally, all stakeholders
endorsed that comprehensive and inclusive consultations
will be required for a successful new global action plan on
HIV drug resistance.
 29

9. CONCLUSION
The goals of the Global Action Plan on HIV drug resistance In the next global action plan, it will be important to learn
2017–2021 were to articulate synergistic actions required from the feedback received from the broad consultative
to prevent HIV drug resistance from undermining efforts to process undertaken in this review of the Global Action Plan
achieve global targets on health and to ensure the ongoing on HIV drug resistance 2017–2021, consult with partners in
efficacy and durability of the available ARV drugs used for developing and designing the new global action plan and
prevention and for people living with HIV. Following review implement a robust monitoring and evaluation plan that
of progress in each of the five strategic objectives and starts with global action plan initiation, enabling WHO,
interviews with key stakeholders from 36 institutions and countries and other implementing partners to respond and
20 countries, the Global Action Plan on HIV drug resistance course correct.
has been largely successful in achieving these central goals,
even though specific indicator outcomes established in 2017 Given current global efforts to integrate health services
generally were not achieved. under the umbrella of universal health coverage, the
environment is conducive to development of a global action
Overall, the performance of programmatic quality plan unifying drug resistance for HIV, viral hepatitis and
indicators remained suboptimal in most countries reporting sexually transmitted infections. The success of a future
data during the period of the Global Action Plan on HIV global action plan unifying HIV, viral hepatitis and sexually
drug resistance 2017–2021, especially among children. transmitted infections will require robust and sustained
These findings underscore the need for proactive approaches public health surveillance, strong country engagement
to improving the quality of HIV treatment and care services and ownership, a willingness to share data in real time
to minimize the emergence of preventable drug-resistant and greatly enhanced community engagement in the
HIV. The reporting of indicator data from countries remains conceptualization and implementation.
suboptimal, underscoring a need to strengthen national
and regional data reporting systems for globally
relevant indicators.

The stakeholders interviewed endorsed that the Global

Action Plan on HIV drug resistance 2017–2021 clearly
delineated the tasks and responsibilities of the stakeholders,
facilitated narratives with stakeholders and donors and
informed regional and national plan development. Notably,
the Global Action Plan on HIV drug resistance 2017–2021
facilitated the integration of HIV drug resistance into the
broader context of prevention, treatment and care, especially
more recently in 2021 with the inclusion of WHO HIVResNet
in CADO-4 and PADO-5 meetings.
30

REFERENCES
1. World Health Organization. Antimicrobial resistance key facts. 11. Billong SC, Fokam J, Penda CI, Mvilongo EA, Fodjo R,
2021 (https://www.who.int/news-room/fact-sheets/detail/ Messeh A et al. Profil national des indicateurs d’alerte
antimicrobial-resistance, accessed 28 November 2022). precoce de la pharmaco-resistance du VIH au Cameroun.
[National profile of early warning indicators of HIV
2. World Health Organization. Global action plan on HIV pharmaco-resistance in Cameroon]. Pan Afr Med J.
drug resistance 2017–2021. 2017 (https://apps.who.int/iris/ 2020;37:374. doi: 10.11604/pamj.2020.37.374.17649.
bitstream/handle/10665/255883/9789241512848-eng.pdf,
accessed 28 November 2022). 12. Getaneh Y, Zealyas K, Adugna F, Kursha K, Atsbeha GE,
Kassa D et al. HIV drug resistance early warning indicators
3. World Health Organization. Global action plan on antimicrobial in Ethiopia: Variability at regional and health facility levels
resistance. 2016 (https://www.who.int/publications/i/ and trend over time. Int J Infect Dis. 2020;95:90-7. doi:
item/9789241509763, accessed 28 November 2022). 10.1016/j.ijid.2020.02.031.
4. Global health sector strategy on HIV: 2016-2021 Towards 13. Marume A, Zikiti A, Chapoterera B, Maradzika J. Evaluation
ending AIDS. 2016 (https://www.who.int/publications/i/ of the early warning indicators of HIV
item/WHO-HIV-2016.05, accessed 28 November 2022). drug resistance surveillance system in Manicaland
province, Zimbabwe. Afr J AIDS Res. 2019;18:123-9.
5. World Health Organization. Global Report on Early
doi: 10.2989/16085906.2019.1621359.
Warning Indicators of HIV Drug Resistance: Technical
Report, July 2016. (https://apps.who.int/iris/bitstream/ha 14. Phillips AN, Stover J, Cambiano V, Nakagawa F, Jordan MR,
ndle/10665/246219/9789241511179-eng.pdf, accessed 28 Pillay D et al. Impact of HIV Drug Resistance on HIV/AIDS-
November 2022). Associated Mortality, New Infections, and Antiretroviral
Therapy Program Costs in Sub-Saharan Africa. J Infect Dis.
6. World Health Organization. Maintaining and improving
2017;215:1362-5. doi: 10.1093/infdis/jix089.
quality of care within HIV clinical services. 2019 (https://
apps.who.int/iris/handle/10665/325857, accessed 28 15. World Health Organization. Guidelines on the public
November 2022). health response to pretreatment HIV drug resistance
July 2017. (https://apps.who.int/iris/bitstream/hand
7. Project ECHO | The University of New Mexico. A Glance
le/10665/255880/9789241550055-eng.pdf?sequence=1,
at Quality Assurance and Quality Improvement (QA/QI)
last accessed 28 November 2022).
Practices. 2019 (https://hsc.unm.edu/echo/partner-portal/
echos-initiatives/who-collaborations/who-hiv-care-services. 16. World Health Organization. Consolidated guidelines
html, accessed 28 November 2022). on HIV prevention, testing, treatment, service delivery
and monitoring: recommendations for a public health
8. World Health Organization. Differentiated Technical
approach. 2021 (https://www.who.int/publications/i/
Support. Managing technical support to drive impact
item/9789240031593, accessed 28 November 2022).
on HIV and viral hepatitis. Focus Countries 2018-2019.
Unpublished internal guidance. 17. World Health Organization. HIV drug resistance
The 45 WHO Focus Countries with High HIV Burden are: report 2021 (https://www.who.int/publications/i/
Tier 1 (over 60% of global disease burden): Cameroon, item/9789240038608, accessed 28 November 2022).
Democratic Republic of the Congo, India, Indonesia, Kenya,
Mozambique, Nigeria, Pakistan, Philippines, Russian 18. World Health Organization. HIV drug resistance
Federation, South Africa, United Republic of Tanzania, surveillance in countries scaling up pre-exposure
Uganda, Zambia, Zimbabwe. prophylaxis. 2020 (https://www.who.int/publications/i/
Tier 2 (additional 20-30% of global disease burden): item/9789240009813, accessed 28 November 2022).
Angola, Botswana, Brazil, Cambodia, Chad, China, Côte
d’Ivoire, Dominican Republic, Eswatini, Ethiopia, Ghana, 19. World Health Organization. Laboratory-based survey of
Guatemala, Islamic Republic of Iran, Jamaica, Lesotho, acquired HIV drug resistance using remnant viral load
Malawi, Malaysia, Mali, Mexico, Morocco, Myanmar, specimens. 2021 (https://www.who.int/publications/i/
Namibia, Papua New Guinea, Somalia, Sudan, South item/9789240025417, accessed 28 November 2022).
Sudan, Thailand, Ukraine, Viet Nam. 20. World Health Organization. Clinic-based survey of
9. UNAIDS Global AIDS Monitoring (https://www. acquired HIV drug resistance. 2021 (https://www.who.
unaids.org/en/global-aids-monitoring, accessed 28 int/publications/i/item/9789240035003, accessed 28
November 2022). November 2022).

10. Asio J, Watera C, Namuwenge N, Kirungi W, Musinguzi 21. World Health Organization. Sentinel surveys of acquired
J, Mugagga K et al. Population-based monitoring of HIV resistance to dolutegravir among people receiving
HIV drug resistance early warning indicators in Uganda: dolutegravir-containing antiretroviral therapy. 2022
A nationally representative survey following revised (https://www.who.int/publications/i/item/9789240063204,
WHO recommendations. PLoS One. 2020;15:e0230451. accessed 28 November 2022).
doi:10.1371/journal.pone.0230451.
 31

22. World Health Organization. HIV Drug Resistance Strategy, 34. Netherlands Ministry of Foreign Affairs. Summary report:
2021 Update. (https://www.who.int/publications/i/ HIV Drug Resistance: Advocacy Strategy Meeting. 2018
item/9789240030565, accessed 28 November 2022). (https://www.joeplangeinstitute.org/wp-content/
uploads/2018/07/HIVDR-Advocacy-Strategy-meeting-
23. World Health Organization. HIV drug resistance report summary-report.pdf, accessed 28 November 2022).
2017 (https://apps.who.int/iris/bitstream/hand
le/10665/255896/9789241512831-eng.pdf, accessed 28 35. UNAIDS. Establishing community-led monitoring of HIV
November 2022). services. 2021 (https://www.unaids.org/sites/default/files/
media_asset/establishing-community-led-monitoring-hiv-
24. World Health Organization. HIV drug resistance report services_en.pdf, accessed 28 November 2022).
2019 (https://www.who.int/publications/i/item/WHO-CDS-
HIV-19.21, accessed 28 November 2022). 36. World Health Organization. HIVResNet. 2022 (https://www.
who.int/groups/who-hivresnet, accessed 28 November 2022).
25. World Health Organization. Consolidated HIV strategic
information guidelines: driving impact through programme 37. Scheepers C, Everatt J, Amoako DG, Tegally H, Wibmer CK,
monitoring and management. 2020 (https://www.who. Mnguni A et al. Emergence and phenotypic characterization
int/publications/i/item/9789240000735, accessed 28 of the global SARS-CoV-2 C.1.2 lineage. Nat Commun.
November 2022). 2022;13:1976. doi: 10.1038/s41467-022-29579-9.

26. World Health Organization. Technical update: 38. E. Wilkinson, M. Giovanetti, H. Tegally, J. E. San,
considerations for developing a monitoring and evaluation R. Lessells, D. Cuadros, et al. A year of genomic surveillance
framework for viral load testing: collecting and using data reveals how the SARS-CoV-2 pandemic unfolded in Africa
for scale-up and outcomes. 2019 (https://apps.who.int/iris/ Science 2021 Vol. 374 Issue 6566 DOI: 10.1126/science.
handle/10665/324745, accessed 28 November 2022). abj4336 (https://www.science.org/doi/10.1126/science.
abj4336, accessed 28 November 2022).
27. World Health Organization. Toolkit: HIV molecular
diagnostics toolkit to improve access to viral load testing 39. The Global Initiative on Sharing Avian Influenza Data.
and infant diagnosis: HIV treatment and care. 2019 GISAID: Enabling rapid and open access to epidemic
(https://apps.who.int/iris/handle/10665/325961, and pandemic virus data. 2022 (https://gisaid.org/about-
accessed 28 November 2022). us/mission/, accessed 28 November 2022).

28. World Health Organization. Module for assessing and 40. Meeting report on assessment of World Health Organization
strengthening the quality of viral load testing data within HIV drug resistance early warning indicators. Geneva:
HIV programmes and patient monitoring systems. 2020 World Health Organization; 2012 (https://apps.who.int/iris/
(https://www.who.int/publications/i/item/978-92-4- handle/10665/75186, accessed 28 November 2022).
001037-6, accessed 28 November 2022).
41. Jonas A, Sumbi V, Mwinga S, DeKlerk M, Tjituka F, Penney
29. World Health Organization. WHO/HIVResNet HIV drug S et al. HIV drug resistance early warning indicators
resistance laboratory operational framework. 2017 in namibia with updated World Health Organization
(https://www.aidsdatahub.org/sites/default/files/resource/ guidance. PLoS One. 2014;9:e100539. doi: 10.1371/journal.
who-hivresnet-hiv-drug-resistance-laboratory-operational- pone.0100539.
framework-2017.pdf, accessed 28 November 2022).
42. St-Jean M, Harrigan PR, Sereda P, Montaner J, Lima VD.
30. World Health Organization. WHO HIVResNet HIV drug An assessment of the relationship between the World
resistance laboratory operational framework Second Health Organization HIV drug resistance early warning
edition. 2020 (https://www.who.int/publications/i/ indicators and HIV drug resistance acquisition. HIV Med.
item/978-92-4-000987-5, accessed 28 November 2022). 2017;18:342-53. doi: 10.1111/hiv.12435.

31. World Health Organization. WHO manual for HIV drug

resistance testing using dried blood spot specimens
Third edition. 2020 (https://www.who.int/publications/i/
item/9789240009424, accessed 28 November 2022).

32. World Health Organization. World Antimicrobial Awareness

Week. 2019 (https://www.who.int/campaigns/world-
antimicrobial-awareness-week, accessed 28 November 2022).

33. World Health Organization. Global antimicrobial resistance

and use surveillance system (GLASS) report: 2022
(https://www.who.int/publications/i/item/9789240062702,
accessed 28 November 2022).
32

ANNEX 1. MONITORING FRAMEWORK AND

OUTCOMES FOR THE GLOBAL ACTION PLAN ON
HIV DRUG RESISTANCE 2017–2021
Areas of work 2021 indicator target 2021 indicator outcome
1. Prevention ARV drug stock-outs <15% of countries reporting any ARV drug stock-out during Adults: 50% (13 of 26)
and response a 12-month period (among the 45 WHO focus countries
reporting data) Children: 50% (13 of 26)

Retention on ARTa >90% of countries reporting >85% retention on treatment at Adults: 29% (6 of 21)
a defined time point (among the 45 WHO focus countries
reporting data) Children: 43% (6 of 14)

Viral load testing ≥50% of countries achieving ≥70% viral load coverage: people Adults: 40% (10 of 25)
coverage receiving ART having a 12-month viral load test result available
in their medical record (among the 45 WHO focus countries Children: 77% (10 of 13)
reporting data)
Viral load suppression ≥90% of countries reporting viral load suppression of ≥90% Adults: 78% (7 of 9)
among people receiving ART with a viral load test result available
(among the 45 WHO focus countries reporting data) Children: 25% (2 of 8)

Use of second-line ≥80% of countries report having at least 5% of people Adults: 45% (13 of 29)
ART regimens receiving second-line ART (among the 45 WHO focus countries
reporting data) Children: 74% (20 of 27)

National response to 100% of countries responding to HIV drug resistance through Adults: 100% (26 of 26)b
HIV drug resistance programme adjustments and/or revising national ART guidelines
Children: 100% (11 of 11)c

2. Monitoring Surveillance 100% of countries conducting and reporting on HIV drug 57% (12 of 21)
and surveillance resistance surveillance (among the 45 WHO focus countries
reporting data in the last 3 years)
Early warning indicators ≥90% of countries assessing early warning indicators for HIV 21% (6 of 28)
relevant for HIV drug drug resistance at a clinic-level (among the 45 WHO focus countries)
resistance
Global report on HIV Two WHO reports published by 2021 Three WHO reports published in
drug resistance 2017, 2019 and 2021
3. Research and Implementation of One position paper on priority HIV drug resistance research Research questions published
innovation HIV drug resistance-– questions in the 2018 Global Action
related research Plan report
established in the
Global Action Plan on ≥50% of research questions defined in the Global Action Plan 92% (22 of 24) of the HIV drug
HIV drug resistance have been planned or initiated resistance research questions
identified are being addressed
4. Laboratory Expansion of HIV drug ≥70% of WHO HIVResNet regional and specialized labs 76% (13 of 17) of regional and
capacity resistance testing designated for HIV drug resistance using DBS specialized laboratories with
laboratories the capacity for DBS testing
5. Governance Mobilization of 100% of WHO HIV focus countries including HIV drug resistance Data unavailable
and enabling resources to implement activities in funding proposals to Global Fund and PEPFAR,
mechanism the Global Action Plan other sources or country health budgets
Mobilization of 100% of WHO HIV focus countries having 100% budget for HIV Data unavailable
resources to coordinate, drug resistance activities
monitor and support
the Global Action Plan’s
implementation
National HIV drug 100% of countries with HIV drug resistance strategy up to date 64% (23 of 36)
resistance strategy (among the 45 WHO focus countries reporting data)

a
Represents 2018 data. From 2019 onwards, the retention indicator was revised to “total attrition on ART”, which has since then been incorporated into WHO’s
indicator guidance and monitoring tools, but countries had not yet started reporting by the end of 2021.
b
Countries that reported to WHO having pretreatment drug resistance to non-nucleoside reverse transcriptase inhibitors of ≥10%.
c
Countries that reported to WHO data on HIV drug resistance survey among infants <18 months.
Data sources: Global AIDS Monitoring, WHO surveys, reports received from countries and Global Fund and PEPFAR reports.
 33

ANNEX 2. WHO AND PARTNER ORGANIZATIONS

INTERVIEWED, BY WHO REGION
Institution WHO region
WHO headquarters Headquarters

WHO regional offices African Region, Region of the Americas, South-

East Asia Region, European Region, Eastern
Mediterranean Region, Western Pacific Region

WHO HIVResNet Steering Group chairs African Region, Region of the Americas,
Western Pacific Region

WHO HIVResNet working group co-chairs African Region, Region of the Americas,
European Region

WHO HIVResNet Laboratory Network African Region, Region of the Americas

National Health Laboratory Service, South Africa African Region

Ministry of Health, Kenya African Region

Ministry of Health, Uganda African Region

Wits Reproductive Health and HIV Institute, University of Witwatersrand African Region

HIV treatment advocates network (AfroCab) African Region

International Treatment Preparedness Coalition African Region

Ministry of Health, Uganda African Region

Global Fund to Fight HIV, Tuberculosis and Malaria European Region

National Haemophilia Center, Israel European Region

French National Institute of Health and Medical Research (Inserm) European Region

Institute for AIDS Research (IrsiCaixa), Spain European Region

University College London European Region

Partners in Health Region of the Americas

United States Centers for Disease Control and Prevention Region of the Americas

United States Agency for International Development Region of the Americas

Johns Hopkins University Region of the Americas

Columbia university Region of the Americas

University of California, San Francisco Region of the Americas

University of California, Los Angeles Region of the Americas

Harvard University Region of the Americas

University of Pittsburgh Region of the Americas

Oswaldo Cruz Foundation (Fiocruz), Brazil Region of the Americas

Data First Consulting Region of the Americas

AIDS Healthcare Foundation Region of the Americas

Elizabeth Glaser Pediatric AIDS Foundation Region of the Americas

Chennai Antiviral Research and Treatment South-East Asia Region

For more information, contact:

World Health Organization

Department of HIV/AIDS
20, avenue Appia
1211 Geneva 27
Switzerland

E-mail: [email protected]

www.who.int/hiv