Kuwait university

Faculty of pharmacy
Department of pharmacology and therapeutics

Human immunodeficiency virus case

Done by:
Maraheb Nasser Atyah 2171113392
Fatemah Soud Al-Aradah 2171113538
Maryam Waleed Al-Yosef 2171113698
Nojoud Tareeq Al-Furaih 2171113946
 Dr. Omamah alfarisi
Human immunodeficiency virus : Case Study

1.a. What subjective and objective information indicates the presence of HIV/AIDS

Subjective:

The patient has Sore throat, myalgia, and malaise.she also complained of vomiting,

watery diarrhea and fever that has been felt in the 5 days (T=39.7C).

Objective:

• erythema in the posterior oropharynx

• enlargement in the posterior ocular lymph nodes

• decreased white blood cells (WBC count 2.6 x 10^3 cells/mL)

• HIV viral load level > 10 million copies/mL of HIV RNA

• CD4+ cell count of 121 cells/mL

• Positive ocular cytomegalovirus

• HIV mRNA (> 10 million copies/mL)

 1.b. Assess the severity of HIV/AIDS based on the subjective and objective information

available.

2014 CDC Case Definition for HIV Infection Adolescents and Adult Staging System is

commonly used for determining the stage of AIDS. In this staging system, there are three stages,

described in Figure 1. Assessment of the severity of HIV infection based on CD4+ cell count or

documentation of AIDS-defining condition. The patient is diagnosed with stage 3 according to

CDC guideline. This is because she had CD4+ count less than 200/mm^3, as well

as she has AIDS defining conditions (cytomegalovirus retinitis) that increase the severity of

HIV/AIDS.

1. Viral transmission phase:

- At this stage, the level of CD4 cell count is high and the virus level is low (below detection

levels).

- Usually, there is no symptoms.

 2. Acute phase (primary):

- The virus level starts to increase acutely and sharply.

- At the same time, CD4 levels goes down acutely and sharply as well.

- Some patients might experience flu like symptoms and many remain asymptomatic.

- Blood test shows: low CD4 cell count levels (but not <200) and high HIV virus levels.

3. Chronic phase without AIDS: (months to years)

- The body now is recognizing the virus, so it's trying to fight the virus and produce more CD4.

- Therefore, the number of CD4 cells start to increase again and the viral load decrease.

- There will be a point where there will a balance between levels of CD4 and viral load.

- The patient usually doesn't experience symptoms in this phase.

- But still even during this stable phase, the body is fighting the virus and the virus is still trying to

infect more of the CD4 cells.

- After some time, CD4 will collapse eventually and will go really down.

- If it goes less than 200, the patient will start experiencing AIDS symptoms and viral load wil

sharply increase in that period.

1.c. What additional information is needed to fully assess this patient’s HIV/AIDS?

HIV is diagnosed through a multi-step process. The presence of HIV infection is screened

with a multiple test such as:

• Urinalysis: to detect if there is AIDS defining condition related to UTI

• Complete blood cell count (CBC)

• Complete metabolic and lipid profile

• Hepatic and renal function test before medication initiation

• Tropism testing: if consider CCR5 antagonist (Maraviroc)

• HLA-B*5701 test: if consider (abacavir)

• Drug resistance testing

• Test for sexually transmitted test: syphilis, chlamydia and gonorrhea.

• Hepatitis A, B, and C

• Screen for osteoporosis.

• Vaccines:

- COVID-19: all HIV patients should receive COVID-19 vaccine regardless of their HIV viral load

or CD4 T lymphocyte.

2.a. Create a list of the patient’s HIV-related drug therapy problems and prioritize them. Include

assessment of medication appropriateness, effectiveness, safety, and patient adherence.

1. AIDS: considering the viral mRNA was greater than 10 million copies per milliliter, and she

tested positive for ocular cytomegalovirus, she is stage 3 aids because the CD4 counts were 121

cells/mm^3( less than 200 cells/mm^3) and 9.4% and she have aids defining condition, yet not

treated ( indication: needs additional therapy: untreated condition ).

2. Ocular Cytomegalovirus: Patient tested positive for ocular cytomegalovirus as a complication of

aids, but was not treated despite developing erythema in the posterior oropharynx, enlargement
 in the posterior ocular lymph nodes, decreased visual acuity and blurred vision, and testing

positive for ocular cytomegalovirus, yet not treated (indication: needs additional therapy:

untreated condition ).

3. Chronic kidney disease: patient GFR = 36 ml/min which is stage 3b ( indication: needs additional

therapy: untreated condition ).

4. Marijuana : patient stated that she smoke marijuana (cannabis) occasionally, and since cannabis

has not been found to have a negative effect on patients capacity to achieve viral suppression or

adherence to ART, however in the absence of sufficient information, cannabis use

among hiv patients should be discouraged ( indication : unnecessary drug therapy: addictive).

Patient uses promethazine without indication for its use , however promethazine and

marijuana interact with each other, Combining promethazine and cannabis may worsen

negative effects, such as lightheadedness, tiredness, disorientation, and trouble focusing. a

few persons,especially the old, may also endure deterioration in their motor, cognitive, and

judgment skills, and motor coordination. ( safety: adverse drug reaction: unsafe drug use ).

5. Immunization : patient immunization records is missing, so we will ask about all the

previous vaccines and the patient any missing vaccines ( indication: additional drug

therapy: preventive / prophylactic).

6. Others : Patient uses second-generation antihistamine Ranitidine in addition to first-

generation antihistamine Promethazine, but there are no signs or symptoms that point to

allergies or ulcers ( indication: unnecessary drug therapy: no indication).

Although it is a very uncommon side effect, taking fluconazole and promethazine together can

increase the chance of an abnormal heart rhythm, which might be dangerous and even

fatal. ( safety: adverse drug reaction: drug interaction).

2.b. What are the goals of pharmacotherapy for the patient’s HIV-related drug therapy problems?

Goals of antiretroviral therapy are to :

• Maximally and durably suppress plasma HIV RNA

• Restore and preserve immunologic function

• Reduce HIV-associated morbidity and prolong the

duration and quality of survival

• Prevent HIV transmission.

2.c What are the possible pharmacotherapeutic options that are available for treating her HIV?

Since patient has GFR = 36 ml/min and newly diagnosed

1. Tenofovir alafenamide (TAF) + emitrictabine (FTC) or lamivudine (3TC)

+ dolutegravir (DTG)

2. Tenofovir alafenamide (TAF) + emitrictabine (FTC) + bictegravir (BIC)

3. Tenofovir alafenamide (TAF) + emitrictabine (FTC) or lamivudine (3TC) + ritonavir-

boosted darunavir

4. Abacavir (ABC) + lamivudine (3TC) + dolutegravir (DTG)

3.a. Create an individualized, patient-centered, team-based care plan to optimize medication

therapy for the patient’s HIV-related drug therapy problems. Include specific drugs,

dosage forms, schedules and duration of therapy.

 For our patients, systemic antiretroviral drugs (ART) is recommended to reduce morbidity,

mortality, and to prevent the transmission of HIV to others. Also, it should be started

immediately due to the presence of AIDS defining illness

(cytomegalovirus retinitis), and CD4+ counts below 200 cell/mm*3.

The recommended regimen for our treatment-naïve patient with moderate reduced

kidney function as her eGFR = 36 mL/min/1.73m*2 :

o Tenofovir (TAF) / emtricitabine (FTC) -containing regimen, both are considered nucleoside

reverse transcriptase inhibitors (NRTIs). The preferred regimen is:

➢ 2 NRTIs + 1 INSTIs (Integrase strand transfer inhibitors)

▪ Tenofovir (TAF) + Emtricitabine (FTC) + Bictegravir (BIC)

o Tenofovir alafenamide (TAF) is preferred over tenofovir disproxil fumarate (TDF) as its equally

effective, less nephrotoxic, and has less effect on bone density.

o Emtricitabine (FTC) and Lamivudine (3TC) are both clinically equivalent, highly well tolerated,

and have minimal rare side effects profile.

o Lamivudine (3TC) requires dose adjustment if eGFR<50 mL/min/1.72m*2, therefore not

chosen here.

o Bictegravir (BIC) is preferred over Dolutegravir (DTG) as it has lower rate of central nervous

system side effects (e.g; insomnia, headache).

According to Lexicomp 30th edition, each taken separately.

✓ TAF: One 25mg tablet once daily + FTC: One 200mg capsule once daily +

BIC: One 50mg tablet once daily, lifelong.

✓ Or Biktarvy, a drug with a fixed dose combination of 25mg TAF, 200mg FTC, and 50mg BID,

once daily for life.

3.b. What consideration should you take into account for choosing her initial ART regimen?

To determine which ART regimen is the best for her, we have to take into account the

following:

1. Comorbid conditions (e.g; our patient has renal insufficiency with eGFR=36 mL/min/1.73 m*2),

for that TDF was removed from her regimen as it cause kidney injury. Moreover, Atazanavir; a

protease inhibitors is associated with development of renal stones and kidney injury is

contraindicated.

2. Pregnancy, Raltegravir (RAL) is the preferred regimen. BIS

& DTG are contraindicated according to FDA released safety alert in 2018 that it increase rate of

neural tube defects in infants. Cobicistat-boosted containing regimen she be avoided due to

decreased drug levels during pregnancy.

3. HLA-B*5701 testing for Abacavir, as abacavir (ABC) + Lamivudine (3TC)

= Dolutegravir (DTG) is another regimen that can be used if the test was negative.

4. Especially for our patient, drug resistance testing using an HIV genotype test for mutations

in Integrase (e.g; BIC).

3.c. Discuss the role of HIV resistance testing in designing a regimen for anti- retroviral

treatment-naïve patients.
 Drug resistance is caused by changes in the genetic structure of HIV that affect the

ability of medication to block the replication on the virus which eventually causes HIV

treatment failure. There are 2 types of resistance, primary and secondary

resistance. Primary resistance happens when a person obtain a strain of HIV that is already

resistant to certain antiretroviral drugs. Whereas secondary resistance, happens during HIV

treatment. That’s why it’s recommended new regimens should include at least two and

preferably three fully active agent to avoid resistance.

For treatment-naïve patients, HIV drug-resistance testing is recommended at entry into

care for people with HIV to guide the selection for the best initial antiretroviral (ARV)

regimen, and to avoid what is not. Resistance testing is a laboratory testing by using a

sample of a blood. There are 2 types of testing; Genotype and Phenotype.

Genotypic testing detects specific drug-resistance mutation in relevant viral genes. This

testing requires a plasma viral load of at least 500 to 1000 copies/mL. It mostly

involve testing for mutations in the reverse transcriptase,

protease, and Integrase genes of circulating RNA in plasma to detect mutations that are

known to cause drug resistance. It is preferred over phenotype for ARV-naïve patients due

to:

1. Lower cost.

2. Rapid results within 1-2 weeks.

3. Greater sensitivity for detecting mixtures of wild type and resistant virus.
4. Less complicated.

Phenotypic testing measures the ability of a virus to grow in different concentration of

ARV drugs. Replication of these viruses at different drug concentrations is monitored by

expression of a reporter gene and is compared with replication of a reference HIV

strain.Useful in patient who have viral infection with multiple resistance mutation with

different impact on antiviral drugs. Disadvantages are that the results take longer time 2-3

week, more complicated, and high cost.

Limitations of both genotype and phenotype tests include:

1. Lack of uniform quality assurance testing.

2. Relatively high cost.

3. Insensitivity to minor viral species.

HIV drug-resistance testing is not recommended after discontinuing a drug because the

percentage of drug-resistant may decrease considerably in the absence of the drug. It

should be done while a person is taking the drugs, or if this is not possible, then within 4

weeks of stopping therapy.

HIV drug-resistance testing is required depending on viral load levels:

 .

4.a. What clinical and laboratory parameters are necessary to evaluate the clinical efficacy and

toxicity of the antiretroviral regimen selected? Specify the frequency with which you will

monitor these parameters. Indicate therapeutic goal.

I. Clinical parameters include: Subjective and objective measures at follow-up visits can be used to

evaluate signs and symptoms of improvement, as well as resolution, decreased frequency or

reduction in the severity of HIV-associated illness. Improvement in the overall well-being and

functional status of the patient, restore immune function, and improve overall health can all be

used to monitor treatment success.

II. Laboratory parameters include:

Frequency of Testing
 Laboratory Tests Entry ART After 4- 8 Every 3 Every 6 Every 12 Treatment

Into initiation weeks months months months Failure

Care

HIV-RNA ✔️ ✔️ ✔️ ✔️ ✔️ ✔️ ✔️

CD4 ✔️ ✔️ - ✔️ ✔️ ✔️ ✔️

Genotypic ✔️ ✔️ - - - - ✔️

Resistance

Hepatitis B ✔️ ✔️ - - - - -

LFT ✔️ ✔️ ✔️ - ✔️ - -

Differential CBC ✔️ ✔️ - ✔️ ✔️ ✔️ -

Lipid Profile ✔️ - - - - ✔️ -

Random/ Fasting ✔️ ✔️ - - - - ✔️

Glucose

Urinalysis ✔️ - - - - - -

PregnancyTest ✔️ ✔️ - - - - -

III. Therapeutic goal:

• Maximally and durably suppress plasma HIV-RNA.

• Restore and preserve immunologic function.

• Reduce HIV-associated morbidity and prolong the duration and quality of survival.

• Minimize opportunistic infections associated with HIV.

• Prevent HIV transmission.

4.b. When will you measure her viral load next?

Within 4 to 8 weeks after treatment initiation to confirm an adequate

virologicresponse to ART, indicating appropriate regimen selection and patient adherence

to therapy.

4.c. What important information would you provide to the patient about her therapy?

 Provide the patient with a brief overview of HIV infection and possible

treatmentsavailable.

 Explain to the patient the benefits of starting ART and the necessity of

taking hermedications as prescribed.

 Educate the patient on how to take her medications according to her individual regimen

and any potential side effects she may experience.

 If patient developed clinical or laboratory findings suggestive of lactic acidosis or

pronounced hepatotoxicity, treatment should be suspended.

 Monitor serum phosphors in patient with chronic kidney disease.

 Patient should inform her doctor if she experienced skin discoloration, diarrhea, nausea,

or headache.

 Give the patient emotional and social support because adherence is influenced by these

factors.
  Provide risk reduction counseling to avoid HIV transmission between partners who share

needles or engage in sexual activity.

 Patient should be informed that transmission is possible during periods of poor adherence

or treatment interruption.

References

DiPiro, J. T. (2020). Pharmacotherapy: A pathophysiologic approach. McGraw Hill.

Drug interaction list: Promethazine, cannabis, vancomycin. Drugs.com. (n.d.). Retrieved November 9,

2022, from https://www.drugs.com/interaction/list/?drug_list=1949-0%2C2758-0%2C2289-0

Information on HIV/AIDS treatment, prevention and research: NIH. Clinicalinfo. (n.d.).

Retrieved November 9, 2022, from https://clinicalinfo.hiv.gov/

Laboratory testing for initial assessment and monitoring of people with HIV receiving

antiretroviral therapy. NIH. (n.d.). Retrieved November 9, 2022, from

https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/

tests-initial-assessment-and-follow-full