HIV Antiretroviral Drugs Quiz

HIV Care and Prevention

• Presenter: Dr. Debbie Kelly, PharmD, FCSHP, AAHIVP, Professor, Memorial University, Clinical Pharmacotherapy Specialist, Provincial HIV program
• Date: Winter 2025

Learning Objectives

• Describe the global and national epidemiology of HIV
• Discuss Canada's public health goals for HIV
• Outline who, how, and when to test for HIV infection
• Describe the treatment goals and principles of HIV treatment, relating to antiretroviral (ARV) therapy
• Explain monitoring ARV therapy for effectiveness and safety
• Discuss the epidemiology of opportunistic infections (OIs) in the context of HIV
• Detail recognition and diagnosis of major OIs (e.g., P. jirovecii pneumonia) in a patient with HIV infection
• Cover the management approach for P. jirovecii pneumonia, including treatment and follow-up
• Describe HIV prevention and control methods

Definitions and Terminology

• HIV: Human Immunodeficiency Virus, responsible for AIDS
• AIDS: Acquired Immunodeficiency Syndrome; CDC definition based on CD4 count ( <200) or CD4 count (>200) and AIDS-indicator conditions
• ARV: Antiretroviral therapy; medications to treat HIV infection, always combination therapy
• Opportunistic Infection (OI): Infection in an immunocompromised patient caused by normally non-pathogenic organisms
• CD4: Helper T-cell, the primary target for HIV infection
• VL: Viral load; the amount of HIV viral RNA in the blood, typically reported in copies per mL; "undetectable" is <20 copies/mL.

Summary of the Global HIV Epidemic (2022)

• Total: 39.0 million people living with HIV (range: 33.1-45.7 million)
• Adults (15+): 37.5 million (range: 31.8-43.6 million)
• Women (15+): 20 million (range: 16.9-23.4 million)
• Men (15+): 17.4 million (range: 14.7-20.4 million)
• Children (<15): 1.5 million (range: 1.2-2.1 million)
• People acquiring HIV: 1.3 million (range: 1.0-1.7 million)
• HIV-related deaths: 630,000 (range: 480,000-880,000)

National Rate per 100,000 Population (Canada 2023)

• Total Rate: 6.1
• Increase of 35.2% in 2023 compared to 2022
• Most common exposure in adults is male-to-male sexual contact

Canada's Progress towards Meeting the 95-95-95 Targets (2022)

• 89% of people living with HIV (PLHIV) were diagnosed
• 85% of people diagnosed with HIV were on treatment
• 95% of those on treatment had a suppressed viral load
• 1 in 10 PLHIV did not know their status

HIV Transmission

• Infectious Body Fluids: Blood, semen, vaginal fluids, and "internal" body fluids (CSF, synovial, etc.) as well as fluids containing visible blood (tears, sweat, urine)

HIV Testing

• HIV testing should be a part of routine medical care
• Informed consent is not always necessary
• HIV is a reportable disease

Indications for HIV Testing

• Request for testing
• Sexually active and never tested
• Unprotected sex
• Unclear/positive partner HIV status
• Shared drug use equipment exposure
• Sexual assault
• Signs or symptoms of acute HIV infection
• Illnesses signaling immunosuppression (e.g., tuberculosis)
• Pregnancy or planning pregnancy

Risk Assessment for HIV Testing

• MSM (men who have sex with men) with multiple or anonymous partners
• Any individual using illicit drugs during sex

Clinical Presentation

• Varies depending on disease stage at diagnosis; may be asymptomatic or present with opportunistic infections
• Primary HIV infection associated with acute seroconversion syndrome
• Common symptoms: fever, lymphadenopathy, pharyngitis, rash, mucocutaneous ulcers, myalgia, arthralgia, diarrhea, headache, nausea, and vomiting

The Natural History of HIV Without ART

• CD4 count: Varies; typically starts high and decreases
• Viral load: High initially followed a period of decreased viral load via the use of ARV and high viral load

Goals of HIV Treatment

• Clinical goals: Slow disease progression; prevent OIs; prolong duration, and quality of life; minimize adverse effects; prevent resistance strains of HIV; prevent transmission
• Virological goals: Maximal and durable viral suppression (VL <20 copies/mL within 8–24 weeks)
• Immunological goals: Restore and/or preserve immunologic function (high CD4 count)

Non-Pharmacologic Therapy

• Counselling to address safer sex practices and drug use
• Importance of good nutrition and preventative health
• Vaccination with precautions for those with prior immunosuppressive conditions

Baseline Assessment at Diagnosis

• Medical history and physical exam
• Comorbidities
• Opportunistic infections
• HIV viral load
• CD4 count
• Screening for co-infections (e.g., STIs, hepatitis) and OIs
• HIV viral genotype testing
• HLA-B*5701 testing

Initiating ART

• ART is indicated for all patients with HIV infection
• If patient has OI treatment of the OI should be the priority, but treatment of HIV should start as soon as possible, potentially concurrently
• Caution with drug interactions with concurrent use of any medicine

Patient Follow-up

• Check-in at one month for adherence to plan and treatment tolerability
• Review concurrent medications carefully to rule out/manage drug interactions.
• Monitor VL regularly to assess initial response

Laboratory Monitoring

• Viral load (VL): Undetectable (<20 copies/mL)
• CD4 count: As high as possible (>200 cells/mm³)
• Lytes, SCr, glucose, AST, ALT, Tbili, Lipid profile: Normal levels
• Serum PO4: Normal (if applicable based on additional conditions)

Opportunistic Infections

• Patients do not die of HIV; they die of opportunistic infections, complications, malignancies, and ARV toxicities from older antiretroviral therapies
• Effective ARV therapy produces viable and durable immune reconstitution–most effective way to prevent OIs is through suppressive ARV therapy to maintain immune function

Prediction of OI risk

• Risk increases as CD4 count decreases
• Initiation of OIs prophylaxis is commonly indicated for patients with CD4<200
• Some non-opportunistic pathogens may still cause illness

"Common" OIs in HIV infection

• Several common pathogens including yeast (e.g., thrush), bacteria (e.g., oral hairy leukoplakia), and fungus (e.g., P. jirovecii pneumonia) cause OI following a confirmed HIV diagnosis
• TB is also considered an example of pathogen

Prediction of OI Risk

• Risks of OIs increase with declining CD4 counts
• Patients with CD4 counts < 200 typically warrant OI prophylaxis

CD4 < 200/ CD4 < 100/ CD4 < 50 Opportunistic Infections

• Common OIs with accompanying preventative treatments are presented
• Various OIs are detailed based on CD4 count classifications

Primary Prevention of OI

• Prevention is indicated for patients with certain CD4 counts and associated diagnoses or positive serologies

Case: FR

• 34-year-old man with HIV presenting to ED with symptoms (cough, dyspnea, and fever) that suggest opportunistic P. Jirovecii pneumonia (PJP)
• HIV is not fully controlled (VL 25000, CD4 120)
• Lab findings: indicate possible Pneumocystis jirovecii pneumonia (PJP)

PJP Pneumonia

• Caused by Pneumocystis jirovecii a unicellular fungus
• Primarily invades the lungs and less likely to invade extrapulmonary areas
• Previously known as PCP
• Primarily seen in immunocompromised patients
• Mortality is up to 33%

PJP Presentation

• Symptoms are usually slow and insidious, including fever and cough
• Chest X-ray and HRCT commonly indicate bilateral interstitial or alveolar infiltrates
• Sputum induction and bronchoalveolar lavage for testing frequently supports diagnosis
• PJP testing is highly sensitive for HIV in immunocompromised patients

PJP Treatment

• First-line treatment includes TMP-SMX (cotrimoxazole) for 21 days.
• Corticosteroids are often indicated to improve clinical outcomes if paO2 is less than 70, but only if administered within the first 72 hours
• Important to address drug interactions with any concurrent therapy
• Continuous use of secondary prevention measures are indicated until the CD4 count is above 200

Monitoring

• Clinical improvement
• Treatment toxicity (e.g., rash, fever, leukopenia, thrombocytopenia, hepatitis, hyperkalemia)
• Long-term CD4 recovery must also be monitored

HIV Prevention

• Use of ARVs for Prevention:
• Perinatal transmission
• Pre-Exposure Prophylaxis (PrEP)
• Post-Exposure Prophylaxis (PEP)

Perinatal Transmission

• Risk of transmission is approximately 25% without prophylaxis, reduced to <1% with appropriate ARV interventions
• Timing of perinatal transmission (in utero, intrapartum, breastfeeding). Effective ARV therapy (antepartum, intrapartum, and postpartum) and elective caesarian delivery as appropriate. Formula feeding
• If the pregnant person is not already on ARVs, they should initiate therapy ASAP, regardless of VL or CD4 count, and continue taking it

Prevention of Perinatal Transmission

• Opt-out HIV testing policy
• HIV testing during pregnancy (repeated in the second trimester)
• VL testing at 36 weeks if greater than 1000, consider C-section
• IV Zidovudine during labor
• Avoid artificial premature rupture of membranes
• Presumptive triple therapy (for babies) when mom's VL >50

Pre-Exposure Prophylaxis (PrEP)

• HIV-negative individuals use ART to reduce risk of infection
• Taken regularly, it significantly reduces the likelihood of becoming infected by greater than 90%
• Adherence is critical for PrEP effectiveness, and testing for other STIs is crucial

Who is a Candidate for PrEP?

• Men who have sex with multiple partners
• Heterosexual individuals with high-risk partners (including multiple partners and/or STI history)
• People who inject drugs
• HIV serodiscordant couples
• Note - there are exceptions for considerations regarding sex with an HIV+ partner if the HIV+ partner is on effective ARVs and maintaining an undetectable VL

What PrEP Options Exist?

• Oral TDF/emtricitabine (Truvada, generics); Oral TAF/emtricitabine (Descovy); Cabotegravir IM

PrEP is More Than Just a Drug

• Comprehensive monitoring is critical to adherence to PrEP and to exclude contracting other conditions (STIs, or HIV)
• Prescriptions typically are extended if HIV-negative status and absence of other STIs and further concerns are confirmed (every 3 months) and monitoring

Post-Exposure Prophylaxis (PEP)

• Occupational exposure (PEP)
• Non-occupational exposure (nPEP)
• Must start as soon as possible following exposure, ideally < 72 hours
• PEP is generally a combination treatment with 3 drugs and continued for 28 days
• PrEP may be a consideration for someone with frequently repeated nPEP exposures if it is deemed appropriate

When PEP is Considered

• Depends on: HIV status of source patient (if known), type and nature of exposure, type of body fluid, timing of exposure
• Significant Exposures Warrant PEP: HIV status of source unknown but from a population with high HIV prevalence, or from confirmed HIV (high or low viremia) and presence of an STI, or when patient status is unknown, from general population