HIV & AIDS STRATEGIES

LAONE WAME NTSHO 2023080525

KATLEGO JOY RAMOHIBIDU 2023080464
SAMANTHA MMAPADI 2023080543
MOJABOSWA TSHEPHO MOTSAMAI 2023080529
GORATA GEORGE 2023080519
SALIKI MONTHE 2023080542
KAGISO MAKHURA 2023080039
BOFELO MALAELA 2023080506
THOBO TSHEPHO KETLOGETSWE 2023080553
HND IN PHARMACY TECHNOLOGY
MS TUMOTUMO
 HIV & AIDS STRATEGIES
Anti-Retroviral Drugs

1. Overview of the Drugs

Antiretroviral drugs (ARVs) are crucial for managing HIV infection. They work by inhibiting
various stages of the viral life cycle, thereby reducing viral load, improving immune function,
and preventing the progression to AIDS. The Botswana 2023 guidelines emphasize the
importance of ART (antiretroviral therapy) as a lifelong treatment that significantly enhances the
quality of life and reduces the risk of HIV transmission.

2. Classification
ARVs are classified into six main categories based on their mechanism of action:
NRTIs (Nucleoside Reverse Transcriptase Inhibitors)
NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors)
PIs (Protease Inhibitors)
INSTIs (Integrase Strand Transfer Inhibitors)
Entry Inhibitors (Fusion Inhibitors and CCR5 Antagonists)
Pharmacokinetic Enhancers

3. A List of All Drugs Available Under Each Class and Their Dosages

1. NRTIs
Zidovudine (AZT)
Adults: 300 mg orally twice daily
Pediatrics: 4 mg/kg every 12 hours
Pregnant Women: 300 mg orally twice daily (with specific regimens during labor)

Lamivudine (3TC)
Adults: 150 mg orally twice daily or 300 mg once daily
Pediatrics: 4 mg/kg once daily

Pregnant Women: 150 mg orally twice daily

Abacavir (ABC)
Adults: 300 mg orally twice daily
Pediatrics: 8 mg/kg twice daily (max 300 mg)
Pregnant Women: 300 mg orally twice daily

Emtricitabine (FTC)
Adults: 200 mg orally once daily
Pediatrics: 6 mg/kg once daily (max 200 mg)
Pregnant Women: 200 mg orally once daily

Tenofovir disoproxil fumarate (TDF)

Adults: 300 mg orally once daily
Pediatrics: 8 mg/kg orally once daily
Pregnant Women: 300 mg orally once daily

2. NNRTIs
Efavirenz (EFV)
Adults: 600 mg orally once daily
Pediatrics: 15 mg/kg once daily (max 600 mg)
Pregnant Women: Not recommended in the first trimester

Nevirapine (NVP)
Adults: 200 mg orally once daily for 14 days, then 200 mg twice daily
Pediatrics: 4 mg/kg once daily for 14 days, then 7 mg/kg twice daily
Pregnant Women: 200 mg orally once daily for 14 days, then 200 mg twice daily

Etravirine (ETR)
Adults: 200 mg orally twice daily
Pediatrics: 5 mg/kg twice daily (max 200 mg)
Pregnant Women: 200 mg orally twice daily

Rilpivirine (RPV)
Adults: 25 mg orally once daily
Pediatrics: 15 mg/kg (max 25 mg) once daily
Pregnant Women: 25 mg orally once daily

3.PIs
Lopinavir/ritonavir (LPV/r)
Adults: 400/100 mg orally twice daily
Pediatrics: 10 mg/kg/2.5 mg/kg twice daily
Pregnant Women: 400/100 mg orally twice daily

Atazanavir (ATV)
Adults: 300 mg orally once daily
Pediatrics: 10 mg/kg once daily (max 300 mg)
Pregnant Women: 300 mg orally once daily

Darunavir (DRV)
Adults: 800 mg orally once daily (with 100 mg ritonavir)
Pediatrics: 8 mg/kg once daily (max 800 mg)
Pregnant Women: 800 mg orally once daily (with 100 mg ritonavir)

4. INSTIs
Raltegravir (RAL)
Adults: 400 mg orally twice daily
Pediatrics: 5 mg/kg twice daily (max 400 mg)

Pregnant Women: 400 mg orally twice daily

Dolutegravir (DTG)
Adults: 50 mg orally once daily
Pediatrics: 2 mg/kg once daily (max 50 mg)
Pregnant Women: 50 mg orally once daily

Bictegravir (BIC)
Adults: 50 mg orally once daily
Pediatrics: Not currently recommended
Pregnant Women: Not enough data for recommendation

5. Entry Inhibitors
Enfuvirtide (T-20)
Adults: 90 mg subcutaneously twice daily
Pediatrics: 2 mg/kg (max 90 mg) subcutaneously twice daily
Pregnant Women: Not enough data for recommendation

Maraviroc (MVC)
Adults: 300 mg orally twice daily
Pediatrics: 4 mg/kg (max 300 mg) orally twice daily
Pregnant Women: Not enough data for recommendation

3.6 Pharmacokinetic Enhancers

Ritonavir (RTV)
Adults: 100 mg orally once or twice daily as a booster
Pediatrics: 1-2 mg/kg twice daily
Pregnant Women: 100 mg orally twice daily (as a booster)
4. Mechanism of Action for Each Class (Relate it to the Pathophysiology)

1. NRTIs
Mechanism: NRTIs mimic natural nucleosides, getting incorporated into the viral DNA during
reverse transcription, leading to chain termination.
Pathophysiology: This action disrupts the conversion of viral RNA to DNA, preventing viral
replication.

2. NNRTIs
Mechanism: NNRTIs bind directly to reverse transcriptase, causing a conformational change that
inhibits the enzyme's activity.
Pathophysiology: By preventing reverse transcription, these drugs halt the formation of viral
DNA.

3. PIs
Mechanism: PIs inhibit the protease enzyme, essential for processing viral polyproteins into
functional proteins.
Pathophysiology: This prevents the maturation of viral particles, resulting in the release of
immature, non-infectious virions.

4. INSTIs
Mechanism: INSTIs block integrase, the enzyme that integrates viral DNA into the host genome.
Pathophysiology: By inhibiting integration, INSTIs prevent the establishment of a latent viral
reservoir in host cells.

5. Entry Inhibitors
Mechanism: Fusion inhibitors block the virus from fusing with the host cell membrane, while
CCR5 antagonists prevent HIV from binding to the CCR5 co-receptor.
Pathophysiology: These actions prevent viral entry into T-cells, stopping the viral life cycle early.

5. The Common Side Effects for Each Drug

1. NRTIs
Zidovudine: Bone marrow suppression, nausea, fatigue.
Lamivudine: Headache, fatigue, gastrointestinal upset.
Abacavir: Hypersensitivity reactions, nausea, fatigue.
Emtricitabine: Skin rash, gastrointestinal symptoms.
Tenofovir: Renal toxicity, bone density loss.

2. NNRTIs
Efavirenz: Neuropsychiatric symptoms (insomnia, vivid dreams), rash.
Nevirapine: Rash, liver toxicity.
Etravirine: Rash, gastrointestinal side effects.
Rilpivirine: Depression, headache, insomnia.

3. PIs
Lopinavir/ritonavir: Diarrhea, hyperlipidemia, pancreatitis.
Atazanavir: Hyperbilirubinemia, abdominal pain.
Darunavir: Rash, gastrointestinal symptoms, liver toxicity.

4. INSTIs
Raltegravir: Rash, nausea, insomnia.
Dolutegravir: Insomnia, headache, weight gain.
Bictegravir: Diarrhea, headache, weight gain.

5. Entry Inhibitors
Enfuvirtide: Injection site reactions, diarrhea.
Maraviroc: Cough, upper respiratory infections, liver toxicity.
6. Pharmacokinetic Enhancers
Ritonavir: Nausea, vomiting, diarrhea, and changes in lipid metabolism.

Cobicistat: Gastrointestinal symptoms, increased serum creatinine.

6. Contraindications to Using the Drug

1 NRTIs
Zidovudine: Hematologic abnormalities (e.g., anemia, neutropenia).
Lamivudine: Hypersensitivity to the drug.
Abacavir: History of hypersensitivity reaction to abacavir.
Emtricitabine: Hypersensitivity reactions.
Tenofovir: Renal impairment (CrCl < 50 mL/min).

2. NNRTIs
Efavirenz: Pregnancy (first trimester), severe liver disease.
Nevirapine: Severe hepatic impairment, initiating in women with CD4 counts > 250 cells/mm³
and men > 400 cells/mm³ due to risk of hepatotoxicity.
Etravirine: Hypersensitivity, co-administration with potent CYP inducers.
Rilpivirine: Use with certain proton pump inhibitors, uncontrolled HIV replication.

3. PIs
Lopinavir/ritonavir: History of hypersensitivity, severe liver impairment.
Atazanavir: Severe liver disease, co-administration with certain drugs that increase atazanavir
levels.
Darunavir: History of hypersensitivity to darunavir or sulfonamides, severe hepatic impairment.

4. INSTIs
Raltegravir: Severe hypersensitivity reactions.
Dolutegravir: Pregnancy (first trimester, unless benefits outweigh risks), hypersensitivity.
Bictegravir: Not recommended in patients with severe hepatic impairment.
5. Entry Inhibitors
Enfuvirtide: Hypersensitivity, concurrent use with agents that increase injection site reactions.
Maraviroc: Severe renal impairment, active hepatitis.

6 Pharmacokinetic Enhancers
Ritonavir: Use in patients with severe liver impairment, hypersensitivity.
Cobicistat: Severe hepatic impairment.

7. Possible Drug Interactions

1. NRTIs
NRTIs generally have fewer drug interactions but can interact with drugs that affect renal
function (e.g., NSAIDs for Tenofovir).

2. NNRTIs
Efavirenz: Induces CYP3A4; can reduce levels of other drugs (e.g., contraceptives).
Nevirapine: Induces CYP3A4 and may affect levels of other drugs metabolized by this enzyme.

3. PIs
Lopinavir/ritonavir: Strong CYP3A4 inhibitor; can increase levels of many drugs (e.g., statins,
benzodiazepines).
Atazanavir: Requires acid for absorption; interactions with proton pump inhibitors, antacids, and
H2 blockers.

4. INSTIs
Raltegravir: Few significant interactions but can be affected by multivalent cations (calcium,
magnesium).
Dolutegravir: Interactions with drugs that induce or inhibit UGT1A1, including rifampin.
5. Entry Inhibitors
Maraviroc: Interactions with CYP3A4 inhibitors and inducers.

6. Pharmacokinetic Enhancers
Ritonavir: Affects the metabolism of many drugs due to CYP3A4 inhibition.
Cobicistat: Similar interactions as ritonavir, specifically with drugs metabolized by CYP3A4.
 REFERENCES

1. Botswana Ministry of Health and Wellness. (2016). Botswana integrated HIV clinical care
guidelines. Retrieved from https://www.health.gov.bw/

2. Botswana Ministry of Health and Wellness. (2023). Botswana integrated HIV clinical care
guidelines. Retrieved from https://www.health.gov.bw/

3. World Health Organization. (2016). Guidelines for the use of antiretroviral therapy for treating
and preventing HIV infection. Retrieved from
https://www.who.int/publications/i/item/9789241549708