🔴 HIV ANTIRETROVIRAL PHARMACOLOGY

🧠 BIG PICTURE (EXAM CORE)

• ART = combination therapy (usually 3 drugs)
• Aim:
• ↓ viral load → undetectable
• ↑ CD4 count
• Prevent resistance
• Standard regimen:

2 NRTIs + 1 INSTI (first-line worldwide)

1️⃣ NUCLEOSIDE / NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)

📌 Backbone of ART

🔬 Mechanism (CLASS)

• Analogues of natural nucleosides
• Phosphorylated intracellularly
• Incorporated into viral DNA → chain termination
• Inhibit reverse transcriptase

⚠️ Class toxicity:

Mitochondrial toxicity → lactic acidosis, hepatic steatosis

🔹 ZIDOVUDINE (AZT)

Mechanism

• Thymidine analogue
• Chain termination

PK

• Oral, IV
• Hepatic glucuronidation
• Crosses placenta ⭐

Adverse effects

• Bone marrow suppression (anemia, neutropenia) ⭐
• Myopathy
• Lactic acidosis

Drug interactions

• Additive marrow toxicity with ganciclovir

Resistance

• RT mutations (TAMs)

Pregnancy / Neonate ⭐⭐⭐

• KEY DRUG for vertical transmission prevention
• Used:
• Mother (antenatal/intrapartum)
• Neonate prophylaxis

📌 EXAM LOCK:

AZT → anemia + prevents mother-to-child transmission

🔹 LAMIVUDINE (3TC)

Mechanism

• Cytidine analogue

PK

• Renal excretion

Adverse effects

• Very well tolerated
• Rare pancreatitis

Extra

• Also active against HBV

📌 Exam: HIV + HBV → Lamivudine included

🔹 EMTRICITABINE (FTC)

• Similar to lamivudine
• Hyperpigmentation (palms/soles)
• Used in PrEP

🔹 TENOFOVIR (TDF / TAF)

Mechanism

• Nucleotide (no phosphorylation step needed)

PK

• Renal excretion

Adverse effects ⭐

• Nephrotoxicity
• ↓ Bone mineral density

📌 TAF = less renal & bone toxicity

📌 HIV + HBV + pregnancy → Tenofovir preferred

🔹 ABACAVIR

Key point ⭐⭐⭐

• HLA-B*5701 screening mandatory
• Risk: fatal hypersensitivity reaction

❌ Avoid in cardiovascular disease

🔹 DIDANOSINE, STAVUDINE (OLDER)

❌ Largely abandoned

• Pancreatitis
• Peripheral neuropathy
• Severe mitochondrial toxicity

2️⃣ NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs)

📌 Bind RT at a different site (non-competitive)

🔹 EFAVIRENZ

Mechanism

• Allosteric RT inhibition

Adverse effects ⭐⭐⭐

• Neuropsychiatric: vivid dreams, psychosis
• Rash
• Hepatotoxicity

Pregnancy ⚠️

• Avoid in 1st trimester (neural tube defects)

📌 Exam: Efavirenz = dreams

🔹 NEVIRAPINE

Adverse effects

• Severe hepatotoxicity
• Stevens–Johnson syndrome

📌 Used historically in PMTCT

🔹 DORAVIRINE / RILPIVIRINE

• Newer
• Better tolerated
• Less CNS toxicity

3️⃣ PROTEASE INHIBITORS (PIs)

📌 Block gag-pol cleavage → immature non-infectious virions

🔹 LOPINAVIR / RITONAVIR

Ritonavir role ⭐

• Potent CYP3A4 inhibitor
• Used as booster

Adverse effects (CLASS) ⭐⭐⭐

• Metabolic syndrome
• Lipodystrophy
• Hyperglycemia
• Dyslipidemia
• GI upset

Drug interactions ⚠️

• Massive CYP interactions

📌 Exam: Protease inhibitors = diabetes + fat redistribution

🔹 ATAZANAVIR

• Causes indirect hyperbilirubinemia
• Less dyslipidemia

🔹 DARUNAVIR

• High resistance barrier
• Used in resistant HIV

4️⃣ INTEGRASE STRAND TRANSFER INHIBITORS (INSTIs)

📌 FIRST-LINE TODAY

🔹 DOLUTEGRAVIR ⭐⭐⭐

Mechanism

• Blocks viral DNA integration

Advantages

• Rapid viral suppression
• High resistance barrier

Adverse effects

• Weight gain
• Insomnia

Pregnancy

• Safe after 1st trimester
• Current guidelines: preferred

📌 Exam: Best first-line drug today

🔹 RALTEGRAVIR

• Good safety
• Used in pregnancy

🔹 BICTEGRAVIR

• Fixed-dose combo
• Excellent tolerance

5️⃣ ENTRY & FUSION INHIBITORS

🔹 ENFUVIRTIDE

• Blocks gp41-mediated fusion
• Subcutaneous injection
• Injection-site reactions

🔹 MARAVIROC

• CCR5 antagonist
• Requires tropism testing

📌 Exam: Only works in CCR5-tropic virus

6️⃣ POST-EXPOSURE PROPHYLAXIS (PEP)

📌 Start within 72 hours

Standard PEP (28 days)

• Tenofovir + Emtricitabine

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• Dolutegravir / Raltegravir

7️⃣ PRE-EXPOSURE PROPHYLAXIS (PrEP)

📌 For high-risk individuals

• Tenofovir + Emtricitabine

8️⃣ HIV MANAGEMENT IN PREGNANCY ⭐⭐⭐

Mother

• Continue ART
• Preferred:
• Tenofovir + Lamivudine + Dolutegravir

Intrapartum

• IV Zidovudine if viral load high

Delivery

• Viral load >1000 → C-section

9️⃣ NEONATAL PROPHYLAXIS ⭐⭐⭐

• Zidovudine for 4–6 weeks
• High-risk neonate:
• AZT + Lamivudine + Nevirapine

🔴 ANTIRETROVIRAL DRUGS — COMPLETE EXAM MASTER TABLE

1️⃣ NUCLEOSIDE / NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)

📌 Backbone of ART

⚠️ Class toxicity (ALL NRTIs): Mitochondrial toxicity → lactic acidosis, hepatic steatosis

2️⃣ NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs)

📌 Non-competitive RT inhibitors

3️⃣ PROTEASE INHIBITORS (PIs)

📌 Block gag-pol cleavage → immature virions

⚠️ Class issue: Massive CYP-mediated drug interactions

4️⃣ INTEGRASE STRAND TRANSFER INHIBITORS (INSTIs)

📌 FIRST-LINE TODAY, They bind to the active site of HIV integrase

5️⃣ ENTRY & FUSION INHIBITORS

6️⃣ POST-EXPOSURE PROPHYLAXIS (PEP)

7️⃣ PRE-EXPOSURE PROPHYLAXIS (PrEP)

8️⃣ HIV MANAGEMENT IN PREGNANCY

9️⃣ NEONATAL PROPHYLAXIS

🧠 CONTRACEPTIVE COUNSELLING IN HIV — WITH DRUG INTERACTIONS (EXAM REFLEX BLOCK)

🔑 CORE COUNSELLING PRINCIPLES (ALWAYS SAY THESE)

1. Dual protection → contraception + condoms (STI & partner protection)
2. ART ≠ contraception
3. Check drug–drug interactions before choosing hormonal methods
4. No method is contraindicated just because of HIV status

1️⃣ SAFEST OPTIONS (NO DRUG INTERACTIONS)

✅ BARRIER METHODS

• Male / female condoms
• No interaction with ART
• Essential for dual protection

📌 Always recommend — even if another method used

✅ IUCDs (COPPER or LNG-IUS)

• Highly effective
• No interaction with ART
• Safe in HIV if:
• No active pelvic infection
• On stable ART

📌 Exam pearl: IUCDs are safe in HIV-positive women on ART

2️⃣ HORMONAL CONTRACEPTION — INTERACTION ZONE ⚠️

🔬 WHY INTERACTIONS HAPPEN

• Many ART drugs affect CYP450 enzymes
• ↓ Hormone levels → contraceptive failure

3️⃣ ART DRUGS THAT CAUSE PROBLEMS (MUST MEMORISE)

🚨 PROTEASE INHIBITORS (PIs)

(e.g. ritonavir, lopinavir)

• Strong CYP3A4 inhibitors/inducers
• ↓ estrogen & progestin levels
• ↑ failure of:
• Combined OCPs
• Progestin-only pills
• Implants (reduced efficacy)-jadelle fail

📌 Exam reflex:

Protease inhibitors reduce hormonal contraceptive effectiveness

🚨 NNRTIs

• Efavirenz (MOST IMPORTANT)
• Potent enzyme inducer
• ↓ implant & OCP efficacy
• Nevirapine → similar but less severe

📌 Efavirenz + implant = failure risk

✅ INSTIs (BEST WITH CONTRACEPTION)

• Dolutegravir
• Raltegravir
• Bictegravir

➡️ Minimal / no interaction with hormonal contraception

📌 Exam line:

INSTIs are contraception-friendly

4️⃣ METHOD-BY-METHOD QUICK GUIDE (EXAM GOLD)

5️⃣ DMPA (DEPOT MEDROXYPROGESTERONE) — EXAM FAVOURITE ⭐

• Unaffected by ART
• Effective with:
• PIs
• NNRTIs
• Suitable in:
• HIV-positive women
• Breastfeeding
• Those on enzyme-inducing ART

📌 If hormones needed → DMPA is safest

6️⃣ EMERGENCY CONTRACEPTION

• Levonorgestrel EC:
• ↓ efficacy with EFV / PIs
• Consider double dose
• Copper IUCD:
• Best emergency method
• No interaction

🔐 EXAM ONE-LINERS (DROP THESE)

• Condoms + ART = mandatory counselling
• PIs & Efavirenz reduce hormonal contraception efficacy
• DMPA and IUCDs are safest in HIV
• INSTIs have minimal contraceptive interactions
• Copper IUCD is best emergency contraception

🧠 FINAL EXAM-SAFE LINE 🔒

In HIV-positive women, dual protection is essential, IUCDs and DMPA are preferred due to lack of ART interactions, while protease inhibitors and efavirenz reduce the efficacy of most hormonal contraceptives.

🇱🇰 SRI LANKA NATIONAL GUIDELINE 2024

MANAGEMENT OF HIV-POSITIVE MOTHERS

(Antenatal → Intrapartum → Postpartum → Infant)

Source: National STD/AIDS Control Programme (NSACP), Ministry of Health Sri Lanka – EMTCT Guidelines 2024

PART 1 — ANTENATAL PERIOD

1️⃣ UNIVERSAL HIV SCREENING IN PREGNANCY

• All pregnant women should undergo opt-out HIV testing at the first antenatal clinic (ANC) visit, preferably before 12 weeks of gestation.
• Repeat HIV testing is recommended if:
• Ongoing high-risk behaviour
• HIV-positive partner
• Late booking
• Dual rapid tests for Human Immunodeficiency Virus (HIV) and syphilis are routinely used.

If HIV screening test is positive at ANC:

• The woman must be immediately referred to the STD clinic.
• HIV management must not be done solely at ANC level.
• Pre-test and post-test counselling is mandatory.

2️⃣ CONFIRMATION OF HIV IN STD CLINIC

At the STD clinic:

• HIV infection is confirmed using the national HIV testing algorithm.
• Baseline investigations:
• HIV viral load
• Cluster of Differentiation 4 count (CD4 count) – baseline only
• Full blood count
• Liver function tests
• Renal function tests
• Hepatitis B virus screening
• Hepatitis C virus screening
• Screening for other sexually transmitted infections
• Tuberculosis symptom screening

⚠️ Antiretroviral therapy must NOT be delayed while waiting for results.

3️⃣ ANTIRETROVIRAL THERAPY (ART) — START IMMEDIATELY

(OPTION B+ — LIFELONG ART)

Sri Lanka follows Option B+:

• All HIV-positive pregnant women receive lifelong antiretroviral therapy, regardless of CD4 count or clinical stage.

✅ PREFERRED FIRST-LINE REGIMEN IN PREGNANCY

• Tenofovir Disoproxil Fumarate (TDF)
• Emtricitabine (FTC) or Lamivudine (3TC)
• Dolutegravir (DTG)

👉 Written as: TDF + FTC/3TC + DTG

Reasons for preference:

• Rapid viral suppression
• High resistance barrier
• Safe in pregnancy and breastfeeding
• Once-daily dosing improves adherence

✅ ACCEPTABLE ALTERNATIVE REGIMENS (WHEN NEEDED)

Used if intolerance, contraindication, or drug unavailability:

• Tenofovir Alafenamide (TAF) + Emtricitabine (FTC) + Dolutegravir (DTG)
• Abacavir (ABC) + Lamivudine (3TC) + Dolutegravir (DTG)
• Zidovudine (AZT) + Lamivudine (3TC) + Dolutegravir (DTG)

Protease-inhibitor–based alternatives:

• Darunavir boosted with Ritonavir (DRV/r)
• Atazanavir boosted with Ritonavir (ATV/r)

Non-nucleoside reverse transcriptase inhibitor option:

• Efavirenz (EFV) (if already virologically suppressed)

⚠️ Two-drug antiretroviral regimens are NOT recommended in pregnancy.

4️⃣ WOMEN WHO CONCEIVE WHILE ALREADY ON ART

• Continue the existing regimen if:
• Viral load is suppressed
• No drug toxicity
• Do NOT switch drugs solely because the regimen is not “preferred”.
• Viral load monitoring should be more frequent.

5️⃣ ANTENATAL FOLLOW-UP & MONITORING

Viral load testing schedule:

• At diagnosis / ART initiation
• 2–4 weeks after starting ART
• Every 3 months
• Mandatory at approximately 36 weeks (critical for delivery planning)

Antenatal counselling must cover:

• ART adherence
• Partner testing
• Condom use
• Delivery planning
• Infant feeding options
• Postpartum contraception

PART 2 — INTRAPARTUM MANAGEMENT

6️⃣ DELIVERY PLANNING BASED ON VIRAL LOAD (AT ~36 WEEKS)

🔹 Viral load <50 copies/mL

• Planned vaginal delivery is acceptable
• Obstetric indications apply as usual

🔹 Viral load ≥50 copies/mL or unknown

• Elective caesarean section is preferred
• Strongly indicated if:
• Viral load >1000 copies/mL
• Poor adherence
• Late diagnosis

7️⃣ LABOUR MANAGEMENT PRINCIPLES (ALL WOMEN)

• Continue oral antiretroviral therapy
• Avoid:
• Fetal scalp electrodes
• Fetal blood sampling
• Artificial rupture of membranes
• Prolonged labour
• Instrumental delivery unless unavoidable
• Minimise genital tract trauma,Avoid routine episiotomy

8️⃣ PRE-LABOUR RUPTURE OF MEMBRANES (SROM-TERM)

9️⃣ INTRAPARTUM INTRAVENOUS ZIDOVUDINE — INDICATIONS

Intravenous Zidovudine (AZT) infusion is indicated if:

• Viral load >1000 copies/mL
• Woman presents in labour without prior ART
• Rupture of membranes with unknown viral load
• May be considered if viral load >50 copies/mL

🔟 WOMAN PRESENTING IN LABOUR — NOT ON ART

Emergency PMTCT protocol:

• Nevirapine 200 mg orally — stat dose
• Start:
• Zidovudine (AZT) + Lamivudine (3TC)
• PLUS Dolutegravir (DTG) or Raltegravir (RAL)
• Administer intravenous Zidovudine (AZT)
• Expedite delivery

⚠️ If delivery occurs within 2 hours of maternal Nevirapine, give Nevirapine to the newborn immediately.

PART 3 — POSTPARTUM CARE (MOTHER)

1️⃣ IMMEDIATE POST-DELIVERY CARE

• Early cord clamping
• Avoid suctioning infant mouth/pharynx
• Clean infant before injections
• Reduce postpartum haemorrhage risk
• Prompt repair of genital tract trauma

2️⃣ MATERNAL ART POSTPARTUM

• Continue lifelong antiretroviral therapy
• Regular follow-up at STD clinic
• Ongoing viral load monitoring

3️⃣ INFANT FEEDING — SRI LANKA POLICY

✅ SAFEST OPTION

• Exclusive formula feeding
• Eliminates postnatal HIV transmission

🔹 Breastfeeding — ONLY if ALL criteria met:

• Sustained maternal viral load suppression
• Excellent adherence
• Close multidisciplinary follow-up
• Monthly viral load testing (mother and infant)

⚠️ If acute maternal HIV infection occurs during breastfeeding → STOP breastfeeding immediately.

Lactation suppression:

• Cabergoline is offered to suppress lactation if not breastfeeding

PART 4 — INFANT MANAGEMENT

1️⃣ INFANT RISK STRATIFICATION

LOW-RISK INFANT

• Mother on ART early
• Sustained viral load <50 copies/mL
• Good adherence

HIGH-RISK INFANT

• No antenatal care
• No or late ART
• Viral load >50 copies/mL near delivery
• Acute maternal infection
• Unknown maternal status

2️⃣ INFANT ANTIRETROVIRAL PROPHYLAXIS

(START WITHIN 6 HOURS OF BIRTH)

LOW RISK (NOT BREASTFED)

• Nevirapine (NVP) or Zidovudine (AZT)
• Duration: 4–6 weeks

HIGH RISK (NOT BREASTFED)

• Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP)

or

• Zidovudine (AZT) + Lamivudine (3TC) + Raltegravir (RAL)
• Duration: 4–6 weeks

BREASTFED INFANTS

• Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP)
• Duration: 12 weeks OR until maternal viral load <50 copies/mL

3️⃣ COTRIMOXAZOLE PROPHYLAXIS

• Cotrimoxazole prophylaxis begins at 4 weeks of age if:
• HIV infection is confirmed
• Or HIV status has not yet been excluded

4️⃣ EARLY INFANT DIAGNOSIS (EID)

⚠️ HIV antibody tests are NOT diagnostic in infants <18 months

NON-BREASTFED INFANTS

• HIV DNA/RNA PCR at:
• Birth (within 48 hours)
• 8 weeks
• 4–6 months
• HIV antibody tests:
• 9 months
• 18 months

BREASTFED INFANTS

• PCR at:
• Birth
• 2 weeks
• Every 3 months during breastfeeding
• 4–6 weeks, 3 months, and 6 months after stopping breastfeeding
• Antibody testing ≥8 weeks after breastfeeding cessation

5️⃣ IF INFANT PCR IS POSITIVE

• Start full antiretroviral therapy immediately
• Do NOT wait for confirmatory result
• Send second sample for confirmation in parallel

✅ FINAL CLINICAL LOCK

• ART immediately, lifelong
• Viral load at 36 weeks determines delivery
• Intravenous Zidovudine if suggesting high risk
• Formula feeding safest
• Infant prophylaxis within 6 hours
• PCR-based diagnosis only