Antiretroviral Drugs

Antiretroviral drugs suppress HIV replication, restore CD4 counts, prevent transmission and cure no one, so treatment is lifelong. Regimens combine at least two, usually three, fully active drugs from different classes. A suppressed viral load (under 200 copies/mL, ideally under 50) prevents sexual transmission and mother-to-child transmission.

Classes and targets.

• Nucleoside and nucleotide reverse transcriptase inhibitors: terminate viral DNA chains.
• Nonnucleoside reverse transcriptase inhibitors: bind reverse transcriptase allosterically.
• Protease inhibitors: block maturation of viral proteins.
• Integrase strand transfer inhibitors: block integration of viral DNA.
• Entry inhibitors and capsid inhibitors: block attachment, co-receptor binding, fusion or capsid function.
• Pharmacokinetic boosters (ritonavir, cobicistat): raise levels of partner drugs.

• Preferred first-line combination for adults and adolescents: tenofovir disoproxil 300 mg, lamivudine 300 mg and dolutegravir 50 mg in one tablet once daily.
• Alternatives: efavirenz-based regimens, or tenofovir alafenamide, emtricitabine and bictegravir.
• Children: abacavir, lamivudine and dolutegravir by weight band; boosted lopinavir for very young infants.
• Second-line after failure of a dolutegravir regimen: a boosted protease inhibitor (darunavir or atazanavir with ritonavir) with a new nucleoside backbone chosen by resistance results where available.
• Long-acting injectable cabotegravir with rilpivirine, given every 2 months, is an option for suppressed patients where available.

When to start. All people with HIV, regardless of CD4 count, ideally within days of diagnosis once ready.

• Tuberculosis: start within 2 weeks if CD4 is under 50 cells/mm3, otherwise within 8 weeks. Tuberculous meningitis: delay, with specialist input.
• Cryptococcal meningitis: delay 4 to 6 weeks after antifungal start.
• Advanced HIV disease (CD4 under 200 cells/mm3 or clinical stage 3 or 4 illness): give prophylaxis against opportunistic infection and screen for tuberculosis and cryptococcal antigen.

Monitoring response. Viral load at 6 months, at 12 months, and then yearly. Suppression is under 1000 copies/mL by programme definition, with under 50 copies/mL the clinical aim. A viral load of 1000 copies/mL or more on two measures 3 months apart, with adherence support between them, defines failure and triggers a resistance-informed switch.

Interactions that change dosing.

• Rifampicin: dolutegravir 50 mg twice daily; protease inhibitors are avoided or replaced by rifabutin-based treatment.
• Polyvalent cations lower integrase inhibitor absorption: give dolutegravir 2 hours before or 6 hours after calcium, iron, magnesium or aluminium products, or with food.

Pregnancy and breastfeeding. Dolutegravir-based treatment is preferred before conception and in all trimesters. Continue treatment in breastfeeding.

Region. In East Africa, the fixed-dose tenofovir, lamivudine and dolutegravir tablet is widely used as first-line in public programmes. Hepatitis B and tuberculosis coinfection are frequent, and both change the choice and timing of drugs.

Baseline tests. HIV viral load and CD4, creatinine, hepatitis B surface antigen (this decides whether tenofovir must be continued), pregnancy test, tuberculosis screen, cryptococcal antigen if CD4 under 200 cells/mm3, glucose and lipids when indicated.

Class safety. Weight gain and metabolic change with integrase inhibitors; renal and bone effects with tenofovir disoproxil; hypersensitivity with abacavir; neuropsychiatric effects with efavirenz; lipid and glucose effects with protease inhibitors; immune reconstitution inflammatory syndrome after starting.

Common prescribing errors. Stopping tenofovir, lamivudine or emtricitabine in hepatitis B coinfection (risks severe flare); omitting the double dolutegravir dose with rifampicin; adding a single new drug to failing treatment; ignoring cation interactions.

Special groups.

• Kidney impairment: avoid tenofovir disoproxil when creatinine clearance is under 50 mL/min; use tenofovir alafenamide or abacavir.
• Liver disease: avoid nevirapine; adjust protease inhibitors.
• Children and adolescents: weight-banded dosing and adherence support.

Referral and escalation. Refer confirmed failure, suspected resistance, immune reconstitution syndrome, and pregnancy with detectable viral load.