HIV Therapies Lecture

What is the standard first-line ART regimen class combination for ART‑naïve patients?

Two NRTIs(Nukes) + one INSTI (preferred backbone for most patients).

What are examples of recommended INSTI-based first-line regimens? Integrase strand transfer inhibitor aka integrase inhibitor

BIC/TAF/FTC (Biktarvy); DTG + TAF/FTC or TDF/FTC; DTG/3TC (if HIV RNA <500k, no HBV coinfection).

Why are INSTI-based regimens preferred?

High potency, rapid viral load decline, excellent tolerability, minimal drug interactions, high resistance barrier.

When is ABC(Abacavir)/3TC(Lamivudine) avoided?

HLA‑B*57:01 positive (risk of fatal hypersensitivity), or in HBV coinfection (ABC does not treat HBV).

What are the expected benefits of antiretrovirals beyond CD4 increase?

Prevents HIV transmission (U=U), reduces OI risk, decreases inflammation, lowers cardiovascular and renal disease risk, improves survival.

What does U = U mean?

Undetectable viral load = untransmittable; patients with sustained suppression do not sexually transmit HIV.

When should antiretrovirals be started?

For ALL patients with HIV regardless of CD4 count (A1 recommendation).

What situations increase urgency to start ART?

CD4 <200, pregnancy, AIDS-defining illness, HIV-associated nephropathy, HBV/HCV coinfection, discordant couples(one is positive and the other is negative).

What is the role of NRTIs? (Nukes)

Nucleoside analogs that inhibit reverse transcriptase by chain termination.

What are common NRTIs?

TAF+TDF(Tenofovir), FTC(Emtricitabine), 3TC(Lamivudine), ABC(Abacavir), AZT(Zidovudine).

What toxicity is associated with TDF?

Renal dysfunction and decreased bone mineral density.

What advantages does TAF have over TDF?

Lower renal and bone toxicity; higher intracellular drug levels. (TAFfy is better than D)

What is abacavir hypersensitivity associated with?

HLA‑B*57:01 allele; must test before prescribing.

What is the role of NNRTIs? (Non-Nukes)

Bind allosterically to reverse transcriptase; non‑competitive inhibition.

What are limitations of rilpivirine?

Not effective if HIV RNA >100,000 or CD4 <200; requires food; interacts with acid suppressants.

What is the role of protease inhibitors (PIs)?

Block viral protease, preventing maturation of virions; high resistance barrier.

Why are PIs often “boosted”?

Ritonavir or cobicistat inhibit CYP450 to increase PI levels and reduce it from being metabolized.

What is the role of integrase inhibitors (INSTIs)?

Block integration of viral DNA into host genome; cornerstone of modern antiretrovirals.

What is Cabenuva?

Long‑acting injectable cabotegravir + rilpivirine; used only if virologically suppressed with no resistance.

What is required before starting Cabenuva?

No history of treatment failure, no INSTI/NNRTI resistance, and stable viral suppression.

What ART regimens treat both HIV and HBV?

TAF or TDF(Tenofovir) + FTC or 3TC (must include two HBV‑active agents).

What is PrEP?

Pre‑exposure prophylaxis to prevent HIV infection.

What medications are used for PrEP?

Emtricitabine + TDF (Truvada) or Emtricitabine + TAF (Descovy); or injectable cabotegravir. (Prep yourself Emmit 10)