HIV/AIDS Pharmacology (ART): How to Master Antiretroviral Combinations, This Is a Core Competency for Clinical and Retail Pharmacists

HIV/AIDS Pharmacology (ART): How to Master Antiretroviral Combinations, This Is a Core Competency for Clinical and Retail Pharmacists

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Antiretroviral therapy (ART) is now simple to take but still complex to choose, adjust, and monitor. Pharmacists who master combinations, interactions, and patient-specific factors prevent failure, resistance, and harm. This guide gives you a fast, practical way to evaluate any ART regimen, explain the “why” behind the design, and act quickly when something doesn’t fit.

The core rule: two NRTIs plus a high-barrier third agent

Modern ART usually pairs two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) with one potent anchor drug. This works because NRTIs block viral replication at the backbone level, while the anchor adds potency and raises the resistance barrier. High-barrier agents tolerate occasional missed doses without losing control of the virus.

  • Backbone (pick one pair): TAF/FTC, TDF/FTC, or ABC/3TC.
  • Anchor (prefer high barrier): Dolutegravir (DTG), Bictegravir (BIC), or boosted Darunavir (DRV/r or DRV/c).

Why not other anchors? Raltegravir (RAL) and elvitegravir (EVG) have lower resistance barriers. Older NNRTIs (efavirenz, nevirapine) cause more CNS or hepatic toxicity and interact heavily. We still use NNRTIs like rilpivirine (RPV) or doravirine (DOR) in select cases for simplicity or tolerability, but with conditions.

Know your building blocks

  • NRTIs
    • TAF vs TDF: TAF is gentler on kidneys and bone but can raise lipids and weight. TDF is cheaper and good for lipids but risks renal tubulopathy and bone loss.
    • FTC and 3TC: Interchangeable for HIV; both active against HBV. Be careful: stopping them in HBV coinfection can trigger flares.
    • Abacavir (ABC): Requires HLA-B*57:01 negative status. Avoid in high cardiovascular risk due to possible MI association.
  • Integrase inhibitors (INSTIs)
    • BIC, DTG: Once daily, high barrier, few interactions. Can cause weight gain and mild neuropsychiatric symptoms.
    • RAL, EVG/c: Lower barrier; EVG needs cobicistat (many interactions).
    • Class interaction: All INSTIs chelate with polyvalent cations—separate from antacids, iron, and calcium.
  • Protease inhibitors (PIs)
    • Darunavir (boosted with ritonavir or cobicistat): Very high barrier; useful when resistance or adherence concerns exist.
    • Class effects: GI upset, dyslipidemia, insulin resistance; many CYP3A interactions (due to boosters).
  • NNRTIs
    • Rilpivirine (RPV): Simple, but requires low gastric pH and a meal. Do not use with high viral load or low CD4 at start (failure risk).
    • Doravirine (DOR): Better interaction profile; retains activity with some K103N mutations.
  • Boosters
    • Ritonavir, Cobicistat: Potent CYP3A inhibitors. They raise levels of the PI and many other drugs. Cobicistat also raises serum creatinine by blocking tubular secretion (no true GFR drop).

First-line regimens to recognize quickly

  • BIC/TAF/FTC (one tablet daily): First choice for many adults. High barrier, minimal interactions.
  • DTG + TAF/FTC (two tablets) or DTG/3TC (single tablet): DTG/3TC only if HBV is excluded, baseline viral load <500,000, and no resistance to 3TC.
  • DRV/c + TAF/FTC (single tablet): Use when resistance or adherence issues exist; more interactions and metabolic effects.
  • RPV/TAF/FTC (single tablet): Only if starting viral load <100,000 and CD4 >200; must take with a meal and avoid PPIs.

Why these? They balance potency, simplicity, and safety. High-barrier INSTIs handle occasional missed doses; once-daily dosing improves adherence. We avoid regimens that require strict acid or food conditions unless clearly indicated.

When special conditions change the plan

  • HBV/HIV coinfection: Include two HBV-active NRTIs (TDF or TAF + FTC/3TC). Do not stop these without coverage (risk of HBV flare). If TDF/TAF can’t be used, add entecavir with fully suppressive ART.
  • Pregnancy: Prefer DTG + TDF/FTC, RAL + TDF/FTC, or DRV/r (BID) + TDF/FTC. Avoid cobicistat-boosted regimens (low levels in pregnancy). RPV levels drop late in pregnancy—monitor viral load closely.
  • Tuberculosis therapy: Rifampin lowers INSTI and PI levels.
    • With DTG: increase to 50 mg BID while on rifampin.
    • Avoid EVG/c and all boosted PIs with rifampin.
    • RPV is contraindicated with rifamycins.
  • Renal disease: Prefer TAF over TDF when eGFR <60. Dose-adjust 3TC and FTC as kidney function declines. ABC does not need renal adjustment.
  • Cardiovascular risk: Avoid ABC if high risk. PIs raise lipids; consider switching to INSTI-based regimens.
  • Bone disease: Avoid TDF in osteoporosis; choose TAF or ABC (if eligible).

Drug–drug interactions you must not miss

  • Acid suppression
    • Rilpivirine or Atazanavir: PPIs contraindicated. H2 blockers require spacing; antacids separate by several hours.
    • Why: These drugs need gastric acidity for absorption; high pH reduces exposure and risks failure.
  • Polyvalent cations (antacids, iron, calcium, magnesium, phosphate binders)
    • All INSTIs: Separate. Example: take DTG/BIC 2 hours before or 6 hours after antacids; iron/calcium may be coadministered with food (check product specifics).
  • Boosters (ritonavir/cobicistat)
    • Statins: Avoid simvastatin and lovastatin. Use low-dose atorvastatin or prefer pravastatin/pitavastatin; titrate carefully.
    • Anticoagulants: Levels of DOACs can rise; consider alternatives or close monitoring. Warfarin may require dose changes.
    • Sedatives/antiepileptics: Carbamazepine, phenytoin, phenobarbital, and St. John’s wort lower ARV levels—avoid.
  • Metformin with DTG: DTG increases metformin exposure—cap metformin at usual max dose and monitor GI effects and glucose.
  • Dofetilide with DTG: Contraindicated (DTG raises dofetilide levels via OCT2 inhibition).
  • Methadone/buprenorphine: Efavirenz lowers methadone—watch for withdrawal; adjust as needed. Most INSTIs have minimal effect.
  • Hormonal contraception: Boosted PIs may reduce ethinyl estradiol; consider IUDs or injectables, or adjust formulation per label.

Side effects worth anticipating

  • Weight and metabolic changes: More with INSTIs (DTG/BIC) and TAF. Explain early and monitor BMI, lipids, and glucose so lifestyle or medication changes can follow.
  • Neuropsychiatric: Insomnia, vivid dreams, anxiety—especially with efavirenz; milder with DTG/BIC. Dose at night or switch if persistent.
  • Renal and bone: TDF can cause proximal tubulopathy and bone loss—check creatinine, urinalysis, and phosphate if symptoms.
  • Hyperbilirubinemia: Atazanavir inhibits UGT1A1 causing benign jaundice; reassure if labs fit and liver enzymes are normal.
  • Hypersensitivity: Abacavir can cause severe reaction—never start without HLA-B*57:01 testing; never rechallenge after a reaction.
  • GI and lipid effects: Common with boosted PIs; consider statin choice and diet counseling.

Monitoring that prevents failure

  • Before start/switch: HIV RNA, CD4, genotype (RT/PR; add integrase if concern), HBsAg/anti-HBc/anti-HBs, pregnancy test, CMP, renal function, fasting lipids/glucose, STI screen, TB testing.
  • After start: Viral load at 4 weeks, then every 4–8 weeks until suppressed, then every 3–6 months. Check adherence at every touchpoint.
  • Safety labs: Renal and liver function at baseline and 1–3 months, then periodically. Lipids and glucose at 3–6 months after starting or switching to TAF or PIs.

Retail and clinic pharmacist workflow: five fast moves

  • Verify the anchor-backbone logic: Is this two NRTIs plus a high-barrier third? If not, is there a documented reason (e.g., DTG/3TC criteria met)?
  • Screen for co-conditions: HBV status, pregnancy, TB therapy, eGFR, ASCVD risk. These often change the “best” regimen.
  • Run interaction triage: Look for acid suppression, cations, boosters with statins/anticoagulants, antiepileptics, dofetilide, metformin.
  • Counsel for success:
    • Timing: once daily at the same time; with food when required (RPV, ATV, DRV).
    • Missed doses: take when remembered unless near the next dose; do not double.
    • Antacids and vitamins: separate from INSTIs; give exact hour gaps.
    • HBV coinfection: never stop TDF/TAF + FTC/3TC abruptly.
  • Adherence support: Sync refills, 90-day supplies when allowed, enroll in reminders, and address cost barriers proactively.

Switching and simplification: when and how

  • Improve safety: Switch TDF to TAF in CKD or osteoporosis; move from PI to INSTI for lipids and fewer interactions.
  • Maintain coverage: Confirm historical resistance before dropping drugs. For past M184V, many keep 3TC/FTC for viral fitness cost despite resistance.
  • Use high barriers for adherence risk: DTG/BIC or boosted DRV tolerate occasional lapses better.
  • Simplify pills: Single-tablet regimens help, but never at the expense of HBV coverage or interaction pitfalls.

Common pitfalls and how to avoid them

  • Starting DTG/3TC without ruling out HBV: Risks HBV flare and under-treatment.
  • Giving RPV with a PPI or without a meal: Leads to subtherapeutic levels and virologic failure.
  • Overlooking cation separation with INSTIs: A simple multivitamin can drop drug exposure.
  • Using ABC without HLA-B*57:01: Avoidable hypersensitivity reactions.
  • Combining boosted PIs with simvastatin/lovastatin: Severe myopathy risk.
  • Stopping TDF/TAF + FTC/3TC in HBV coinfection: HBV flare and hepatic decompensation risk.

One-page mental model

  • Pick the backbone: TAF/FTC (kidney/bone friendly), TDF/FTC (lipid friendly), or ABC/3TC (if HLA-B*57:01 negative and low ASCVD risk).
  • Pick the anchor: DTG or BIC for most; boosted DRV if resistance/adherence concerns; RPV or DOR in selected low-risk cases.
  • Check modifiers: HBV, pregnancy, TB therapy, eGFR, ASCVD, osteoporosis, baseline VL/CD4.
  • Scan interactions: Acid suppression, cations, CYP3A issues, OCT2 (dofetilide, metformin).
  • Plan follow-up: Viral load at 4 weeks, labs at 1–3 months, adherence every visit.

Pharmacists make ART safe and sustainable by seeing the whole picture: the right combo for the virus, the right fit for the person, and the right plan for the rest of their medicines and conditions. With a firm grasp of these patterns and pitfalls, you can evaluate any regimen quickly and intervene with confidence.

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