What is the recommended first-line regimen for HIV treatment in India?

HIV Treatment in India: Recommended First-Line Regimen

In India, the recommended first-line regimen for HIV treatment should be an integrase strand transfer inhibitor (InSTI)-based combination, with dolutegravir plus tenofovir/lamivudine being the most practical choice given resource considerations and drug availability. 1, 2

Optimal First-Line Regimens

Primary Recommendation

• Dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine is the preferred regimen for most patients due to high efficacy, favorable side effect profile, and high barrier to resistance 3, 1
• Dolutegravir/abacavir/lamivudine is equally effective but requires mandatory HLA-B*5701 testing before initiation to prevent potentially life-threatening hypersensitivity reactions 3, 1, 2
• Bictegravir/TAF/emtricitabine represents another excellent option with similar efficacy, though it has less long-term safety data compared to dolutegravir 3, 1

Alternative Regimens When InSTI-Based Options Are Unavailable

If the above regimens are not accessible in India, the following alternatives are recommended:

• Efavirenz/TDF/emtricitabine remains a viable option with strong evidence (AIa rating), particularly in resource-limited settings 3
• Darunavir boosted with ritonavir plus TAF (or TDF)/emtricitabine is recommended when InSTI resistance is suspected 3, 1
• Raltegravir plus TAF (or TDF)/emtricitabine provides another InSTI-based alternative 3

Critical Pre-Treatment Considerations

Mandatory Testing Before Initiation

• HLA-B*5701 testing is absolutely required before prescribing any abacavir-containing regimen, as approximately 50% of positive individuals will experience potentially life-threatening hypersensitivity reactions 3, 1, 2
• HIV-1 RNA level, CD4 cell count, and HIV genotype for resistance testing should be drawn, but treatment may begin before results are available 3
• Hepatitis B and C screening is essential, as co-infection affects regimen selection 2, 4

Timing of Treatment Initiation

• ART should be initiated as soon as possible after diagnosis, including immediately at the first clinic visit if the patient is ready to commit to therapy 3, 4
• For most opportunistic infections, start ART within the first 2 weeks after diagnosis 3, 4
• Structural barriers delaying ART receipt should be removed to enable same-day initiation when appropriate 3, 4

Special Population Considerations

Patients with Renal or Bone Disease

• Avoid TDF-containing regimens in patients with or at risk for kidney disease or osteoporosis 3, 1
• TAF is preferred over TDF due to fewer renal and bone toxicities, especially when used with pharmacological boosters 1, 2

Hepatitis B Co-infection

• Use regimens containing TAF or TDF plus lamivudine or emtricitabine to ensure dual activity against both HIV and HBV 3, 1
• Avoid dolutegravir/lamivudine two-drug regimen in HBV co-infected patients 1, 4

Pregnant Patients

• Dolutegravir plus TAF/emtricitabine is the recommended regimen for pregnant individuals 3, 1
• Important considerations exist regarding potential teratogenicity of dolutegravir when initiated before conception, though current evidence supports its use 3

High Viral Load Patients

• Rilpivirine-based regimens should only be used if pretreatment HIV RNA level is <100,000 copies/mL and CD4 count is >200/μL 3
• Patients with high viral loads require potent regimens, as some combinations show suboptimal suppression in this setting 2

Regimens to Avoid for Rapid ART Start

• NNRTIs and abacavir should not be used for rapid ART initiation due to safety and resistance concerns 3

Critical Pitfalls to Avoid

Common Errors That Compromise Outcomes

• Failing to test for HLA-B*5701 before prescribing abacavir can result in life-threatening hypersensitivity reactions 1, 2
• Delaying ART initiation leads to poorer outcomes and increased HIV transmission risk 1, 4
• Overlooking drug interactions, particularly with cobicistat-boosted regimens or in patients taking rifampin for tuberculosis 1, 2
• Starting dolutegravir/lamivudine without confirming HIV RNA level <500,000 copies/mL, absence of lamivudine resistance, and no HBV co-infection 1, 4

Monitoring Protocol After Initiation

Viral Load Monitoring Schedule

• Measure viral load 4-6 weeks after starting ART to assess initial response 1, 4
• Monitor every 3 months once viral suppression is achieved, until suppression is maintained for at least 1 year 1, 4
• After 1 year of viral suppression, reduce monitoring to every 6 months 1, 4
• Regular assessment for drug-specific toxicities and adherence is essential at each visit 1, 2

Prophylaxis Considerations

Opportunistic Infection Prevention

• Primary prophylaxis for Pneumocystis pneumonia should be initiated for patients with CD4 counts below 200/μL 3
• Primary MAC prophylaxis is no longer recommended if effective ART is initiated 3
• Prophylaxis for cryptococcal disease is not recommended in highly resourced settings with low disease prevalence 3

Evidence Quality and Nuances

The recommendations prioritize InSTI-based regimens based on consistent high-quality evidence (AIa ratings) from international guidelines 3, 1, 2. While efavirenz-based regimens remain acceptable alternatives, particularly in resource-limited settings 3, 5, InSTI-based combinations demonstrate superior virologic suppression rates and tolerability 2. The shift away from NNRTI-based regimens reflects concerns about lower genetic barriers to resistance and higher rates of drug resistance development compared to NRTI-based regimens 6, 7.