What is the primary treatment for Human Immunodeficiency Virus (HIV)?

Treatment for HIV

The primary treatment for HIV is combination antiretroviral therapy (ART) consisting of an integrase strand transfer inhibitor (INSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs), with bictegravir or dolutegravir as the preferred INSTIs due to their high barrier to resistance, lack of need for pharmacologic boosting, and low pill burden. 1, 2

Recommended First-Line Regimens

Preferred initial regimens include:

• Bictegravir + tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) + emtricitabine or lamivudine 1, 2
• Dolutegravir + TAF or TDF + emtricitabine or lamivudine 1, 2, 3
• Dolutegravir + abacavir + lamivudine (requires HLA-B*5701 testing before use to avoid hypersensitivity reactions) 1, 2

These INSTI-based regimens have demonstrated comparable efficacy with no emergence of resistant virus in initial treatment studies and are associated with minimal toxicity 2, 1.

Alternative Regimens When First-Line Options Are Not Suitable

If INSTI-based regimens cannot be used:

• Efavirenz (NNRTI) + 2 NRTIs demonstrates high rates of virologic suppression but has more central nervous system adverse effects 1, 4
• Rilpivirine (NNRTI) + 2 NRTIs has fewer CNS effects than efavirenz but requires administration with food and is only appropriate for patients with baseline HIV RNA <100,000 copies/mL and CD4 count >200/μL 1
• Boosted protease inhibitors (darunavir/ritonavir) + 2 NRTIs are effective but have more side effects and drug interactions 1

When to Initiate Treatment

ART should be initiated immediately upon HIV diagnosis for all infected patients, regardless of CD4 count or viral load. 5, 2

• For most ambulatory patients committed to starting ART, treatment initiation is recommended as soon as possible, including rapid start on the day of diagnosis when feasible 2
• For patients with active opportunistic infections (except cryptococcal meningitis), ART should begin within the first 2 weeks after diagnosis 2
• For tuberculosis co-infection, start ART within 2 weeks for CD4 <50/μL and within 2-8 weeks for CD4 ≥50/μL 2

Pre-Treatment Testing Requirements

Before initiating ART, perform:

• HIV RNA (viral load) level 5
• CD4 cell count with percentage 5
• Genotypic resistance testing 1, 5
• HLA-B*5701 testing (if considering abacavir) 2, 1
• Hepatitis B and C screening 5
• Renal function (creatinine clearance) 6
• Pregnancy test in persons of childbearing potential 5

Monitoring During Treatment

Viral load monitoring schedule:

• Measure HIV RNA at 4-6 weeks after starting ART to assess initial response 2, 1
• Every 3 months until viral load <50 copies/mL for 1 year 2, 1
• Every 6 months thereafter once sustained suppression is achieved 2, 1

CD4 count monitoring:

• Every 6 months until counts are >250/μL for at least 1 year with concomitant viral suppression 2, 5

If viral load remains detectable:

• Repeat measurement within 4 weeks 2
• Reassess medication adherence and tolerability 2
• If adherence appears sufficient, perform genotypic resistance testing 2, 5

Treatment Goals

The primary goal of ART is maximal and durable suppression of viral load to below 50 copies/mL. 2

• Eradication of HIV infection cannot be achieved with currently available antiretroviral regimens due to latently infected CD4+ T cells that persist even with prolonged viral suppression 2
• Secondary goals include restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality 2

Critical Considerations and Common Pitfalls

Hepatitis B co-infection: Avoid abacavir-based regimens as abacavir has no activity against HBV; use tenofovir-containing regimens instead 1, 6

Renal impairment: TDF should be avoided or dose-adjusted if creatinine clearance <60 mL/min; TAF is preferred in this setting 1, 6

Drug interactions: Carefully review all concomitant medications, particularly when using boosted protease inhibitors 1

Adherence: Long-acting injectable formulations (cabotegravir + rilpivirine administered intramuscularly every 4-8 weeks) may be considered for patients with adherence challenges, though comprehensive strategies are still needed to avoid delayed or missed doses 2, 1

Resistance concerns: Any regimen that is not expected to maximally suppress viral replication should not be used, as suboptimal suppression leads to resistance development and limits future treatment options 2

Emerging Treatment Options

Long-acting injectable ART (cabotegravir + rilpivirine) has demonstrated efficacy in maintaining virologic suppression when given monthly or every 8 weeks, potentially reducing the burden of daily oral therapy 2, 1