Is there a treatment for Acquired Immune Deficiency Syndrome (AIDS)?

Treatment for AIDS

Yes, there is highly effective treatment for AIDS—antiretroviral therapy (ART) should be initiated immediately for all HIV-infected individuals with detectable plasma virus, regardless of CD4 count, using an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs) as the preferred regimen. 1, 2

When to Start Treatment

• Immediate initiation is recommended: ART should be started as soon as possible after HIV diagnosis, ideally within 7 days, and same-day initiation is feasible when resources permit 2
• Universal treatment approach: All HIV-infected individuals with detectable plasma virus should receive ART regardless of CD4 cell count 3, 2
• For acute HIV infection: Immediate ART is strongly recommended due to urgent need for viral suppression 2
• Treatment benefits: ART has revolutionized HIV care since 1996, leading to dramatic reductions in mortality worldwide and transforming HIV from a fatal disease to a manageable chronic condition 3

Preferred First-Line Regimens

The optimal initial regimen consists of an InSTI plus 2 NRTIs 1, 2:

Specific Recommended Combinations:

• Bictegravir-based regimens: Bictegravir with tenofovir alafenamide (TAF)/emtricitabine—approved in 2018 with high barrier to resistance and low pill burden 1
• Dolutegravir-based regimens: Either dolutegravir/abacavir/lamivudine OR dolutegravir plus TAF/emtricitabine 1, 2
• Raltegravir-based regimens: Raltegravir plus TAF/emtricitabine 2

Why InSTIs Are Preferred:

• Superior efficacy with comparable results showing no emergence of resistant virus in initial treatment studies 1
• Better tolerability with fewer adverse effects than older drug classes 1
• Higher genetic barrier to resistance 1
• No pharmacologic boosting required 1
• Low pill burden and toxicity profile 1

NRTI Backbone Options

• Tenofovir-based backbones: Either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) combined with emtricitabine or lamivudine 1
• TAF advantages: Results in lower plasma tenofovir levels but higher intracellular concentrations compared to TDF, with similar virologic efficacy 1
• Abacavir/lamivudine alternative: Can be used particularly with dolutegravir, but mandatory HLA-B*5701 testing must be performed before use to avoid potentially fatal hypersensitivity reactions 1, 2

Alternative Regimens (When InSTIs Cannot Be Used)

• NNRTI-based regimens: Efavirenz or rilpivirine combined with 2 NRTIs demonstrate high virologic suppression rates but have more adverse effects than InSTI-based regimens 1
• Rilpivirine restrictions: Must be taken with food and only recommended for patients with baseline HIV RNA <100,000 copies/mL and CD4 count >200/μL 1
• Doravirine: Shows non-inferiority to efavirenz with fewer central nervous system adverse events 1
• Boosted protease inhibitors: Darunavir/ritonavir combined with 2 NRTIs are effective but have more side effects and drug interactions 1

Treatment Goals and Expected Outcomes

• Primary goal: Suppression of plasma viremia to undetectable levels (<50 copies/mL) as much as possible for as long as possible 3, 4
• CD4 count recovery: HAART typically leads to increases in CD4+ T cell count of ≥100-200 cells/mm³, though responses vary 3
• Survival outcomes: With current ART regimens, survival rates among HIV-infected adults retained in care can approach those of uninfected adults 2
• Transmission prevention: ART reduces viral load in blood, semen, and genital tract, thereby reducing HIV transmission to sexual partners 3

Monitoring Treatment Response

• Initial viral load testing: Within 4-6 weeks of starting ART 2
• Ongoing monitoring until suppression: Every 3 months until viral load is <50 copies/mL for at least 1 year 1, 2
• Long-term monitoring: Every 6 months once suppressed for at least a year with consistent adherence 1, 2
• CD4 monitoring: Every 6 months until counts are above 250/μL for at least 1 year with viral suppression 2

Critical Safety Considerations and Pitfalls

Before Starting Treatment:

• Genotype resistance testing: Should be performed before initiating therapy to guide regimen selection 1
• HLA-B*5701 testing: Mandatory before abacavir use; positive patients must not receive abacavir 1, 2
• Hepatitis B testing: All HIV patients should be tested for chronic hepatitis B before starting treatment 5
• Renal function assessment: Baseline serum creatinine, estimated creatinine clearance, urine glucose, and urine protein should be assessed 5

Drug-Specific Warnings:

• Tenofovir (TDF) renal toxicity: Can cause acute renal failure and Fanconi syndrome; avoid in patients with creatinine clearance <50 mL/min or concurrent nephrotoxic agents (especially NSAIDs) 5
• Tenofovir bone effects: Associated with decreased bone mineral density and increased bone turnover; consider BMD assessment in patients with fracture history or osteoporosis risk factors 5
• Hepatitis B co-infection: Avoid abacavir-based regimens as abacavir has no activity against hepatitis B virus 1
• Severe hepatitis exacerbation: Can occur upon discontinuation of tenofovir in patients with HIV/HBV co-infection; close monitoring required for several months after stopping 5

Special Populations:

• Pregnancy: Tenofovir is present in breast milk; HIV-infected mothers should not breastfeed to avoid postnatal HIV transmission 5
• Pediatric patients: Safety and effectiveness established for ages 2 years and older; effects on long-term bone health in children remain unknown 5
• Tuberculosis co-infection: Start ART within 2 weeks after tuberculosis treatment initiation if CD4 count <50 cells/μL 2
• Cryptococcal meningitis: Delay ART for 4-6 weeks after antifungal therapy initiation 2

Adherence: The Critical Success Factor

• Adherence is crucial: Systematic monitoring of ART adherence is essential for successful treatment 2
• Predictors of success: Adherence to the drug regimen is one of the strongest predictors of virologic success 3
• Support strategies: Integration of directly observed ART in methadone maintenance programs is recommended for persons with substance use disorders 2
• Long-acting options: Injectable formulations of cabotegravir (InSTI) and rilpivirine (NNRTI) administered intramuscularly every 4-8 weeks are available for patients with adherence challenges 3, 1

Managing Treatment Failure

• If viral load has not declined: First assess adherence and medication tolerability 2
• If adherence is adequate but suppression not achieved: Perform genotypic resistance testing 2
• Rescue regimens: Should include three (or at least two) drugs that are fully active against HIV 4

Immune Reconstitution Considerations

• Immune reconstitution inflammatory syndrome (IRIS): Can occur in HIV-infected patients treated with combination ART as the immune system responds to indolent or residual opportunistic infections (Mycobacterium avium, cytomegalovirus, Pneumocystis jirovecii pneumonia, tuberculosis) 5, 6
• Autoimmune disorders: Graves' disease, polymyositis, and Guillain-Barré syndrome can occur with immune reconstitution, often many months after treatment initiation 5
• Early treatment benefits: Early ART can prevent AIDS-associated events, restrict cell subset imbalances and dysfunction, and preserve structural integrity of lymphoid tissues 6

Current Limitations and Future Directions

• Not a cure: Current ART is highly effective but incurable; patients require lifelong medication 3, 7, 8
• Challenges of lifelong therapy: Include stigma, pill burden, side effects, and risk of viral resistance with non-compliance 7
• Cure research ongoing: Two potential cure strategies are being investigated: (1) functional cure where patients control infection without therapy, and (2) eradication cure where all replication-competent virus is purged 3
• Emerging therapies: Include broadly neutralizing antibodies, gene therapy, and therapeutic vaccines, though these require more development before widespread use 3