According to the National AIDS Control Organization (NACO), what are the recommended HIV testing protocol, first‑line antiretroviral therapy regimen (tenofovir + lamivudine + dolutegravir), baseline investigations, prophylaxis measures, viral load monitoring schedule, and criteria for switching to second‑line therapy in an adult patient?

NACO HIV Management Protocol for Adults

HIV Testing Protocol

Perform HIV testing using a fourth- or fifth-generation laboratory-based antigen-antibody assay combined with an HIV RNA (viral load) test at initial evaluation. This dual approach ensures early detection, including acute infection, before antibody seroconversion occurs. 1

• At the initial medical visit, use a rapid point-of-care test and a laboratory-based antigen/antibody combination test 1
• If HIV RNA testing is unavailable, proceed with available antigen/antibody testing and repeat at 1 month after starting therapy 1
• For persons with long-acting injectable PrEP exposure in the past 12 months, add a diagnostic HIV nucleic acid test (NAT) to the standard Ag/Ab test 1

First-Line Antiretroviral Therapy: Tenofovir + Lamivudine + Dolutegravir (TLD)

Initiate TLD (tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + dolutegravir 50 mg) as a single daily tablet immediately upon HIV diagnosis—ideally on the same day or within 7 days—regardless of CD4 count or viral load. This regimen is highly efficacious (>95% viral suppression), cost-effective, and widely used in resource-limited settings. 2, 3, 4

Key Advantages of TLD

• Single daily pill enhancing adherence 3
• High genetic barrier to resistance with dolutegravir 5, 3
• Effective even in patients with extensive NRTI resistance (>90% suppression) 6, 7, 8
• Cost-effective, particularly in low- and middle-income countries 3

Critical Contraindications and Cautions

• Avoid tenofovir disoproxil fumarate (TDF) in patients with creatinine clearance <60 mL/min or with osteopenia/osteoporosis; substitute tenofovir alafenamide (TAF) instead 1, 2, 3
• Screen for hepatitis B before initiation, as TDF/lamivudine provides dual HBV activity; discontinuation risks HBV flare 2, 3
• In pregnancy, dolutegravir-based regimens are recommended; TLD is acceptable 2, 3

Baseline Investigations (Do NOT Delay Treatment)

Draw all baseline tests before ART initiation but do not postpone treatment while awaiting results. The only exception is HLA-B*5701 testing if an abacavir-containing regimen is planned. 1, 2

Required Baseline Tests

• HIV-1 RNA viral load 1, 2
• CD4 cell count 1, 2
• Genotypic resistance testing (reverse transcriptase, protease, integrase) 1, 2
• HLA-B*5701 allele testing (only if abacavir is considered) 1, 2
• Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody 1, 2
• Complete blood count and comprehensive metabolic panel 1, 2
• Estimated glomerular filtration rate (eGFR), urinalysis for protein and glucose 1, 2
• Fasting lipid profile and glucose 1, 2
• Pregnancy test in women of childbearing potential 2

Opportunistic Infection Prophylaxis

Pneumocystis Pneumonia (PCP)

Initiate trimethoprim-sulfamethoxazole (one double-strength tablet three times weekly) for all patients with CD4 <200 cells/µL and continue until CD4 rises above 200 cells/µL for at least 3 consecutive months. 2, 3

Mycobacterium Avium Complex (MAC)

Primary MAC prophylaxis is NOT recommended when effective ART is started promptly, as early treatment sufficiently lowers MAC incidence. 2, 3

Cryptococcal Disease

Cryptococcal prophylaxis is NOT recommended in high-resource settings with low disease prevalence. 2

Viral Load Monitoring Schedule

Monitor HIV-1 RNA viral load at 4–6 weeks after ART initiation, then every 4–6 weeks until undetectable (<50 copies/mL), and subsequently every 6 months once stable suppression is achieved. 2, 3

• Goal: Undetectable viral load (<50 copies/mL) by 12–24 weeks from ART initiation 5, 3
• CD4 count monitoring: Every 6 months until >250 cells/µL for ≥1 year with viral suppression 2
• Discontinue CD4 monitoring after CD4 >500 cells/µL for 2 years with sustained viral suppression 2
• Monitor eGFR, urinalysis, and liver function tests every 6 months 1, 2

Criteria for Switching to Second-Line Therapy

Switch to second-line therapy when two consecutive viral loads are >1,000 copies/mL despite adherence counseling, or when integrase resistance is documented. 2, 5

Second-Line Regimen Selection

• Use at least two (preferably three) fully active agents from different pharmacologic classes guided by resistance testing 2
• Preferred second-line options when TLD fails:
  • Boosted darunavir (ritonavir or cobicistat) + optimized NRTIs 1, 2
  • Bictegravir-based regimen if no integrase resistance 1
• If integrase resistance develops, transition to a boosted protease inhibitor or NNRTI-based regimen 1

Management of Low-Level Viremia (50–1,000 copies/mL)

• Provide enhanced adherence counseling before switching regimens, as most patients with low-level viremia resuppress without regimen change 7, 8
• Repeat viral load in 4–6 weeks 2
• Only switch if viremia persists or increases 7, 8

Special Clinical Situations

Tuberculosis Co-infection

CD4 Count	TB Form	ART Initiation Timing	Rationale
<50 cells/µL	Non-meningeal TB	Within 2 weeks of TB therapy start	Reduces mortality [2,3]
≥50 cells/µL	Non-meningeal TB	Within 2–8 weeks of TB therapy start	Balances efficacy with IRIS risk [2,3]
Any	TB meningitis	Delay 2–4 weeks after TB treatment	Minimizes severe IRIS [2]

• For rifampin-based TB therapy, use dolutegravir 50 mg twice daily (not once daily) with two NRTIs 2, 3
• Alternative: Efavirenz 600 mg once daily or raltegravir 800 mg twice daily 2, 3

Cryptococcal Meningitis

Delay ART for 4–6 weeks after initiating antifungal therapy to lower the risk of severe immune reconstitution inflammatory syndrome (IRIS). 2, 3

Other Opportunistic Infections

Start ART within 2 weeks of beginning infection-specific therapy for most opportunistic infections (e.g., Pneumocystis pneumonia, bacterial infections). 2, 3

Common Pitfalls to Avoid

• Never delay ART while awaiting complete laboratory results (except HLA-B*5701 for abacavir); postponement eliminates the survival benefit of early treatment 1, 2
• Do not prescribe TDF to patients with CrCl <60 mL/min or osteoporosis; use TAF instead to avoid nephrotoxicity and bone loss 1, 2
• Ensure twice-daily dosing of lamivudine/zidovudine combinations if used; once-daily dosing leads to subtherapeutic levels and virologic failure 5
• Do not add a single active agent to a failing regimen; always switch to at least two fully active drugs from different classes 5
• In patients with low-level viremia (<1,000 copies/mL), intensify adherence support before switching regimens, as most will resuppress without regimen change 7, 8