What are the primary care guidelines for initiating antiretroviral therapy (ART) in Human Immunodeficiency Virus (HIV) positive patients?

Primary Care Guidelines for HIV-Positive Patients

When to Start Antiretroviral Therapy

Initiate ART immediately upon HIV diagnosis for all patients who are ready to commit to treatment, regardless of CD4 count or viral load. 1 Same-day or rapid start (within 7-14 days) is strongly recommended, as this approach improves viral suppression rates, accelerates time to viral suppression, and enhances retention in care. 2

Key Timing Principles

• Universal treatment: ART is recommended for all viremic patients with established HIV infection, regardless of CD4 cell count. 1
• Immediate initiation: Start ART as soon as possible after diagnosis, including at the first clinic visit if the patient and clinician determine this is appropriate. 1
• Remove barriers: Structural barriers that delay receipt of ART should be eliminated to allow newly diagnosed persons to receive ART at the first clinic visit. 1
• Acute HIV infection: Initiate ART as soon as possible in the setting of acute HIV infection. 1

Pre-Treatment Laboratory Testing

Draw baseline labs immediately but do not delay ART initiation while waiting for results. 2 The critical exception is HLA-B*5701 testing if considering abacavir-containing regimens. 1

Required Baseline Testing

• HIV-1 RNA level (viral load) 2
• CD4 cell count 2
• HIV genotype for resistance testing 2
• Hepatitis B and C screening 2
• Basic chemistries and renal function 2
• HLA-B*5701 testing (mandatory before abacavir use; those who test positive must not receive abacavir) 1

Common Pitfall

Do not delay ART waiting for resistance testing results—treatment can be started and adjusted later if needed. 2 The only exception is HLA-B*5701 testing when using abacavir. 2

Recommended Initial ART Regimens

Preferred regimens for rapid/same-day start are integrase strand transfer inhibitor (InSTI)-based combinations that do not require baseline laboratory results beyond standard testing. 2

First-Line Regimens for Rapid Start

• Bictegravir/TAF/emtricitabine 2
• Dolutegravir plus TAF/emtricitabine 1, 2
• Raltegravir plus TAF/emtricitabine 2

Alternative First-Line Regimens (Not for Rapid Start)

• Dolutegravir/abacavir/lamivudine (requires HLA-B*5701 testing first; not recommended for rapid start) 1, 2
• Elvitegravir/cobicistat/TAF/emtricitabine 1

Second-Line Options (When InSTI Not Suitable)

• Darunavir (boosted) plus TAF/emtricitabine or abacavir/lamivudine 1
• Efavirenz/TDF/emtricitabine 1
• Rilpivirine/TAF/emtricitabine (not for rapid start due to baseline requirements) 1, 2

Regimen Selection Rationale

InSTI-based regimens are strongly preferred due to their high barrier to resistance, minimal drug interactions, excellent tolerability, and rapid viral suppression. 3, 4 Avoid NNRTIs and abacavir for same-day start due to requirements for baseline testing. 2

Renal and Bone Considerations

Tenofovir disoproxil fumarate (TDF) is not recommended for individuals with or at risk of kidney disease or bone disease (osteopenia or osteoporosis). 1 Use tenofovir alafenamide (TAF) instead in these patients. 1

Special Populations and Circumstances

Pregnancy

Pregnant individuals should initiate ART immediately for their own health and to reduce vertical transmission risk. 1, 2 Recommended regimens during pregnancy include:

• Dolutegravir 1
• Atazanavir/ritonavir 1
• Darunavir/ritonavir 1
• Raltegravir 1
• Efavirenz 1

Hepatitis B Coinfection

Patients with HIV/HBV coinfection should initiate ART containing TDF or TAF plus lamivudine or emtricitabine and a third component. 1 Entecavir may be used to treat hepatitis B but should be avoided if HIV RNA is not suppressed, as it can select for drug-resistant HIV. 1

Hepatitis C Coinfection

Patients with HIV/HCV coinfection should start an ART regimen with drugs that do not have significant drug-drug interactions with hepatitis C virus therapies. 1

Opportunistic Infections

For most opportunistic infections, initiate ART within 2 weeks of starting treatment for the opportunistic infection. 1, 3, 2 Critical exceptions include:

Tuberculosis

• CD4 <50 cells/μL: Start ART within 2 weeks of TB treatment initiation 1, 2
• CD4 ≥50 cells/μL: Start ART within 2-8 weeks of TB treatment initiation 1, 2
• Recommended regimens: Dolutegravir (50 mg twice daily), efavirenz (600 mg/day), or raltegravir (800 mg twice daily) plus 2 NRTIs 1
• Avoid: Bictegravir with rifampin due to drug-drug interactions 1
• Boosted protease inhibitors: Only if InSTI-based or efavirenz-based regimen not an option; substitute rifabutin (150 mg/day) for rifampin if possible 1

Cryptococcal Meningitis

Delay ART for 4-6 weeks after starting antifungal therapy. 1, 2, 4 Earlier initiation at 2 weeks is acceptable only for patients who have clinically improved, have controlled intracranial pressure, have negative CSF cultures, and can be closely monitored. 4 This is a critical exception—do not confuse with PCP timing. 3

Pneumocystis Pneumonia (PCP)

Initiate ART within the first 2 weeks after PCP diagnosis, as soon as the patient is clinically stable on appropriate PCP treatment and corticosteroids. 3 ART can be started as early as possible provided the patient is stable, and should not be delayed beyond day 14 of PCP treatment. 3

Malignancy

Initiate ART immediately in the setting of a new diagnosis of cancer, with attention to drug-drug interactions. 1, 2

Prophylaxis Guidelines

Pneumocystis Pneumonia (PCP)

Initiate PCP prophylaxis with TMP-SMX for patients with CD4 <200 cells/μL. 2 Continue prophylaxis even after starting ART until immune reconstitution occurs. 3

Mycobacterium Avium Complex (MAC)

MAC prophylaxis is no longer recommended if effective ART is initiated immediately. 2

Cryptococcal Disease

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

Monitoring and Follow-Up

Viral Load Monitoring

• Initial suppression: Monitor HIV RNA at baseline, 2-4 weeks after starting ART, then every 3-4 months until consistently suppressed. 1
• Goal: Achieve viral load <50 copies/mL by 24 weeks. 1
• Persistent viremia: If HIV RNA remains above the limit of quantification by 24 weeks or rebounds above 50 copies/mL, repeat assay within 4 weeks to exclude impending virologic failure. 1
• Low-level viremia: For patients with persistent quantifiable HIV RNA between 50-200 copies/mL, reassess for causes of virologic failure, evaluate again within 4 weeks, and monitor closely. 1

CD4 Cell Count Monitoring

• Baseline CD4 <200 cells/μL: Reassess every 3-4 months until viral load is reliably suppressed and CD4 count is above 350 cells/μL for 1 year, then every 6 months until virus suppressed for at least 2 years and CD4 persistently stable above 500 cells/μL. 1
• CD4 persistently >500 cells/μL: Once virus suppressed for at least 2 years and CD4 persistently above 500 cells/μL, repeat CD4 monitoring is not recommended unless virologic failure or intercurrent immunosuppressive conditions occur. 1

Renal Monitoring

Monitor for development of kidney disease with estimated glomerular filtration rate, urinalysis, and testing for glycosuria and albuminuria or proteinuria. 1 This is especially important for patients on tenofovir-containing regimens.

Immune Reconstitution Inflammatory Syndrome (IRIS)

Close monitoring during the first 2-3 months after ART initiation is essential to detect potential IRIS. 3 This is particularly important in patients with low CD4 counts and recent opportunistic infections.

Engagement in Care and Adherence

Screening and Linkage to Care

• Routine opt-out HIV screening is recommended in primary medical care settings, emergency departments, and for all pregnant women. 1
• Brief case management is recommended after HIV diagnosis. 1
• Rapid intervention following a missed clinic visit is recommended. 1

Adherence Support

• Personal telephone and interactive text reminders in advance of scheduled appointments and shortly following missed appointments (24-48 hours) are recommended. 1
• Adherence monitoring using patients' self-reports by validated adherence instruments and pharmacy refill data are recommended. 1
• Opioid substitution therapy for opioid-dependent patients is recommended. 1
• Routine screening for depression is recommended. 1

Substance Use Disorders

Integration of directly observed ART in methadone maintenance programs and as a treatment strategy among persons with substance use disorders is recommended to enhance adherence and viral suppression. 1

Prevention Considerations

Treatment as Prevention

ART is recommended for all HIV-infected individuals with detectable viremia, not only for individual health benefits but also because of the reduced infectiousness of individuals achieving virologic suppression. 1 Patients with continuously undetectable viral load on ART pose virtually no risk of transmitting infection through sexual contact. 5

Pre-Exposure Prophylaxis (PrEP)

PrEP should be considered for anyone from a population whose HIV incidence is at least 2% per year or HIV-seronegative partners of HIV-infected persons who do not have viral suppression. 1 Daily (rather than intermittent) TDF/emtricitabine is the recommended PrEP regimen. 1

Common Pitfalls to Avoid

1. Do not delay ART waiting for "complete clinical resolution" of opportunistic infections (except cryptococcal meningitis)—this increases mortality risk. 3

2. Do not use abacavir without HLA-B*5701 testing—those who test positive must not receive abacavir due to hypersensitivity risk. 1

3. Do not confuse cryptococcal meningitis timing with other opportunistic infections—cryptococcal meningitis requires 4-6 weeks delay, while most others require initiation within 2 weeks. 3, 4

4. Do not use TDF in patients with osteopenia, osteoporosis, or renal disease—use TAF instead. 1

5. Do not discontinue ART after a specific duration—planned discontinuation is not recommended outside a research setting. 1

6. Do not alter regimens for virologic blips—these are due to release of virus from chronically latently infected cells and do not require intervention in patients otherwise exhibiting viral suppression. 5