# HIV-2 Infection

HIV-2 requires deliberate recognition, type-specific viral-load access, and regimens active against HIV-2. Although progression and transmission are generally slower than with HIV-1, untreated infection can cause AIDS; avoid NNRTIs and coordinate care with an experienced HIV-2 clinician.

**Clinical question:** How should U.S. clinicians diagnose, treat, and monitor adults with HIV-2 infection or HIV-1/HIV-2 coinfection?

Updated: 2026-08-20T23:47:28.059827Z

## What matters in practice
- Use the standard laboratory HIV algorithm: a reactive HIV-1/2 antigen-antibody assay followed by an HIV-1/HIV-2 antibody differentiation immunoassay. HIV-2 antibody positivity establishes HIV-2 serologic diagnosis. [20]
- Do not use NNRTIs, including long-acting cabotegravir/rilpivirine, for HIV-2 because NNRTIs lack activity against HIV-2. [20]
- Initiate ART for all patients with HIV-2; preferred initial therapy is 2 NRTIs plus an INSTI, typically tenofovir alafenamide/emtricitabine/bictegravir or tenofovir/emtricitabine plus dolutegravir. [20]
- HIV-2 quantitative viral-load and resistance testing are not commercially available in the United States; maintain CD4 monitoring every 6 months even with viral suppression and seek expert consultation for suspected failure. [20]

## Recognize HIV-2 when subtype changes management

HIV-2 is uncommon in the United States but has major treatment implications.

HIV-2 is endemic in West Africa and remains rare in the United States. In U.S. surveillance from 2010 through 2017, 102 of 327,700 HIV diagnoses were confirmed HIV-2 and 11 were dual HIV-1/HIV-2 infections. HIV-2 is associated with lower plasma viral loads, slower progression, and less efficient sexual and perinatal transmission than HIV-1; however, untreated patients can develop opportunistic infections, AIDS, and death. [20]

Promptly review country of birth, prior residence, partners, and exposure networks connected to West Africa. HIV-2 should also be considered when clinical progression or declining CD4 count is discordant with an undetectable HIV-1 RNA result, particularly in a person with epidemiologic exposure risk. [20]
- Do not infer benign disease from a low or unquantifiable HIV-2 RNA level; progression has been reported despite undetectable HIV-2 viral load. [20]
- Evaluate and manage opportunistic infections and prophylaxis using the same clinical framework used for HIV-1. [20]

## Confirm HIV-2 and resolve discordant results

Use the standard HIV diagnostic sequence, then ensure type-specific interpretation.

Testing begins with an FDA-approved HIV-1/2 antigen-antibody combination immunoassay, which detects HIV-1 p24 antigen and antibodies to HIV-1 and HIV-2 but does not detect HIV-2 antigen. A reactive screen is followed by an FDA-approved HIV-1/HIV-2 antibody differentiation immunoassay. [20]

If the differentiation assay is nonreactive or indeterminate for HIV-1 and/or HIV-2 antibodies, obtain HIV-1 RNA nucleic acid testing to confirm or exclude acute HIV-1 infection. A negative HIV-1 RNA test does not exclude very recent HIV-2 acquisition; with a negative initial antigen-antibody assay but suspected recent HIV-2 exposure, obtain expert or public-health laboratory input for HIV-2-specific testing. [20]

*Interpretation of the HIV laboratory algorithm for suspected HIV-2. [20]*

| Test pattern | Interpretation and next action |
| --- | --- |
| Reactive HIV-1/2 antigen-antibody assay; HIV-2 antibody positive only on differentiation assay | HIV-2 antibody positive; perform a full HIV baseline evaluation and arrange HIV-2 viral-load access. [20] |
| Reactive HIV-1/2 antigen-antibody assay; both HIV-1 and HIV-2 antibodies positive | HIV-positive but undifferentiated; evaluate for HIV-1/HIV-2 coinfection and select a regimen active against both viruses. [20] |
| Reactive screening assay; differentiation assay nonreactive or indeterminate | Order HIV-1 RNA NAT to evaluate acute HIV-1 infection. [20] |
| Nonreactive screening assay with recent exposure risk for HIV-2 | Do not dismiss suspected early HIV-2; obtain HIV-2-specific testing guidance from an experienced clinician or laboratory. [20] |

## Stage disease and establish a monitoring pathway before or alongside ART

Do not delay ART while arranging HIV-2-specific testing.

Perform baseline assessment comparable to that for HIV-1, including CD4 count, HIV-2 viral load where available, creatinine clearance, and assessment for hepatitis B, hepatitis C, and tuberculosis coinfection. HIV-2 resistance testing is not commercially available in the United States. [20]

ART is recommended for all patients with HIV-2, including those with low-level or unquantifiable viremia. The absence of commercial resistance testing and limited treatment evidence increase the value of early expert HIV-2 consultation, especially for prior ART exposure, suspected treatment failure, pregnancy, or HIV-1/HIV-2 coinfection. [20]
- Obtain HIV-1 genotypic resistance testing in confirmed HIV-1/HIV-2 coinfection; choose therapy that suppresses both viruses. [20]
- For patients with suspected acute HIV-2, do not wait for HIV-2 viral-load access before initiating an HIV-2-active regimen. [20]

## Use an HIV-2-active regimen and avoid inactive drug classes

INSTI-based triple therapy is preferred for treatment-naive adults.

Preferred initial treatment for nonpregnant adults is a regimen containing 2 NRTIs plus an INSTI. Recommended options include tenofovir alafenamide/emtricitabine/bictegravir as a single tablet or tenofovir alafenamide/emtricitabine or tenofovir disoproxil fumarate/emtricitabine plus dolutegravir. In the cited guideline, FTC and lamivudine are interchangeable; tenofovir-based regimens should not be initiated when creatinine clearance is below 30 mL/min. [20]

Do not prescribe NNRTIs for HIV-2, including injectable rilpivirine with cabotegravir. HIV-2 also has no or greatly reduced susceptibility to atazanavir, fosamprenavir, tipranavir, and nelfinavir; if a protease inhibitor is needed, boosted darunavir is preferred. [20]

Evidence supporting HIV-2 therapy is substantially less robust than for HIV-1. In a phase 2 study, 27 of 30 treatment-naive patients receiving dolutegravir plus 2 NRTIs achieved HIV-2 RNA below 40 copies/mL at week 48. Observational data also support INSTI-based approaches, but these studies do not establish comparative superiority among all recommended options. [20]

### Alternative regimens and key selection constraints

Alternative regimens include tenofovir/emtricitabine with raltegravir, high-dose raltegravir, or darunavir/ritonavir; tenofovir alafenamide/emtricitabine/darunavir/cobicistat and tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat are listed as alternatives. Cobicistat-containing regimens require careful review for drug interactions. [20]
- Avoid dolutegravir/lamivudine dual therapy for HIV-2 because resistance testing is unavailable and the regimen requires confidence that M184V is absent. [20]
- If HIV-2 is acquired during long-acting cabotegravir PrEP, select a non-INSTI-based initial regimen, such as boosted darunavir plus 2 NRTIs, while expert evaluation proceeds. [20]
- Separate bictegravir or dolutegravir from magnesium- or aluminum-containing antacids: administer the antacid 2 hours before or 6 hours after the INSTI; calcium or iron may be coadministered with food. [20]

*Initial ART choices for nonpregnant adults with HIV-2. [20]*

| Regimen | Clinical use and constraints |
| --- | --- |
| TAF 25 mg/FTC/BIC | Preferred single-tablet INSTI regimen; do not initiate a tenofovir-based regimen if creatinine clearance is below 30 mL/min. [20] |
| TAF/FTC or TDF/FTC plus dolutegravir | Preferred; TAF/FTC is strongly preferred over TDF/FTC when creatinine clearance is below 50 mL/min. For TDF/FTC with creatinine clearance 30 to 49 mL/min, the cited guideline specifies 1 tablet every 48 hours. [20] |
| TAF/FTC or TDF/FTC plus darunavir/ritonavir | Alternative when an INSTI is unsuitable or after INSTI failure; review boosted-PI interactions. [20] |
| Any NNRTI-containing regimen | Do not use for HIV-2 because the class lacks HIV-2 activity. [20] |

## Monitor HIV-2 with viral load when possible and CD4 count regardless

A suppressed viral load does not eliminate the need for immunologic follow-up.

No FDA-approved commercial quantitative HIV-2 viral-load assay is available in the United States. The New York State Wadsworth Center provides HIV-2 RNA testing, but clinicians outside New York may need referral or specialized laboratory arrangements. Monitor HIV-2 viral load and CD4 count at the same intervals used for HIV-1, and continue CD4 testing at least every 6 months even when HIV-2 viral load remains suppressed. [20]

If HIV-2 viral load is unavailable, suspect treatment failure with a sustained 30% decline in CD4 count or a 3-point decline in CD4 percentage, confirmed on repeat testing, or with clinical progression. A blunted CD4 increase after ART initiation may occur in HIV-2 and does not alone establish regimen failure. [20]

For confirmed virologic or immunologic failure, reassess adherence and drug interactions, then consult an experienced HIV-2 specialist. In the absence of HIV-2 resistance testing, failure on an INSTI-based regimen generally favors switching to an active boosted protease inhibitor-based regimen; failure on a boosted PI regimen generally favors an INSTI-based regimen. [20]
- Do not rely solely on HIV-1 RNA assays for HIV-2 treatment monitoring. [20]
- Avoid serial within-class substitutions without expert input because HIV-2 resistance and cross-resistance can limit remaining options. [20]

## Pregnancy and postexposure management require HIV-2-active therapy

Prevent perinatal transmission while avoiding regimens with poor HIV-2 activity or inadequate pregnancy exposure.

ART is recommended for all pregnant patients with HIV-2 and should not be delayed for HIV-2 viral-load availability. Preferred listed regimens are tenofovir alafenamide/emtricitabine/bictegravir or tenofovir alafenamide/emtricitabine, tenofovir disoproxil fumarate/emtricitabine, or tenofovir disoproxil fumarate/lamivudine plus dolutegravir. [20]

Avoid boosted atazanavir and NNRTIs such as efavirenz and rilpivirine because of inadequate HIV-2 activity. Avoid elvitegravir/cobicistat and darunavir/cobicistat during pregnancy because of concern for lower third-trimester drug exposure. [20]

For HIV-2 exposure, the cited New York guideline recommends tenofovir alafenamide/emtricitabine/bictegravir as PEP. Alternatives are tenofovir alafenamide/emtricitabine or tenofovir disoproxil fumarate/emtricitabine with dolutegravir or raltegravir; lamivudine may substitute for emtricitabine. [20]

## Common questions

### Is HIV-2 less serious than HIV-1?

HIV-2 generally has lower plasma viral load, slower progression, and less efficient sexual and perinatal transmission than HIV-1, but untreated infection can progress to opportunistic disease, AIDS, and death. [20]

### Can long-acting cabotegravir/rilpivirine treat HIV-2?

No. Rilpivirine is an NNRTI, and NNRTIs are not active against HIV-2; the cited guideline specifically advises against long-acting cabotegravir/rilpivirine for HIV-2 treatment. [20]

### What should prompt HIV-2 expert consultation?

Consult for suspected or confirmed treatment failure, prior ART exposure, pregnancy, uncertain HIV-1/HIV-2 coinfection, or lack of access to HIV-2 viral-load testing. U.S. HIV-2 resistance testing is not commercially available. [20]

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## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.