Dolutegravir-Based ART — Effective for HIV-2 Infection

In a small single-arm, open-label trial in Portugal, dolutegravir + two NRTIs proved effective and safe for managing HIV-2 infection.

Data are sparse regarding treatment of HIV-2 infection with contemporary ART regimens; moreover, HIV-2 exhibits intrinsic resistance to NNRTIs. Further complicating the management of HIV-2 infection is the fact that plasma HIV-2 RNA levels, when available, typically run very low (often undetectable) compared with HIV-1 levels, often resulting in reliance on CD4 count and clinical assessment to gauge response to ART. Previously, two small studies demonstrated that a first-generation INSTI-based regimen (raltegravir or elvitegravir) was generally effective — but in each study, a case of virologic failure with INSTI resistance occurred. Now, Pacheco et al. (supported by a grant from ViiV Healthcare) have evaluated week-48 responses to a dolutegravir-based regimen among treatment-naive persons in Portugal living with HIV-2 infection (PWHIV-2) and baseline CD4 count ≤500 cells/mm3.

Baseline median age of the 30 enrolled participants was 55; 22 were women, 25 were African born, 17 were viremic (median, 190 copies/mL) with median CD4 count of 483 cells/mm3 and CD4/CD8 ratio of 0.8. The background NRTI regimen consisted of either abacavir/lamivudine (21 participants) or tenofovir DF/emtricitabine (9 participants). Twenty-seven participants completed the study (withdrawals were due to adverse CNS side effects, loss to follow-up, or participant request). For those who completed the study, at week 48 all had HIV-2 levels <40 copies/mL with mean changes in CD4 count of +96 cells/mm3 and CD4/CD8 ratio of +0.32. The ART regimen was judged to be safe and well tolerated.

COMMENT

As an editorialist notes, ART utilizing tenofovir/lamivudine/dolutegravir has been recommended as first-line treatment for HIV-2 or dual HIV-1/HIV-2 since 2018 (based on extrapolation from in vitro data and scant clinical data). Identification and subsequent quantification of HIV-2 infection (including resistance testing) remains problematic, even in the U.S. This study and editorial provide reassurance about second-generation INSTI-based therapy for HIV-2 infection, while highlighting the need for expanded access to laboratory tools and more clinical data on globally available contemporary ART regimens.

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Published: October 27, 2023