Improving Diagnosis, Treatment & Detection of Drug Resistance in HIV-2 Infection

To achieve the UNAIDS 95-95-95 targets, and to eventually end the HIV/AIDS pandemic by 2030, simple, safe, and effective antiretroviral (ARV)-regimens are needed, as well as simple and inexpensive, point-of-care devices for HIV viral load monitoring and “real-time” access to drug resistance testing in those with virologic failure. The global rollout of a 1st-line dolutegravir (DTG)-based antiretroviral therapy (ART) with a generic, single-tablet regimen of tenofovir-lamivudine-dolutegravir (TLD) has the potential to significantly alter the course of the HIV/AIDS epidemic in resource-limited settings (RLS). However, as of the end of 2022, in West/Central Africa, home to ~4.8 million people with HIV (PWH), with ~160,000 new infections and ~120,000 deaths per year, the UNAIDS 95-95-95 targets are lagging (80%, 76%, 69%). In West Africa, progress towards the goal of an HIV- free generation is complicated by the fact that both HIV-1 and HIV-2 are co-circulating, each with its’ own challenges for diagnosis, ART and clinical management. Since 2020, 1st-line ART for HIV-1, HIV-2 and dual HIV- 1/HIV-2 infection has been TLD and rollout of TLD in West Africa has had the potential to dramatically improve the treatment landscape by providing a single potent ART regimen for all PWH including those living with HIV-1, HIV-2 or HIV-1/HIV-2 dual infection. However, the long term effectiveness of TLD for HIV-2 and HIV-1/HIV-2 dual infection is unproven, and early data has shown the emergence of multidrug, DTG-resistant (MDR) HIV-2 in persons failing DTG-based regimens. Novel agents, including long-acting antiretrovirals, are needed to treat HIV-2, including people with HIV-2 (PWH2) with MDR virus, which is an emerging problem not only in West Africa but also in the United States, Europe and other locales where HIV-2 is circulating. There are critical gaps in the care, management and treatment of people with HIV-2, especially those with virologic failure and multidrug resistant HIV-2. The University of Washington-Senegal Research Collaboration has a greater than three decade history of performing cutting-edge translational and clinical studies of HIV-2 care and treatment with our Senegalese partners. For the Renewal of our current R01(AI120765) entitled “Improving Diagnosis, Treatment & Detection of Drug Resistance in HIV-2 Infection” we propose to build on our previous work with the following innovative SPECIFIC AIMS: AIM 1: A cohort study of long term clinical and immuno-virologic outcomes in people living with HIV-2 and HIV-1/HIV-2 dual infection who have initiated dolutegravir- based ART (TLD) in the Senegal National HIV/AIDS Treatment Program. AIM 2: Determination of genotypic and phenotypic susceptibility, resistance mechanisms and pathways, of HIV-2 to novel and pipeline antiretroviral agents. Our overarching goals are to improve care, management and treatment of people with HIV-2.