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

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The UNAIDS has set ambitious “90-90-90” targets (90% of all people living with HIV will know their HIV status, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy, 90% of all people receiving antiretroviral therapy will have viral suppression) and an end to the AIDS epidemic by 2030. To achieve these goals, and to eventually end the HIV epidemic, simple, safe, effective and potent ARV-regimens will be needed as well as simple and inexpensive, point-of-care devices for HIV diagnosis and viral load monitoring. The planned global rollout of a 1st-line dolutegravir based ART with a generic, single table regimen of tenofovir- lamivudine-dolutegravir (TLD) with an estimated cost of $75 (USD)/year has the potential the dramatically alter the course of the AIDS epidemic in resource limited settings (RLS). In West/Central Africa, home to ~5.0 million people living with HIV (PLHIV), ~280,000 new infections and ~160,000 deaths per year, and lagging 90-90-90 targets (64%, 51%, 39%) the goal of an AIDS free generation is complicated by the fact that both HIV-1 and HIV- 2 are co-circulating in West Africa, each with its’ own challenges for diagnosis and antiretroviral treatment (ART). Currently, 1st-line ART for HIV-2 (and dual HIV-1/HIV-2 infection) is tenofovir-lamivudine-lopinavir/ritonavir due to HIV-2’s intrinsic resistance to NNRTI. Rollout of TLD in West Africa has the potential to dramatically alter the treatment landscape by providing a single potent 1st-line ART regimen for both HIV-1 and HIV-2. The Senegal National AIDS Program (Initiative Senegalaise d’Acces aux ARV (ISAARV)) is planning for the transition to TLD for 1st line ART for HIV-1, HIV-2 and HIV-1/HIV-2 dual infections in early 2020. The UW-Senegal Research Collaboration has a 3 decades history of performing cutting edge translational and clinical studies of HIV-2 treatment with our Senegalese partners. For the Renewal of our current R01 entitled “Improving Diagnosis, Treatment & Detection of Drug Resistance in HIV-2 Infection” we propose to build on our previous work with the following Specific Aims: AIM 1: To determine the clinical and immuno-virologic outcomes (HIV virologic failure(VF)/viral suppression (VS) rates, HIV drug resistance (DR), CD4 counts, switch rates to 2nd-line ART, adverse events, OIs & co-morbidities, LTFU and death), in ARV-naïve and ARV-experienced HIV-2 and HIV-1/HIV-2 infected patients, newly initiated on dolutegravir-based ART (TLD) in the ISAARV program. AIM 2: Determination of genotypic and phenotypic susceptibility, resistance mechanisms and pathways, of HIV-2 to novel and pipeline antiretroviral agents. AIM 3: 3A: Validation & field evaluation of the POC m-PIMA HIV-1/2 Viral Load (VL) & Detect Assays in Senegal. 3B: An implementation trial of m- PIMA clinical uptake & utilization for patient care decisions regarding HIV-2 & HIV-1/HIV-2 VF & ART management in the ISAARV.