Durable suppression of HIV replication is critical to (1) improving the health of infected individuals, (2) to reducing HIV transmission to sexual partners and from mothers to their infants, and (3) to maintaining the effectiveness of the current 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)- based ART. Across multiple trials, individuals with NNRTI-resistance, even at low-concentrations, have substantially greater virologic failure when treated with NVP vs. PI-ART. A cost-effective strategy is needed to detect and manage ARV-resistant HIV infections. A simple low-cost innovative assay we developed and successfully transferred to Asian and African countries (oligonucleotide ligation assay (OLA)) can detect NNRTI+lamivudine (3TC) resistant HIV using reagents that costs <$7.00/person. Furthermore, detection of NNRTI-resistance by OLA is highly (P<0.001) associated with virologic failure of nevirapine (NVP)-ART in two retrospective studies;one of Thai women who had been previously randomized to single-dose NVP and the second of ARV-na?ve Kenyan adults. Implementation of OLA into routine care we hypothesize will allow Kenyan clinicians to appropriately target protease inhibitor (PI)-based ART and improve rates of durable suppression of viral replication, and thus improve CD4 cell gains and individuals'health, reduce the transmission of ARV-resistant HIV within the community, and maintain the utility of NNRTI-ART. In addition, we hypothesize that programmatically OLA-guided ART will be more cost-efficient compared to the current strategy of empiric use of NNRTI-ART as initial treatment. Here we propose to gauge improvements in the rate of durable suppression of viral replication by ART when OLA is used to guide clinical decisions at the PEPFAR Coptic Hope Center in Kenya, and to determine the cost-effectiveness of implementing this strategy at Coptic Hope Center.
A cocktail of medicines can treat HIV infection, transforming it from a lethal to a chronic infection. HIV - resistance to these medicines appears to be increasing in Africa and can undermine treatment. An inexpensive simple assay to detect HIV drug-resistance will be implemented in Kenya. We will study the benefits conferred by this assay to improving infected individuals health, and compare the overall cost of using to not using this test.
|Silverman, Rachel A; Beck, Ingrid A; Kiptinness, Catherine et al. (2017) Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014. J Infect Dis 216:1569-1578|
|Duarte, Horacio A; Panpradist, Nuttada; Beck, Ingrid A et al. (2017) Current Status of Point-of-Care Testing for Human Immunodeficiency Virus Drug Resistance. J Infect Dis 216:S824-S828|
|Chung, Michael H; Silverman, Rachel; Beck, Ingrid A et al. (2016) Increasing HIV-1 pretreatment drug resistance among antiretroviral-naïve adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. AIDS 30:1680-2|
|Beck, Ingrid A; Payant, Rachel; Ngo-Giang-Huong, Nicole et al. (2016) Development and validation of an oligonucleotide ligation assay to detect lamivudine resistance in hepatitis B virus. J Virol Methods 233:51-5|