A4 Development of HIV drug resistance in HIV-infected patients failing second line regimen in Zimbabwe: A public health concern

Abstract

The countries in southern Africa are not only the most heavily impacted in the world by HIV/AIDS but are now home to the world's largest HIV/AIDS treatment programs, providing care and treatment to millions of people. As antiretroviral therapy (ART) programs in sub-Saharan Africa continue to expand, individuals on ART should be closely monitor to ensure favorable treatment outcomes and to minimize the development and transmission of HIV drug resistance, given the limited antiretroviral drug regimen choices available in these settings. We sought to investigate the frequency and determinants of virologic failure of acquired drug resistance-associated mutations (DRMs) in patients failing protease inhibitor-based antiretroviral treatment in Zimbabwe, using a prospective cohort study with cross-sectional analysis. All participants attended the HIV Clinic at Newlands Hospital-Harare and were on ART for at least twelve months. Participants with virologic failure (VL>1,000copies/ml) were tested for HIV-DRM. Demographic and clinical data were abstracted from medical records. DRMs were defined according to the Stanford HIV database guidelines. A total number of 187 plasma samples were genotyped, out of the 187 participants. Only 114 participants were on second line regimen. From the 114 participants, ART-associated PI major DRM were identified in forty-five patients (39.47 per cent) with multiclass resistance being the combination of M46I+ I50L+V82A (2.63 per cent). The most common mutations were M46I (24.77 per cent), V82A (21.43 per cent), I50L (17.70 per cent), I84A (7.08 per cent), and L90M (4.42 per cent). No PI mutations were observed in adolescents with the mean age of<20 years old and yet were prevalent in adults with mean age of>35 years old. Virologic failure rates in adults were high with the majority of ART-failing adults harboring HIV-DRM, yet in adolescents and young adults this remains an adherence problem. Viral load monitoring and drug resistance testing are urgently needed to maintain future treatment options for the millions of African living with HIV.