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Project

HIV-1 drug resistance: prevalence in Tanzania, determinants of drug resistance and impact of interventions on treatment outcomes

In total approximately 1,550,000 people are living with HIV (PLHIV), of those 1,126,366 (75%) are enrolled into HIV care and treatment and out of those, 1,103,016 (98%) are on antiretroviral treatment (ART). ART programs in developing countries, including Tanzania, are now advocating a test and treat strategy (National AIDS Control Programme, 2019). However, the long-term challenges of scaling up ART will include drug toxicities, treatment failure and emergence of drug resistance (John R.Giudicessi, 2013). Especially HIVDR is compromising the capacity to reach the last 90 of the 90-90-90 targets. Evidence from a recent study conducted in children and adolescents in rural Tanzania found that, among 213 children enrolled in the study, 25.4% failed virologically, ART associated drug resistance mutations (DRMs) were identified in 90%, with multiclass resistance of 79%. Furthermore, these findings suggested that more than 85% had acquired key DRMs during treatment (Muri et al., 2017). Another study, conducted in Dar es Salam, revealed pre-treatment DRMs in 29.8% ART naïve patients. Of these, 14.9% harbored mutations that confer high-level resistance to at least one drug of the default first-line regimen (Barabona et al., 2019).

Dar es Salam has an Urban Cohort Study, [ (DUCS) (http://www.aaph-tz.org/activities/dar-es-salaam-urban-cohort-study-ducs)], which was initiated in 2011 to establish and maintain a Demographic Surveillance System (DSS) that will monitor health and socio-demographic events over time in Dar es Salaam, Tanzania. The platform was developed in partnership between the Harvard T.H. Chan School of Public Health and Muhimbili University of Health and Allied Sciences (MUHAS). The surveillance site covers a population of approximately 100,000 residents living in close to 20,000 households in the Ukonga and Gongolamboto wards of Ilala district in Dar es Salaam. More importantly, the DUCS cohort is also being used by two VLIR-IOS projects (see local activities below). the VLIR-SI project supports capacity building at MUHAS for including HIV status and HIV drug resistance testing among the monitored variables in the cohort. It also develops a transdisciplinary approach to build a conceptual model for preventing the development of HIVDR. The VLIR-UOS JOINT project is identifying intervention measures to prevent the development of HIVDR using the conceptual model, and identifying Key Performance Indicators (KPIs) to follow-up the impact of the intervention measures.

Although several studies on ART resistance in Tanzania have been published (Ramadhani et al., 2007; Somi et al., 2008; Kasang et al., 2011; Mosha et al., 2011; Vairo et al., 2013), the majority did not apply interventions to achieve sustained suppression of viral replication and thus avoid resistance, thereby compromising the long-term benefit of ART. For the purpose of generating research evidence so as to advise the existing guidelines and policies in Tanzania, we propose the here described study. We aim to i) determine the current prevalence of HIV drug resistance (HIVDR) following the scaled up use of ART, ii) set up a sustainable protocol of measuring key performance indicators in order to be able to assess the impact of interventions that aim to reduce the prevalence of HIVDR. Such interventions are currently being developed through a transdisciplinary and human/patient centered approach supported by 2 VLIR-UOS projects that are currently running up to end of 2021.

Date:2 Oct 2020 →  Today
Keywords:Tanzania, Key performance indicators, Transdisciplinary approach, Anti-retroviral resistance, Anti-HIV drugs resistance
Disciplines:Clinical microbiology, Virology, Epidemiology, Analysis of next-generation sequence data
Project type:PhD project