Prevalence of Genotypic Resistance to Antiretroviral Drugs in Treatment-Naive Youths Infected with Diverse HIV Type 1 Subtypes and Recombinant Forms in Dar es Salaam, Tanzania

Abstract

As human immunodeficiency virus (HIV) diversity may have an impact on both vaccine efficacy and drug resistance, it is important to have knowledge of circulating genetic variants. With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. This study aimed to determine the circulating HIV subtypes and recombinant forms, as well as the prevalence of ARV drug resistance mutations, among 75 treatment-naive HIV-infected youths in Dar es Salaam, Tanzania. Gag (n = 48), partial pol (n = 44), and partial env (n = 35) sequencing was performed; all three regions were sequenced in 26 samples. Evidence of infection with recombinant viruses was found in 12 (46%) participants; AC recombinants were the most commonly detected and they were identified in six (23%) participants. Of individuals infected with nonrecombinant strains, subtype A was most commonly detected in seven (27%) participants, followed by subtype C detected in six (23%) participants and subtype D detected in one (4%) participant. Among the pol sequences from 44 individuals, three (7%) had resistance to nucleoside reverse transcriptase (RT) inhibitors and four (9%) had nonnucleoside RT inhibitor resistance mutations. Of these, three (7%) individuals were infected with viruses with cross-resistance mutations to both classes of RT inhibitors. These resistant mutations were all associated with drugs currently used in first-line therapy and in the prevention of vertical transmission. This high prevalence of resistance mutations is of considerable concern in apparently drug-naive populations as it may result in treatment failure and the spread of ARV-resistant strains.

Prevalence of Drug Resistance Mutations and HIV Type 1 Subtypes in an HIV Type 1-Infected Cohort in Rural Tanzania

“…Despite little prior availability of ART in the study area some primary resistances, i.e., new infections with a drug-resistant strain, had to be expected to occur according to reports from other areas in Tanzania. 12,16 In Tanzania the prevention of mother-to-child transmission (PMTCT) of HIV-1 policy (2009) recommends combination regimens that include zidovudine (AZT), nevirapine (NVP), and lamivudine (3TC) in areas with the capacity to offer and monitor ART. For all other areas with no such capability the policy recommends only the use of minimum antiretroviral prophylaxis consisting of a single dose of nevirapine to the mother and the infant.…”

Strengthening HIV therapy and care in rural Tanzania affects rates of viral suppression

“…4 As a consequence, drug-resistant viruses can also be transmitted to other individuals, potentially fostering an increase of transmitted drug-resistant HIV to ART-naive patients. 5,6 V C The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.…”

Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

“…[5][6][7][8][9][10] In contrast and despite an expanded access to antiretroviral therapy in developing countries where non-B HIV subtypes predominate, pretherapy genotypic resistance testing is generally not available for clinical use. Reports have shown an increase in TDR prevalence in countries with expanding access to antiretroviral therapy, [11][12][13][14][15] though relatively little is known about the impact of non-subtype-B TDR on treatment outcomes specifically in resource-limited settings such as in sub-Saharan African countries, especially in rural communities. One study reports TDR prevalence in Kampala, the capital of Uganda, from 2009 to 2010 was 8.6%, but did not examine virologic response.…”