Circulating HIV-1 Integrase Genotypes in Tanzania: Implication on the Introduction of Integrase Inhibitors-Based Antiretroviral Therapy Regimen

Abstract

Tanzania has recently adapted World Health Organization antiretroviral guidelines that include integrase strand transfer inhibitors (INSTIs) in the first-line regimen. However, there is lack of evidence on integrase (IN) gene polymorphisms in viral strains circulating in Tanzania. In this study, we characterize IN gene polymorphisms in viral strains circulating in Dar es Salaam, Tanzania, before introduction of INSTIs. Plasma viral RNAs were prepared from 158 HIV-1-infected subjects, including 111 treated, but viremic (INSTI-naïve), subjects. A part of the pol gene encompassing the IN-coding region was amplified and directly sequenced by the Sanger sequencing method. Subtype analysis revealed that subtypes A1, C, and D and intersubtype recombinants were 42%, 38%, 11%, and 9%, respectively. Although multiple subtypes cocirculate, the IN gene exhibited a relatively conserved amino acid sequence pattern with an average Shannon entropy score of 0.16. No major INSTI resistance mutations were found; however, accessory resistance mutations at positions T97A, E157Q, G163E/K, and 128A/T were detected in 5% of subjects.

Primary resistance against integrase strand transfer inhibitors in integrase strand transfer inhibitor-naive patients failing first- and second-line ART in Tanzania

“…In synergy with other major mutations it reduces susceptibility to each of the INSTIs. 31 The occurrence of T97A in individuals with subtype A is similar to that in a study that reported the mutation as most prevalent in individuals with subtype A. 31 …”

“… 31 The occurrence of T97A in individuals with subtype A is similar to that in a study that reported the mutation as most prevalent in individuals with subtype A. 31 …”

“…T97A is a polymorphic INSTI-selected mutation that, depending on the subtype, occurs in about 1%–5% of viruses from untreated patients with the exception of subtype A (5%–10%), subtype J (33%) and group P (50%), and in our study it occurred in individuals infected with HIV-1 subtype A1. 31 This mutation alone has minimal effects on INSTI susceptibility. In synergy with other major mutations it reduces susceptibility to each of the INSTIs.…”

Interaction Analysis of Statistically Enriched Mutations Identified in Cameroon Recombinant Subtype CRF02_AG that can Influence the Development of Dolutegravir Drug Resistance Mutations

“…It is imperative to monitor the presence of mutations against INSTIs that can affect treatment outcomes. Furthermore, there is limited knowledge and data available for INSTI RAMs from studies that focuses on the SSA region, where over two-thirds of the current infected individuals reside (30,31). Our previous studies found low level of RAMSs against INSTIs (21).…”

HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania

“…Notably, increasing multi-class acquired drug resistance has been widely reported [ 10 , 11 , 22 , 23 ], as well as increasing NNRTI resistance amongst newly-diagnosed infants [ 24 ], showing the growing burden of drug resistance. Newer drugs in the class integrase strand transfer inhibitors (INSTI) such as dolutegravir have had very low to no drug resistance [ 25 ]. Nevertheless, suboptimal adherence and virologic monitoring with limited access to routine drug resistance mutation testing may increase the chances of their resistance.…”