Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999-2018

Abstract

HIV drug resistance (HIVDR) can become a public health concern, especially in low- and middle-income countries where genotypic testing for people initiating antiretroviral therapy (ART) is not available. For first-line regimens to remain effective, levels of transmitted drug resistance (TDR) need to be monitored over time. To determine the temporal trends of TDR in Mozambique, a search for studies in PubMed and sequences in GenBank was performed. Only studies covering the pol region that described HIVDR and genetic diversity from treatment naïve patients were included. A dataset from seven published studies and one novel unpublished study conducted between 1999 and 2018 were included. The Calibrated Population Resistance tool (CPR) and REGA HIV-1 Subtyping Tool version 3 for sequences pooled by sampling year were used to determine resistance mutations and subtypes, respectively. The prevalence of HIVDR amongst treatment-naïve individuals increased over time, reaching 14.4% in 2018. The increase was most prominent for non-nucleoside reverse transcriptase inhibitors (NNRTIs), reaching 12.7% in 2018. Subtype C was predominant in all regions, but a higher genetic variability (19% non-subtype C) was observed in the north region of Mozambique. These findings confirm a higher diversity of HIV in the north of the country and an increased prevalence of NNRTI resistance among treatment naïve individuals over time.

Keywords: HIV; Mozambique; drug; genetic diversity; molecular epidemiology; mutations; resistance; temporal trend; transmitted; treatment naïve.

Figure 1

The flow diagram scheme of the literature research used to construct the dataset: NGS; Next Generation Sequencing, pol-Polymerase. (Vubil et al., 2016 [21]).

Figure 2

Geographic distribution of HIV-1 subtypes within the regions of Mozambique. Pie charts showing subtype C and non-C HIV-1 isolates in the north (n = 142), central (n = 270), and south (n = 378) of Mozambique.

Figure 3

Temporal and regional trends for the overall, NNRTIs, NRTIs, and PIs having one or more major drug resistances over time in Mozambique. (A) Indicates the different temporal trends observed over the years. The x-axis represents the number of the HIV epidemic years since ARVs roll out, 2002–2004 (n = 167), 2007–2010 (n = 317), and 2018 (n = 118). (B) Indicates the different regions of the country. The x-axis represents the three different regions of Mozambique, south (n = 188), central (n = 273), and north (n = 141). The y-axis represents the prevalence rate of mutations calculated according to the Calibrated Population Resistance (CPR) analysis tool version 8.1. The p-value in each plot was established through the chi-square test over time.

Figure 4

HIV-1 drug resistance mutations identified in the 602 sequences used for the analysis for the various antiretroviral drug classes (A) NNRTI, (B) NRTI, and (C) PIs, * polymorphic mutations (accessory mutations) and ^ Thymidine Analog Mutations (TAMs).