Pre-Treatment HIV Drug Resistance and Genetic Diversity in Cameroon: Implications for First-Line Regimens

Abstract

The efficacy of first-line antiretroviral therapy (ART) may be hampered by the presence of HIV drug resistance (HIVDR). We described HIV-1 pre-treatment drug resistance (PDR) patterns, effect of viral clades on PDR, and programmatic implications on first-line regimens in Cameroon. A sentinel surveillance of PDR was conducted from 2014 to 2019. Sequencing of HIV-1 protease and reverse transcriptase was performed, and HIVDR was interpreted using Stanford HIVdb.v.9.4. In total, 379 sequences were obtained from participants (62% female, mean age 36 ± 10 years). The overall PDR rate was 15.0% [95% CI: 11.8-19.0] nationwide, with significant disparity between regions (p = 0.03). NNRTI PDR was highest (12.4%), of which 7.9% had DRMs to EFV/NVP. Two regions had EFV/NVP PDR above the 10% critical threshold, namely the Far North (15%) and East (10.9%). Eighteen viral strains were identified, predominated by CRF02_AG (65.4%), with no influence of genetic diversity PDR occurrence. TDF-3TC-DTG predictive efficacy was superior (98.4%) to TDF-3TC-EFV (92%), p < 0.0001. The overall high rate of PDR in Cameroon, not substantially affected by the wide HIV-1 genetic diversity, underscores the poor efficacy of EFV/NVP-based first-line ART nationwide, with major implications in two regions of the country. This supports the need for a rapid transition to NNRTI-sparing regimens, with TDF-3TC-DTG having optimal efficacy at the programmatic level.

Keywords: Cameroon; HIV-1; first-line regimens; genetic diversity; pre-treatment drug resistance.

Figure 1

Phylogenetic Tree of HIV-1 sequences from ART-naive individuals. The evolutionary history was inferred by using the Maximum Likelihood method and Tamura-Nei model [1]. The tree with the highest log likelihood (−69,062.29) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the Tamura-Nei model and then selecting the topology with superior log. Cpx = complex recombinant forms.

Figure 2

Pre-treatment drug resistance (PDR) according to ARV class nationally and by geographical region. The histogram shows rates of PDR by ARV class, both at the national level and across regions. We note that overall PDR is high, with two regions (Far North and East) surpassing the 10% threshold for EFV/NVP.

Figure 3

Regional mapping of EFV/NVP-PDR.The figure shows the mapping of EFV/NVP PDR. Red colour denotes regions with high levels of PDR (above the 10% threshold), orange denotes regions with moderate levels of PDR (5–10%), and green denotes regions with levels of PDR below 5%.

Figure 4

Predictive efficacy of TLE (TDF + 3TC + EFV) vs. TLD (TDF + 3TC + DTG) in Cameroon. The figure shows predictive efficacy of TLD as compared to TLE. We observe superior predictive efficacy nationally and across all regions, with a marked superiority in the Far North region where EFV/NVP pre-treatment drug resistance was highest.