BackgroundThe HIV-1 epidemic in Ethiopia has been shown to be dominated by two phylogenetically distinct subtype C clades, the Ethiopian (C’-ET) and East African (C-EA) clades, however, little is known about the temporal dynamics of the HIV epidemic with respect to subtypes and distinct clades. Moreover, there is only limited information concerning transmission of HIV-1 drug resistance (TDR) in the country.MethodsA cross-sectional survey was conducted among young antiretroviral therapy (ART)-naïve individuals recently diagnosed with HIV infection, in Gondar, Ethiopia, 2011–2013 using the WHO recommended threshold survey. A total of 84 study participants with a median age of 22 years were enrolled. HIV-1 genotyping was performed and investigated for drug resistance in 67 individuals. Phylogenetic analyses were performed on all available HIV sequences obtained from Gondar (n = 301) which were used to define subtype C clades, temporal trends and local transmission clusters. Dating of transmission clusters was performed using BEAST.ResultFour of 67 individuals (6.0%) carried a HIV drug resistance mutation strain, all associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). Strains of the C-EA clade were most prevalent as we found no evidence of temporal changes during this time period. However, strains of the C-SA clade, prevalent in Southern Africa, have been introduced in Ethiopia, and became more abundant during the study period. The oldest Gondar transmission clusters dated back to 1980 (C-EA), 1983 (C-SA) and 1990 (C’-ET) indicating the presence of strains of different subtype C clades at about the same time point in Gondar. Moreover, some of the larger clusters dated back to the 1980s but transmissions within clusters have been ongoing up till end of the study period. Besides being associated with more sequences and larger clusters, the C-EA clade sequences were also associated with clustering of HIVDR sequences. One cluster was associated with the G190A mutation and showed onward transmissions at high rate.ConclusionTDR was detected in 6.0% of the sequenced samples and confirmed pervious reports that the two subtype C clades, C-EA and C’-ET, are common in Ethiopia. Moreover, the findings indicated an increased diversity in the epidemic as well as differences in transmission clusters sizes of the different clades and association with resistance mutations. These findings provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.

Dolutegravir-based antiretroviral therapy (ART) has been scaled up in many developing countries, including Ethiopia. However, subtype-dependent polymorphic differences might influence the occurrence of HIV-drug-resistance mutations (HIVDRMs). We analyzed the prevalence of pre-treatment integrase strand transfer inhibitor (INSTI) HIVDRMs and naturally occurring polymorphisms (NOPs) of the integrase gene, using plasma samples collected as part of the national HIVDR survey in Ethiopia in 2017. We included a total of 460 HIV-1 integrase gene sequences from INSTI-naïve (n = 373 ART-naïve and n = 87 ART-experienced) patients. No dolutegravir-associated HIVDRMs were detected, regardless of previous exposure to ART. However, we found E92G in one ART-naïve patient specimen and accessory mutations in 20/460 (4.3%) of the specimens. Moreover, among the 288 integrase amino acid positions of the subtype C, 187/288 (64.9%) were conserved (<1.0% variability). Analysis of the genetic barrier showed that the Q148H/K/R dolutegravir resistance pathway was less selected in subtype C. Docking analysis of the dolutegravir showed that protease- and reverse-transcriptase-associated HIVDRMs did not affect the native structure of the HIV-1 integrase. Our results support the implementation of a wide scale-up of dolutegravir-based regimes. However, the detection of polymorphisms contributing to INSTI warrants the continuous surveillance of INSTI resistance.

Background: The use of surrogate markers for targeting viral load (VL) testing could be an alternative to universal VL testing during antiretroviral treatment (ART) and would allow for more effective resource allocation. We investigated the correlation between levels of HIV RNA and interferon-γ–inducible protein 10 (IP-10) in Ethiopian adults at 12 months after ART initiation. In addition, we specifically investigated differences in IP-10 levels between patients with and without virological suppression. Setting: Cohort of HIV-positive adults receiving ART at Ethiopian health centers. Methods: Using a nested case–control design, individuals without virological suppression (HIV RNA ≥ 150 copies/mL) at 12 months after ART initiation were gender-matched with virologically suppressed controls (1:2 ratio). IP-10 levels were correlated with HIV RNA, and the distribution of IP-10 was compared for 3 VL strata: <150 copies/mL (VL < 150), 150–999 copies/mL (VL150-999), and ≥1000 copies/mL (VL ≥ 1000). Results: At 12 months after ART initiation, the following VL distribution was found among 192 individuals (50% women): VL < 150, 122/192 (63.5%); VL150-999, 23/192 (12.0%); and VL ≥ 1000 47/192 (24.5%). IP-10 and HIV RNA levels were positively correlated (r = 0.481; P < 0.0001). Median IP-10 levels for the VL strata were VL < 150: 159 pg/mL [interquartile range (IQR) 121–246], VL150-999: 174 pg/mL (IQR 131–276), and VL ≥ 1000: 343 pg/mL (IQR 190–529), respectively. These differences were statistically significant for VL ≥ 1000 versus VL < 150 (adjusted P < 0.001) and VL150-999 (adjusted P = 0.004), respectively. Conclusions: IP-10 and HIV RNA levels during ART showed significant correlations, with significantly higher IP-10 concentration in ART recipients with VL ≥ 1000 copies/mL compared to those with suppressed or undetectable VL.