The 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. A 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. Four 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. TDR 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.

Objective: To determine viral load (VL) nonsuppression (VLN) rates, HIV drug resistance (HIVDR) prevalence, and associated factors among female sex workers (FSWs) in Ethiopia. Methods: A cross-sectional biobehavioral survey was conducted among FSWs in 11 cities in Ethiopia in 2014. Whole blood was collected, and HIVDR genotyping was performed. Logistic regression analysis was performed to identify factors associated with VLN and HIVDR. Results: Among 4900 participants, 1172 (23.9%) were HIV-positive and 1154 (98.5%) had a VL result. Participants were categorized into antiretroviral therapy (ART) (n = 239) and ART-naive (n = 915) groups based on self-report. From the 521 specimens (ART, 59; ART-naive, 462) with VL ≥1000 copies/mL, genotyping was successful for 420 (80.6%) and 92 (21.9%) had drug resistance mutations (DRMs). Pretreatment drug resistance (PDR) was detected in 16.5% (63/381) of the ART-naive participants. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTIs (NNRTIs), and dual-class DRMs were detected in 40 (10.5%), 55 (14.4%), and 35 (9.2%) of the participants, respectively. Among 239 participants on ART, 59 (24.7%) had VLN. Genotyping was successfully performed for 39 (66.1%). DRMs were detected in 29 (74.4%). All 29 had NNRTI, 23 (79.3%) had NRTI or dual-class DRMs. VLN was associated with age 35 years or older, CD4⁺ T-cell count <350 cells/mm³, and being forced into selling sex. PDR and acquired drug resistance were associated with CD4⁺ T-cell count <350 cells/mm³ (P < 0.001). Conclusions: The high VLN and HIVDR rates among FSWs underscore the need for targeted interventions to improve ART access and virologic monitoring to maximize the benefit of ART and limit the spread of HIV and HIVDR.

Background: The increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition. Methods: Participants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis. Results: Among 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis. Conclusions: Among adults receiving health center–based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.

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.

Background: Ethiopia is one of the sub-Saharan countries hit hard by the HIV epidemic. Previous studies have shown that subtype C dominates the Ethiopian HIV-1 epidemic, but the evolutionary and temporal dynamics of HIV-1 in Ethiopia have not been closely scrutinized. Understanding the evolutionary and epidemiological pattern of HIV is vital to monitor the spread, evaluate and implement HIV prevention strategies.Methods: We analyzed 1,276 Ethiopian HIV-1 subtype C polymerase (pol sequences), including 144 newly generated sequences, collected from different parts of the country from 1986 to 2017. We employed state-of-art maximum likelihood and Bayesian phylodynamic analyses to comprehensively describe the evolutionary dynamics of the HIV-1 epidemic in Ethiopia. We used Bayesian phylodynamic models to estimate the dynamics of the effective population size (N_e) and reproductive numbers (R_e) through time for the HIV epidemic in Ethiopia.Results: Our analysis revealed that the Ethiopian HIV-1 epidemic originated from two independent introductions at the beginning of the 1970s and 1980s from eastern and southern African countries, respectively, followed by epidemic growth reaching its maximum in the early 1990s. We identified three large clusters with a majority of Ethiopian sequences. Phylodynamic analyses revealed that all three clusters were characterized by high transmission rates during the early epidemic, followed by a decline in HIV-1 transmissions after 1990. R_e was high (4–6) during the earlier time of the epidemic but dropped significantly and remained low (R_e < 1) after the mid-1990. Similarly, with an expected shift in time, the effective population size (N_e) steadily increased until the beginning of 2000, followed by a decline and stabilization until recent years. The phylodynamic analyses corroborated the modeled UNAIDS incidence and prevalence estimates.Conclusion: The rapid decline in the HIV epidemic took place a decade before introducing antiretroviral therapy in Ethiopia and coincided with early behavioral, preventive, and awareness interventions implemented in the country. Our findings highlight the importance of behavioral interventions and antiretroviral therapy scale-up to halt and maintain HIV transmissions at low levels (R_e < 1). The phylodynamic analyses provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.