Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients 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.

High Level of HIV Drug Resistance and Virologic Nonsuppression Among Female Sex Workers in Ethiopia: A Nationwide Cross-Sectional Study.

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.

HIV drug resistance early warning indicators in Ethiopia: Variability at regional and health facility levels and trend over time.

OBJECTIVE: The aim of this study was to assess status of early warning indicators (EWIs) for HIV drug resistance in Ethiopia. METHODS: A retrospective cohort study was conducted among 90 health facilities (HFs) in 2015. Data were abstracted for 'on time pill pickup' (EWI-I), 'Retention in care' (EWI-II), 'drug supply continuity'(EWI-III) and 'dispensing practices' (EWI-IV). Data analysis was conducted using WHO Excel tool and SPSS V20. RESULTS: EWI-IV was excellent across all of the six rounds of EWI surveys conducted between 2008 and 2015. There were improvements in EWI-II over time from 55.6% to 81%. However, EWI-I and EWI-III declined from 86.7% to 31% and 100% to 41%, respectively. During 2015, half of the HFs in Gambella, Amhara and Southern Nation, Nationalities and people regional (SNNPR) states achieved excellent performance for EWI-I. Similarly, all HFs in Afar, Amhara, Dire Dawa, Harari and Tigray regions achieved excellent performance for EWI-II. There were also differences by level of HFs for EWI-III; 62% of hospitals and 28% of health centers were out of stock of one or more ARV drugs by 2015. CONCLUSION: Excellent performance of EWI-IV and improvement of EWI-II over time shall be maintained. The program shall further work to ensure medication adherence and supply continuity.

Addis Ababa population-based pattern of cancer therapy, Ethiopia.

Cancer in Sub-Saharan Africa is becoming an important challenge for health services due to rising numbers of patients. In Addis Ababa with around 3.5 million inhabitants, more than 2000 cases are diagnosed annually. In this retrospective population-based cohort study we assessed completeness of and waiting time for cancer-therapy among patients registered in the Addis Ababa City Cancer Registry (AACCR), Ethiopia. Patient hospital files were retrieved to complete the data from AACCR. A total of 588 files were found (51% of those diagnosed from January to March 2012 and 2014). We analyzed completeness and waiting time of chemotherapy and radiotherapy; with completeness defined as ≥85% therapy received according to local guidelines. Analysis was done for the five most common cancer-types commonly treated with chemotherapy (breast, colorectal, non-Hodgkin`s lymphoma, lung and ovarian) and the four most common cancer-types commonly treated with radiotherapy (breast, cervical, head and neck and rectal). In our study, half of the patients (54.1%) received adequately dosed chemotherapy and 24.5% of patients received adequately dosed radiotherapy. The median waiting time was 2.1 months (Range: 0 to 20.72) for chemotherapy and 7 months (Range: 0.17 to 21.8) for radiotherapy. This study underscores the need for health system measures to improve cancer-directed therapy in Ethiopia, especially concerning radiotherapy.

HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013.

BACKGROUND: 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. METHODS: 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. RESULT: 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. CONCLUSION: 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.

Immunophenotyping of blood lymphocytes at birth, during childhood, and during adulthood in HIV-1-uninfected Ethiopians.

To obtain more insight into blood lymphocyte subpopulations of Ethiopians, we studied the immunologic profile of children and neonates and compared these data with those obtained from adults. Peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs) were collected from 137 HIV-1-uninfected subjects aged 0 (cord blood) up to 40 years. Lymphocyte subsets (T, B, and NK cells, CD4+ and CD8+ T cells) were determined and T cell activation (CD38 and HLA-DR) and differentiation (CD45RO and CD27) markers were measured on CD4+ and CD8+ T cells. The absolute number and percentage values of most lymphocyte subpopulations differed substantially with age. Neonates and children were found to have significantly higher CD4+ T cell counts compared to adults. The median absolute CD4 count at birth was comparable to those reported for Caucasians. At birth 97% of the CD4+ T cells were naîve and this proportion significantly declined to 14.2% during adulthood. In addition, activation of both CD4+ and CD8+ T cells, as determined by the double expression of HLA-DR and CD38, was observed in children under the age of 16 and adults, but not in neonates. A more differentiated phenotype (CD27-) was observed in adults compared to children for both CD4+ and CD8+ T cells. The immune alterations including the remarkably low CD4 count with highly depleted naîve phenotype and a persistently activated immune system seen in adult Ethiopians are not apparent at birth, but rather develop over time.