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Hepatitis B virus (HBV) and syphilis have been the most common co-infections that hinder treatment outcomes and increase early mortality among people living with human immunodeficiency virus (PLHIV). In this study, we aimed to determine the burden of HBV and syphilis co-infections and its impact on treatment outcomes among PLHIV in Ethiopia. We used data from the Ethiopian Population-based HIV Impact Assessment (EPHIA), which was a household-based national survey in 2017/2018. Human immunodeficiency virus (HIV) testing was done among 19,136 participants using the national testing algorithm and 662 participants (3.50%) were HIV positives who were further tested for viral hepatitis and syphilis co-infections using HBV surface antigen and Chembio DPP syphilis assay, respectively. Viral load, CD4 count and high-sensitivity C-reactive protein (hsCRP) were done to measure HIV treatment outcomes. Descriptive statistics were used to determine the burden of co-infections and a logistic regression model to evaluate the determinants of co-infections using STATA V17.0. Overall prevalence of HBV and syphilis co-infection was 5.5% and 2.2%, respectively. HBV and syphilis (double co-infection) was 5.9%. The highest prevalence of HBV co-infection was observed among 10–19 years age group (12.9%) and male participants (7.44%) while the highest syphilis co-infection was among people aged ≥50 years (3.5%) followed by age groups 40–49 (3.3%) and 10–19 years (3.2%). Syphilis co-infection was higher among males (5.2%) compared to females (1.1%). After adjusted regression analysis, HBV co-infected PLHIV had higher odds of virologic failure (AOR (95% confidence interval (CI)) = 6.3 (4.2–14.3)), immunosuppression (CD4 count < 500 cells/mm3) (AOR (95%CI) = 2.1(1.3–4.9)) and inflammation (hsCRP >10 mg/dL) (AOR (95%CI) = 9.2(4.3–14.6)). Immunosuppression was also significantly higher among syphilis co-infected PLHIV (AOR (95%CI) = 3.4 (1.3–5.2)). Burden of HBV and syphilis co-infections is high particularly among male and adolescent PLHIV and these co-infections hinder virologic and immunologic outcome in Ethiopia. Hence, the program shall enhance HBV and syphilis testing and treatment. [ABSTRACT FROM AUTHOR]

Background: High rates of disease progression and HIV drug resistance (HIVDR) among adults taking highly active antiretroviral treatment (HAART) in Sub-Saharan Africa were previously documented. However, children were generally not considered despite their greater risk. Hence, this study was aimed to evaluate HIV-1 disease progression and drug resistance mutation among children on first-line antiretroviral therapy in Ethiopia. Method: A longitudinal study was conducted among 551 HIV-positive children (<15 years old) recruited between 2017 and 2019 at 40 antiretroviral treatment delivery sites in Ethiopia. Disease progression was retrospectively measured over a 12-year (2007–2019) follow-up as the progress towards immunosuppression. Two consecutive viral load (VL) tests were conducted in 6-month intervals to assess virologic failure (VF). For children with VF, HIV-1 genotyping and sequencing was performed for the pol gene region using in-house assay validated at the Chinese Center for Disease Control and Prevention, and the Stanford HIVDB v9.0 algorithm was used for identification of drug resistance mutations. The Kaplan–Meier analysis and Cox proportional hazards regression model were used to estimate the rate and predictors of disease progression, respectively. Results: The disease progression rate was 6.3 per 100 person-years-observation (95% CI = 4.21–8.53). Overall immunosuppression (CD4 count < 200 cells/mm3) during the 12-year follow-up was 11.3% (95% CI = 7.5–15.1). Immunosuppression was significantly increased as of the mean duration of 10.5 (95% CI = 10.1–10.8) years (38.2%) to 67.8% at 12 years (p < 0.001). Overall, 14.5% had resistance to at least one drug, and 6.2% had multi-drug resistance. A resistance of 67.8% was observed among children with VF. Resistance to non-nucleotide reverse transcriptase inhibitors (NNRTI) and nucleotide reverse transcriptase inhibitors (NRTI) drugs were 11.4% and 10.1%, respectively. Mutations responsible for NRTI resistance were M184V (30.1%), K65R (12.1%), and D67N (5.6%). Moreover, NNRTI-associated mutations were K103N (14.8%), Y181C (11.8%), and G190A (7.7%). Children who had a history of opportunistic infection [AHR (95% CI) = 3.4 (1.8–6.2)], vitamin D < 20 ng/mL [AHR (95% CI) = 4.5 (2.1–9.9)], drug resistance [AHR (95% CI) = 2.2 (1.4–3.6)], and VF [AHR (95% CI) = 2.82 (1.21, 3.53)] had a higher hazard of disease progression; whereas, being orphan [AOR (95% CI) = 1.8 (1.2–3.1)], history of drug substitution [(AOR (95% CI) = 4.8 (2.1–6.5), hemoglobin < 12 mg/dL [AOR (95% CI) = 1.2 (1.1–2.1)] had higher odds of developing drug resistance. Conclusions: Immunosuppression was increasing over time and drug resistance was also substantially high. Enhancing routine monitoring of viral load and HIVDR and providing a vitamin-D supplement during clinical management could help improve the immunologic outcome. Limiting HAART substitution is also crucial for children taking HAART in Ethiopia. [ABSTRACT FROM AUTHOR]

Background. Studies have shown high early mortality after initiation of highly active antiretroviral therapy (HAART). We examined change in three-year survival and predictors of mortality of patients initiating HAART in Ethiopia since 2007 to 2019. Methods. A retrospective cohort study was conducted in 47 health facilities (HFs) using records of 11,013 adult patients initiating HAART from 2007 to 2019. Study subjects were stratified as four different cohorts based on their calendar year of HAART initiation: 2007-2010, 2011-2013, 2014-2016, and 2017-2019. HFs were selected using probability proportional to size of patients. Survival rate and predictors of mortality were estimated by the calendar year using the Kaplan-Meier and Cox proportional hazard, respectively. We generated a pooled estimate of survival rate and predicators of mortality. Results. Data from 1881, 3868, 3004, and 2260 patients were retrieved from each of the cohorts. Overall mortality for all cohorts at all times was 10.3%. A gradual decline of mortality was observed in the first three years of follow-up since 2007-2016 which were 21.37%, 10.03%, and 4.34% among patients who initiated HAART in 2007, 2011, and 2014 respectively. A mortality jump of 9.25% was observed among patents initiating HAART in 2017, which coincided with political instability happened in the country. Of the 21,638 person-years of follow-up among 11,013 adults, mortality was 5.23/100 person-years, while disaggregated by the cohorts, it was 14.77, 5.06, 2.12, and 4.17 per 100 person-years, respectively. Among all the cohorts, patients with CD4 count of ≤200 cells/mm3, unsuppressed viral load, poor adherence, and drug resistance in all cohorts, respectively, have overall 2.0 (95 % CI = 1.35 − 2.69), 4.66 (95 % CI = 2.53 − 6.72), 6.78 (95 % CI = 3.4 − 10.3), and 10.02 (95 % CI = 6.91 − 13.82) times of mortality risk than those without. Patients with bedridden for cohort initiating HAART during 2007 and 2011 were 2.0 (95 % CI = 1.35 − 2.69) times of mortality risk than those without. Conclusion. Patients initiating HAART from 2007 to 2016 have continuously improved their survival during three-year cohort follow-up in Ethiopia. The significant decline of survival among those who initiate HAART as of 2017 calls for program intervention. Low CD4 counts, unsuppressed viral load, poor adherence, and drug resistance could be used as predictors for increased mortality to monitor the quality of HAART and improve clinical management of HIV/AIDS patients. [ABSTRACT FROM AUTHOR]

Background: Treatment as prevention evolved into the universal HIV test-and-treat (UTT) strategy, which entails testing to the general population and treatment to every people living with HIV. We investigated universal testing (UT) performance and its determinants in urban Ethiopia and explore magnitude of late diagnosis and its impact on disease stages. Method: We used data from the Ethiopia Population Based HIV Impact assessment (EPHIA), conducted in 2017/2018 which was a cross-sectional and household-based study. For current analysis, we considered self-report first diagnosis to estimate universal testing irrespective of their serostatus and also consider HIV LAg avidity vs viral load vs plasma antiretroviral drug level algorithm to categorize the late diagnosis. We finally evaluate disease stages using CD4 count and viral load. A 2-level multilevel mixed-effect logistic regression model was employed. The effects of individual-level predictors were quantified by the estimates from the fixed-effect part of the model with p-value < 0.05. Result: Data were collected from 18,926 adults among those 29.4% of people living in Urban Ethiopia were never tested for HIV. Never tested females was 26.4% (95% CI = 25.3; 27.5). Never tested among divorced and widowed were 19.4% (95% CI: 17.3; 21.8) and 28.3% (95% CI: 24.6; 32.2), respectively. Never tested among elderly and youth were high (28.3% among 45–54 years old) to (41.2% among 55–64 years old) to 47.8% among 15–24 years old. Overall, late HIV diagnosis among adults in urban Ethiopia was 25.9% (95% CI: 21.7, 30.2). Late diagnosis varies by region ranged from 38.1% in the Gambella to 5.8% in Benishangul Gumuz. Advanced immune suppression (CD4 count < 350 cells/µl) among newly diagnosed long-term infection were significantly higher compared to those who were recently infected which accounted 47.8% (95%CI = 33.2–52.1) and 30.9% (95%CI = 21.3–32.2), respectively. Moreover, Viral load suppression were significantly lower among those who were late diagnosed 26.1% (95%CI = 13.6–33.8) compared to those of newly infected 89.6% (95%CI = 76.2; 93.4). Conclusion: With the aim of UT for high risk and priority population, the low rate of HIV testing among widowed, elderly, young adolescent and women in urban Ethiopia calls for enhanced HIV testing. Moreover, the low HIV testing and high late diagnosis among the high-burden regions calls for region-specific intervention. Advanced disease stages as a result of the high proportion of late diagnosis may impact on fueling community transmission and hinder treatment outcome among PLHIV. [ABSTRACT FROM AUTHOR]

Abbreviations: AIDS: acquired immune deficiency syndrome; CI: confidence interval; EPHI: Ethiopian Public Health Institute; HAART: highly active antiretroviral therapy; HIV: human immunodeficiency virus; HR: hazard ratio; Mg/dl: milligram per deciliter; TB: tuberculosis; PCP: pneumocystis carinii pneumonia; ZJU: Zhejiang University.

Objectives: The aim of this study was to evaluate HIV-1 drug resistance among patients failing first-line antiretroviral therapy in Ethiopia., Methods: A total of 699 adults infected with HIV (aged ≥15 years) who failed first-line Antiretroviral Therapy (ART) were recruited between 2017 and 2019 from 63 ART-providing sites in Ethiopia. Treatment failure was defined as patients with two consecutive viral loads (VLs) ≥1000 copies/mL within six months of follow-up. The pol gene region of HIV-1 was amplified and sequenced using an in-house assay of the Chinese Center for Disease Prevention and Control. The Stanford HIVDB v9.0 algorithm was used for identification of resistance mutations. Resistance mutations were characterized according to the 2019 International AIDS Society-USA mutation list. P values of <0.05 were considered statistically significant during multivariate analysis, which was done using SPSS v26.0 (SPSS Inc., Chicago, IL)., Results: Overall, HIV drug resistance (HIVDR) among patients failing first-line therapy in Ethiopia was 77.8%. Non-nucleoside/tide reverse transcriptase inhibitors (NNRTI) and NRTI resistance were 75.7% and 71.2%, respectively. Neverapine (NVP) and Efavirenz (EFV) accounted for 74.2% and 60.8% of HIVDR, respectively. About half (48.1%) of NRTI-associated mutations were responsible for Abacavir resistance, while 34% were responsible for multi-NRTI resistance. Mutations responsible for resistance to the commonly used EFV and NVP accounted for 62.9%, while resistance to Etravirine, Doravirine, and Rilivirine, which were not part of the country's ART program, were 37.1%, and can be explained by cross-resistance within the drug class. Protease Inhebitor(PI)associated resistance was detected in only 1.6% of the study's participants. The most common mutations identified were M184V (30.1%), K103N (18.7%), Y181C (13.6%), and K65R (12.1%). In a multivariate logistic regression analysis, predictors of HIVDR were prior ART exposure (adjusted odds ratio [AOR] = 2.3; 95% confidence interval [CI] = 1.8, 3.6), absence of HIV status disclosure (AOR=2.05; 95%CI=1.26, 3.35), CD4 count of ≤200 cells/mm 3 (AOR=1.94; 95%CI=1.21, 3.12), and bedridden status (AOR = 4.16; 95% CI = 3.21, 5.16)., Conclusion: The high-levels of HIVDR among patients with failure of first-line ART in Ethiopia calls for individualized HIVDR testing. Mutations associated with multi-NRTI and NNRTI cross-resistance may alert the program for considering drugs of higher genetic barrier targeting protease and other regions. Patients with low CD4 count and those who are bedridden should be given special attention for the potential development of HIVDR during clinical management., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)