Risk Factors for Recent HIV Infections among Adults in 14 Countries in Africa Identified by Population-Based HIV Impact Assessment Surveys, 2015-2019.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Burden of HIV, HBV and syphilis among children in urban Ethiopia: Community-based cross-sectional study.

BACKGROUND: Children have largely been ignored in the fight against sexually transmitted infection (STI). Among children, STI is reported to be a globally emerging public health challenge. We evaluated the burden of HIV, hepatitis B virus (HBV) and syphilis among children (< 15 years old) and its determinants in urban Ethiopia. METHODS: For this study, we used data from the Ethiopian Population-based HIV Impact Assessment (EPHIA), collected through a nationally representative, community-based study conducted in Ethiopia from October 2017 to April 2018. We used plasma samples from 4729 children. Moreover, we linked the data and analysed them alongside their respective mothers. Child and maternal HIV status was determined using the national testing algorithm. Plasma samples from children were also tested for syphilis and HBV surface antigen. A descriptive analysis was done followed by bivariable analysis with 95% confidence interval (CI) at a significance level of p < 0.05. We finally evaluated predictors of STIs using regression analysis. RESULTS: HIV, HBV and syphilis prevalence rates among urban children in Ethiopia were 0.36%, 1.48% and 0.28%, respectively. Children living in Gambella and Addis Ababa had a 6.41-fold (95% CI: 3.20-9.88) and 4.20-fold (95% CI: 3.24-5.46) higher risk of HIV infection compared with those in Dire Dawa. Children of HIV-positive mothers had a 10.31-fold (95% CI: 3.20-18.19) higher risk of HIV infection, and if those mothers were not taking highly active antiretroviral therapy (HAART), the risk was 7.27 times higher (95% CI: 2.57-12.64). Those who were from HIV-positive mothers with viral load ≥ 1000 copies/mL had a 18.64-fold (95% CI: 6.36-31.24) higher risk of HIV infection and those with a history of breastfeeding had a 3.27-fold (95% CI: 1.11-5.67) higher risk. Children from Addis Ababa had a 3.26-fold (95% CI: 1.64-6.66) higher risk of HBV infection compared with those from Dire Dawa. Moreover, for those from HIV-positive mothers and whose mother was not taking HAART, the risk of HBV transmission was 6.37 (95% CI: 2.20-19.96) and 3.62 (95% CI: 1.27-11.29), respectively. Children living in Gambella, Somali, Afar and Tigray had a 7.21-fold (95% CI: 2.30-18.68), 3.10-fold (95% CI: 1.28-3.74) and 1.32-fold (95% CI: 1.11-3.38) higher risk of acquiring active syphilis compared with those living in Dire Dawa, respectively. Those from HIV-positive mothers also had a 4.22-fold (95% CI: 1.16-8.39) higher risk of acquiring active syphilis. CONCLUSION: The burden of HIV, HBV and syphilis was high among children in urban Ethiopia. The key determinants for the high burden of HIV, syphilis and HBV were maternal factors including maternal HIV status and breastfeeding. This might be due to the challenges associated with mother-to-child transmission. Hence, the programme shall focus on the elimination of the triple infections of HIV, syphilis and HBV.

Body and mind: retention in antiretroviral treatment care is improved by mental health training of care providers in Ethiopia.

BACKGROUND: Ethiopia has achieved a high coverage of antiretroviral treatment (ART), but maintaining lifelong care is still a great challenge. Mental illnesses often co-exist with HIV/AIDS and may compromise the retention on ART. In order to improve prolonged retention in ART care, basic training in mental health care was introduced for ART providers, but this hasn't been evaluated yet. The aim of this study was to examine if this training has improved patient retention in care. METHOD: A retrospective cohort study was employed to compare attrition from ART between clients attended by care provider trained with basic mental health service (exposed) and those in the standard ART follow-up care (unexposed) in public health facilities. A routine patient follow-up electronic database enrolled for ART between 2005 and 2017 was abstracted for the study. The Kaplan-Meier plot was used to compare the attrition rates between the two groups. The log-rank test was used to assess differences in the groups. The Cox proportional hazards regression model was used to determine predictors of attrition. We used estimated effect size of hazard ratios (HR) with 95% confidence intervals (CI). RESULT: During the 12 years of observation, 8009 study participants under ART were followed for 33,498 person-years. The incidence of attrition was 6.5 per 100 person-years and 21% higher in the unexposed group (HR 1.21; 95% CI 1.1, 1.3), and retention in care was significantly higher in the mental health exposed group throughout the study period. WHO clinical staging III/IV, tuberculosis coinfection, the male gender, and poor functional status were independent risk factors for attrition. CONCLUSION: We found that clients in the group exposed to mental health care training tended to have better retention in ART care with some variation according to gender, WHO Clinical stage and functional status. Training of ART providers in mental health may be considered in order to strengthen ART retention in low resource settings.

Human Immunodeficiency Virus Type-1 Genetic Diversity and Drugs Resistance Mutations among People Living with HIV in Karachi, Pakistan.

The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can contribute to ART failure and poor treatment outcomes. This study aimed to determine HIV-1 genetic diversity and identify drug-resistance mutations among people living with HIV in Karachi. A total of 364 HIV-positive individuals, with a median age of 36 years, were enrolled in the study. The HIV-1 partial pol gene was successfully sequenced from 268 individuals. The sequences were used to generate phylogenetic trees to determine clade diversity and also to assess the burden of DRMs. Based on the partial pol sequences, 13 distinct HIV-1 subtypes and recombinant forms were identified. Subtype A1 was the most common clade (40%), followed by CRF02_AG (33.2%). Acquired DRMs were found in 30.6% of the ART-experienced patients, of whom 70.7%, 20.7%, and 8.5% were associated with resistance to NNRTIs, NRTIs, and PIs, respectively. Transmitted DRMs were found in 5.6% of the ART-naïve patients, of whom 93% were associated with resistance against NNRTIs and 7% to PIs. The high prevalence of DRMs in ART-experienced patients poses significant challenges to the long-term benefits and sustainability of the ART program. This study emphasizes the importance of continuous HIV molecular epidemiology and drug resistance surveillance to support evidence-based HIV prevention, precise ART, and targeted AIDS care.

Identification of a novel first-generation HIV-1 circulating recombinant form (CRF152_DG) among people living with HIV in Karachi, Pakistan.

The objective of this study was to characterize a novel circulating recombinant form of human immunodeficiency virus type 1 (HIV-1) among people living with HIV in Karachi, Pakistan. We conducted near-full-length genome (NFLG) sequencing on eight samples exhibiting D/G recombination signals in the pol gene region. We successfully obtained NFLG sequences (790-9,614; with reference to the HXB2 genome) from four of the eight samples and then conducted phylogenetic and recombination analyses on them. The four NFLG sequences from our study and one DG unique recombinant form previously identified in the United Kingdom (GenBank accession: MF109700) formed a distinct monophyletic cluster with an Shimodaira-Hasegawa approximate likelihood ratio test node support value of 100%. Bootscan analyses of the five NFLG sequences of DG recombinants showed that all five NFLGs shared the same unique mosaic pattern of recombination breakpoints between D and G clades, with two D fragments in the pol and vif regions inserted into a G backbone. Subregion phylogenetic analyses confirmed these sequences to be a novel circulating recombinant form (CRF) composed of subtypes D and G. The DG recombinant sequences were eventually designated as CRF152_DG by the Los Alamos HIV Sequence Database staff. IMPORTANCE: In Pakistan, the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is becoming increasingly complex, compared to the early years of the epidemic that started after the detection of the first cases of HIV-1 in 1987 in Karachi. Based on the available molecular studies, two dominant HIV-1 clades, sub-subtype A1 and CRF02_AG, have been found to co-circulate with other clades, namely B, C, D, G, CRF01_AE, CRF35_A1D, and CRF56_cpx, in various urban areas of Pakistan. Several novel recombinant forms have also been detected. This first report of CRF152_DG highlights the complex nature of the HIV epidemic in Pakistan and emphasizes the importance of continual molecular surveillance (ideally based on whole-genome sequences) of HIV.

Prevalence of respiratory syncytial virus infection and associated factors in children aged under five years with severe acute respiratory illness and influenza-like illness in Ethiopia.

Objectives: Acute respiratory infections because of respiratory syncytial viruses (RSVs) are among the major leading causes of morbidity and mortality in children worldwide. RSV prevalence and its contributing factors among children aged under 5 years in Ethiopia are not well studied. To assess the prevalence and associated factors of RSV infection in children aged under 5 years using influenza sentinel surveillance sites in Ethiopia. Methods: A cross-sectional study design was used utilizing influenza-like illness/sever acute respiratory illness surveillance data from January 2021 to December 2022 at the Ethiopian Public Health Institute. Results: In total, 2234 cases were included, with an overall RSV positivity rate of 16.2%. The RSV positivity rate was high in children aged under 1 year (22.8%) and during fall season (24.8%). The RSV positivity rate was significantly associated with ages under 1 year (adjusted odds ratio [AOR] 2.8, 95% confidence interval [CI]: 1.89-4.15) and 1-2 years (AOR 1.9, 95% CI: 1.26-2.73) and the fall season (AOR 1.67, 95% CI: 1.17-2.38). Conclusion: The study revealed that a considerably high RSV positivity rate was detected in children aged under 5 years. The age of children and season have a significant association with RSV positivity rate. Further studies of RSV viral genotype, clinical characteristics, and disease outcome need to be conducted for a better understanding of the virus and disease outcome.

Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants-11 Sub-Saharan African Countries, 2015-2018.

BACKGROUND: HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018. METHOD: Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate. RESULTS: Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection. CONCLUSIONS: A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.

Impact TB co-infections on immune tolerance among people living with HIV: a systematic review.

BACKGROUND: The high-burden regions of Sub-Saharan Africa, which accounted for greater than 70% of the HIV epidemic, are disproportionately affected by the high rates of TB coinfection. This might be explained by, the low immune tolerance of the population due to malnutrition and chronic infections aggravating immune suppression. In this review, we discuss the immunopathogenesis of this common co-infection that causes significant morbidity and mortality in people living with HIV globally. METHODS: We used published studies using a two-step search strategy. Initial search of Pub Med Central and Google Scholar was undertaken followed by an analysis of the keywords. A second search using all the reference list of all identified reports and articles was searched for additional studies. Literature published as of January 1, 1981, that meets the inclusion criteria were considered. Qualitative data was extracted from papers included in the review. RESULT: Mortality occurs at both ends of the immunological spectrum of TB at one end HIV uninfected patient dies from asphyxiation from acute massive hemoptysis due to cavitary TB; at the other end, and far more frequently HIV-infected patient with disseminated TB dies from overwhelming infection with less evidence of focal pathology. There is no clear sign that the HIV-TB epidemic is slowing, especially considering the emergence of increasingly drug-resistant strains of MTB. A major challenge for the future is to discover immune correlates of TB protection and TB disease risk. Failure to define this conclusively has hindered TB prevention strategies, including the design of new TB vaccines to replace BCG, which provides only shortlived efficacy, prevents severe forms of the extra-pulmonary disease and is contraindicated in PLHIV. CONCLUSION: Understanding TB and HIV infection through immunological advances needs to be combined to describe the complex interactions between TB and HIV and the effects of ART. The complex interactions between the individual components of innate and acquired immune responses to TB and HIV infection is also likely to be the next step forward.

HIV-1 Disease Progression and Drug Resistance Mutations among Children on First-Line Antiretroviral Therapy in Ethiopia.

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.

Characterization of HIV-1 CRF02_AG/A3/G unique recombinant forms identified among children in Larkana, Pakistan.

Co-circulation of different human immunodeficiency virus type 1 HIV-1 subtypes among infected populations can lead to the generation of new recombinants. In Pakistan, subtype A1 and CRF02_AG are the dominant strains circulating among key populations. The high prevalence of new HIV infections among the key populations highlights the possibility of recombination between the dominant strains, which can lead to the generation of new recombinants. Here, we identified a recombinant cluster composed of CRF02_AG, sub-subtype A3, and subtype G among HIV-infected children in Larkana. For the study, 10 retrospectively collected samples, with recombination signals in the pol gene, were used to perform a near full-length genome NFLG sequencing. Of the 10 samples, NFLG was successfully sequenced from seven samples. Phylogenetic analysis of the seven NFLGs showed that all recombinants formed a distinct monophyletic cluster and were distinct from known HIV-1 circulating recombinant forms CRFs. Recombination analyses showed that all seven NFLGs shared a similar recombinant structure consisting of CRF02_AG, sub-subtype A3, and subtype G, with a sub-subtype A3 fragment inserted into pol and vif regions spanning from (HXB2: 4218-5518), and a subtype G fragment inserted into vpu, rev, tat and env regions spanning from (HXB2: 5957-8250) of the CRF02_AG backbone. The identification of unique recombinant forms may indicate the presence and transmission of several co-circulating lineages in Larkana, giving rise to newer CRFs. This study also highlights the importance of continuous molecular surveillance to fully understand HIV-1 genetic diversity in Pakistan, particularly in Larkana, which is the epicenter of HIV outbreaks.

The spectrum of opportunistic infections and malignancies among women on antiretroviral therapy in Ethiopia.

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.

Burden of hepatitis B virus and syphilis co-infections and its impact on HIV treatment outcome in Ethiopia: nationwide community-based study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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)). CONCLUSIONS: 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.

HAART induced inflammation, toxicity and its determinants among HIV positive children in Addis Ababa, Ethiopia.

Background: Highly Active Antiretroviral therapy (HAART) plays significant role in reduction of mortality among children infected with HIV. Despite the inevitable impact of HAART on inflammation and toxicity, there is limited evidence on its impact among children in Ethiopia. Moreover, evidence on contributing factors to toxicity has been poorly described. Hence, we evaluated HAART induced inflammation and toxicity among children taking HAART in Ethiopia. Method: This cross-sectional study was conducted among children (<15 years old) taking HAART in Ethiopia. Stored plasma samples and secondary data from a previous study on HIV-1 treatment failure were used for this analysis. By 2018, a total of 554 children were recruited from randomly selected 43 health facilities in Ethiopia. The different levels of liver (SGPT), renal (Creatinine) and hematologic toxicity (Hemoglobin) toxicity were assessed using established cut-off value. Inflammatory biomarkers (CRP and vitamin-D) were also determined. Laboratory tests were done at the national clinical chemistry laboratory. Clinical and baseline laboratory data were retrieved from the participant's medical record. Questionnaire was also administered to study guardians to assess individual factors to inflammation and toxicity. Descriptive statistics was used to summarize the characteristics of the study participants. Multivariable analysis was conducted and considered significant at P < 0.05. Result: Overall 363 (65.6%) and 199 (36%) of children taking HAART in Ethiopia developed some level of inflammation and vitamin-D in-sufficiency, respectively. A quarter of the children 140 (25.3%) were at Grade-4 liver toxicity while renal toxicity were 16 (2.9%). A third 275 (29.6%) of the children also developed anemia. Children who were on TDF+3 TC + EFV, those who were not virally suppressed and children with liver toxicity were at 17.84 (95%CI = 16.98, 18.82), 2.2 (95%CI = 1.67, 2.88) and 1.20 (95%CI = 1.14, 1.93) times risk of inflammation, respectively. Children on TDF+3 TC + EFV, those with CD4 count of <200 cells/mm3 and with renal toxicity were at 4.10 (95%CI = 1.64, 6.89), 2.16(95%CI = 1.31, 4.26) and 5.94 (95%CI = 1.18, 29.89) times risk of vitamin-D in-sufficiency, respectively. Predictors of liver toxicity were history of HAART substitution (AOR = 4.66; 95%CI = 1.84, 6.04) and being bedridden (AOR = 3.56; 95%CI = 2.01, 4.71). Children from HIV positive mother were at 4.07 (95%CI = 2.30, 6.09) times risk of renal toxicity while the different type of HAARTs had different level of risk for renal toxicity AZT+3 TC + EFV (AOR = 17.63; 95%CI = 18.25, 27.54); AZT+3 TC + NVP (AOR = 22.48; 95%CI = 13.93, 29.31); d4t+3 TC + EFV (AOR = 4.34; 95%CI = 2.51, 6.80) and d4t+3 TC + NVP (AOR = 18.91; 95%CI = 4.87, 27.74) compared to those who were on TDF+3 TC + NVP. Similarly, children who were on AZT+3 TC + EFV were at 4.92 (95%CI = 1.86, 12.70) times risk of anemia compared to those who were on TDF+ 3 TC + EFZ. Conclusion: The high level of HAART induced inflammation and liver toxicity among children calls for the program to consider safer regimens for pediatric patients. Moreover, the high proportion of vitamin-D in-sufficiency requires program level supplement. The impact of TDF+3 TC + EFV on inflammation and vitamin-D deficiency calls for the program to revise this regimen.

Predictors of HIV testing among youth 15-24 years in urban Ethiopia, 2017-2018 Ethiopia population-based HIV impact assessment.

INTRODUCTION: Youth (adolescents and young adults) aged 15-24 years comprise approximately 22% of Ethiopia's total population and make up 0.73% of HIV cases in urban Ethiopia. However, only 63% of HIV-positive youth are aware of their HIV status. We describe the HIV testing behaviors of youth 15-24 years and determined the characteristics of those who were most likely to be tested for HIV within the past year. METHODS: Using data from the 2017-2018 Ethiopia Population-based HIV Impact Assessment, we provide survey-weighted estimates and prevalence risk ratios for engagement in HIV testing in the 12 months preceding the survey. We model the likelihood of HIV testing one year or more before the survey compared to never testing, using a multinomial logistic regression model. RESULTS: Among HIV-negative and unaware HIV-positive youth 15-24 years old (N = 7,508), 21.8% [95% Confidence Interval (CI): 20.4-23.3%] reported testing for HIV in the last 12 months. Female youth [Prevalence Ratio (PR) = 1.6, 95% CI: 1.4-1.8], those aged 20-24 years (PR = 2.6, 95% CI:2.3-2.9), and those ever married (PR = 2.8, 95% CI: 2.5-3.1) were more likely to have tested for HIV within the last year. Adjusting for select demographic characteristics, sex with a non-spousal or non-live-in partner [Relative Risk (RR) = 0.3, 95% CI:0.1-0.8] among males did not increase their likelihood to test for HIV in the prior 12 months. Female youth engaged in antenatal care (RR = 3.0, 95% CI: 1.7-5.3) were more likely to test for HIV in the past year. CONCLUSION: The Ethiopian HIV case finding strategy may consider approaches for reaching untested youth, with a specific focus on adolescent males,15-19 years of age. This is critical towards achieving the UNAIDS HIV testing goal of 95% of all individuals living with HIV aware of their status by 2030.

Universal HIV testing and the impact of late diagnosis on disease stage among adults in urban Ethiopia.

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.

Evaluation of HIV-1 drug resistance among patients failing first-line antiretroviral therapy in Ethiopia.

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/mm3 (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.

HIV-1 genetic diversity a challenge for AIDS vaccine development: a retrospective bibliometric analysis.

BACKGROUND: Despite recent advances in human immunodeficiency virus-1 (HIV-1) prevention, a fast, safe, and effective vaccine will probably be necessary to end the HIV/AIDS pandemic. This study was conducted to evaluate global research trends and map the key bibliometric indices in HIV-1 genetic diversity from 1998 to 2021. METHODS: A comprehensive online search was conducted in the Web of Science Core Collection database to retrieve published literature on HIV-1 genetic diversity. Key bibliometric indicators were calculated and evaluated using HistCiteTM, Bibliometrix: An R-tool, and VOSviewer software for windows. RESULTS: A total of 2,060 documents written by 9,201 authors and published in 250 journals were included in the final analysis. Year 2012 was the most productive year with 121 (5.87%) publications. The most prolific author was Shao Yiming (n = 74, 3.59%) from Chinese Center for Disease Control and Prevention. The United States of America was the highly contributing and influential country (n = 681, 33.05%). AIDS Research and Human Retroviruses was the most productive journal (n = 562, 27.2%). Network visualization shows that HIV-1 was the most widely used author keyword. CONCLUSION: This study provides global research trends and detailed information on HIV-1 genetic diversity. The amount of scientific literature on HIV-1 genetic diversity research has rapidly increased in the last two decades. The maximum number of articles on HIV-1 genetic diversity was published in developed countries; therefore, a scientific research collaboration among researchers and institutes in low-income countries should be promoted and supported.

Survival and Predictors of Mortality among Adults Initiating Highly Active Antiretroviral Therapy in Ethiopia: A Retrospective Cohort Study (2007-2019).

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.

Spatial distribution and determinants of HIV prevalence among adults in urban Ethiopia: Findings from the Ethiopia Population-based HIV Impact Assessment Survey (2017-2018).

The design and evaluation of national HIV programs often rely on aggregated national data, which may obscure localized HIV epidemics. In Ethiopia, even though the national adult HIV prevalence has decreased, little information is available about local areas and subpopulations. To inform HIV prevention efforts for specific populations, we identified geographic locations and drivers of HIV transmission. We used data from adults aged 15-64 years who participated in the Ethiopian Population-based HIV Impact Assessment survey (October 2017-April 2018). Location-related information for the survey clusters was obtained from the 2007 Ethiopia population census. Spatial autocorrelation of HIV prevalence data were analyzed via a Global Moran's I test. Geographically weighted regression analysis was used to show the relationship of covariates. The finding indicated that uncircumcised men in certain hotspot towns and divorced or widowed individuals in hotspot woredas/towns might have contributed to the average increase in HIV prevalence in the hotspot areas. Hotspot analysis findings indicated that, localized, context-specific intervention efforts tailored to at-risk populations, such as divorced or widowed women or uncircumcised men, could decrease HIV transmission and prevalence in urban Ethiopia.

Progress towards the UNAIDS 90-90-90 targets among persons aged 50 and older living with HIV in 13 African countries.

INTRODUCTION: Achieving optimal HIV outcomes, as measured by global 90-90-90 targets, that is awareness of HIV-positive status, receipt of antiretroviral (ARV) therapy among aware and viral load (VL) suppression among those on ARVs, respectively, is critical. However, few data from sub-Saharan Africa (SSA) are available on older people (50+) living with HIV (OPLWH). We examined 90-90-90 progress by age, 15-49 (as a comparison) and 50+ years, with further analyses among 50+ (55-59, 60-64, 65+ vs. 50-54), in 13 countries (Cameroon, Cote d'Ivoire, Eswatini, Ethiopia, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe). METHODS: Using data from nationally representative Population-based HIV Impact Assessments, conducted between 2015and 2019, participants from randomly selected households provided demographic and clinical information and whole blood specimens for HIV serology, VL and ARV testing. Survey weighted outcomes were estimated for 90-90-90 targets. Country-specific Poisson regression models examined 90-90-90 variation among OPLWH age strata. RESULTS: Analyses included 24,826 HIV-positive individuals (15-49 years: 20,170; 50+ years: 4656). The first, second and third 90 outcomes were achieved in 1, 10 and 5 countries, respectively, by those aged 15-49, while OPLWH achieved outcomes in 3, 13 and 12 countries, respectively. Among those aged 15-49, women were more likely to achieve 90-90-90 targets than men; however, among OPLWH, men were more likely to achieve first and third 90 targets than women, with second 90 achievement being equivalent. Country-specific 90-90-90 regression models among OPLWH demonstrated minimal variation by age stratum across 13 countries. Among OLPWH, no first 90 target differences were noted by age strata; three countries varied in the second 90 by older age strata but not in a consistent direction; one country showed higher achievement of the third 90 in an older age stratum. CONCLUSIONS: While OPLWH in these 13 countries were slightly more likely than younger people to be aware of their HIV-positive status (first 90), this target was not achieved in most countries. However, OPLWH achieved treatment (second 90) and VL suppression (third 90) targets in more countries than PLWH <50. Findings support expanded HIV testing, prevention and treatment services to meet ongoing OPLWH health needs in SSA.