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.

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.

Rates of confirmatory HIV testing, linkage to HIV services, and rapid initiation of antiretroviral treatment among newly diagnosed children living with HIV in Ethiopia: perspectives from caregivers and healthcare workers.

BACKGROUND: Successful linkage to HIV services and initiation of antiretroviral treatment (ART) for children living with HIV (CLHIV) is critical to improve pediatric ART coverage. We aimed to assess confirmatory testing, linkage, and rapid ART initiation among newly diagnosed CLHIV in Ethiopia from the perspectives of caregivers and healthcare workers (HCWs). METHODS: We conducted standardized surveys with HCWs and caregivers of children 2-14 years who were diagnosed with HIV but not yet on ART who had been identified during a cross-sectional study in Ethiopia from May 2017-March 2018. Eight health facilities based on their HIV caseload and testing volume and 21 extension sites were included. Forty-one children, 34 care givers and 40 healthcare workers were included in this study. Three months after study enrollment, caregivers were surveyed about timing and experiences with HIV service enrollment, confirmatory testing, and ART initiation. Data collected from HCWs included perceptions of confirmatory testing in CLHIV before ART initiation. SPSS was used to conduct descriptive statistics. RESULTS: The majority of the 41 CLHIV were enrolled to HIV services (n = 34, 83%) and initiated ART by three months (n = 32, 94%). Median time from diagnosis to ART initiation was 12 days (interquartile range 5-18). Five children died before the follow-up interview. Confirmatory HIV testing was conducted in 34 children and found no discordant results; the majority (n = 23, 68%) received it within one week of HIV diagnosis. Almost all HCWs (n = 39/40, 98%) and caregivers (n = 31/34, 91%) felt better/the same about test results after conducting confirmatory testing. CONCLUSION: Opportunities remain to strengthen linkage for newly diagnosed CLHIV in Ethiopia through intensifying early follow-up to ensure prompt confirmatory testing and rapid ART initiation. Additional services could help caregivers with decision-making around treatment initiation for their children.

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.

Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient.

A comprehensive assessment of immunological profiles during HIV-TB co-infection is essential to predict mortality, and facilitate the development of effective diagnostic assays, therapeutic agents, and vaccines. Expression levels of 105 immune-related genes were measured at enrolment and 6th month follow-up from 9 deceased HIV and TB coinfected patients who died between 3 and 7th months follow-up and at enrolment, 6th and 18th month from 18 survived matched controls groups for 2 years. Focused gene expression profiling was assessed from peripheral whole blood using a dual-color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification assay. Eleven of the 105 selected genes were differentially expressed between deceased individuals and survivor-matched controls at baseline. At baseline, IL4δ2 was significantly more highly expressed in the deceased group than survivor matched controls, whereas CD3E, IL7R, PTPRCv1, CCL4, GNLY, BCL2, CCL5, NOD1, TLR3, and NLRP13 had significantly lower expression levels in the deceased group compared to survivor matched controls. At baseline, a non-parametric receiver operator characteristic curve was conducted to determine the prediction of mortality of single genes identified CCL5, PTPRCv1, CD3E, and IL7R with Area under the Curve of 0.86, 0.86, 0.86, and 0.85 respectively. The expression of these genes in the survived control was increased at the end of TB treatment from that at baseline, while decreased in the deceased group. The expression of PTPRCv1, CD3E, CCL5, and IL7R host genes in peripheral blood of patients with TB-HIV coinfected can potentially be used as a predictor of mortality in the Ethiopian setting. Anti-TB treatment might be less likely to restore gene expression in the level expression of the deceased group. Therefore, other new therapeutics that can restore these genes (PTPRCv1, CD3E, IL7R, and CCL5) in the deceased groups at baseline might be needed to save lives.

Adapting strategies for effective and efficient pediatric HIV case finding in low prevalence countries: risk screening tool for testing children presenting at high-risk entry points in Ethiopia.

BACKGROUND: Implementing effective and efficient case-finding strategies is crucial to increasing pediatric antiretroviral therapy coverage. In Ethiopia, universal HIV testing is conducted for children presenting at high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC); however, low positivity rates observed at inpatient, malnutrition and OVC entry points warrant re-assessing current case-finding strategies. The aim of this study is to develop HIV risk screening tool applicable for testing children presenting at inpatient, malnutrition and OVC entry points in low-HIV prevalence settings. METHODS: The study was conducted from May 2017-March 2018 at 29 public health facilities in Amhara and Addis Ababa regions of Ethiopia. All children 2-14 years presenting to five high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC) were enrolled after consent. Data were collected from registers, medical records, and caregiver interviews. Screening tools were constructed using predictors of HIV positivity as screening items by applying both logistic regression and an unweighted method. Sensitivity, specificity and number needed to test (NNT) to identify one new child living with HIV (CLHIV) were estimated for each tool. RESULTS: The screening tools had similar sensitivity of 95%. However, the specificities of tools produced by logistic regression methods (61.4 and 65.6%) which are practically applicable were higher than those achieved by the unweighted method (53.6). Applying these tools could result in 58‒63% reduction in the NNT compared to universal testing approach while maintaining the overall number of CLHIV identified. CONCLUSION: The screening tools developed using logistic regression method could significantly improve HIV testing efficiency among children presenting to malnutrition, inpatient, and OVC entry points in Ethiopia while maintaining case identification. These tools are simplified to practically implement and can potentially be validated for use at various entry points. HIV programs in low-prevalence countries can also further investigate and optimize these tools in their settings.

Finding Children Living With HIV in Low-prevalence Countries: HIV Prevalence and Testing Yield From 5 Entry Points in Ethiopia.

BACKGROUND: Limited data in low HIV prevalence settings such as Ethiopia limit policy development and implementation of optimized pediatric testing approaches to close the treatment gap. This study aimed to determine HIV prevalence, testing yield and factors associated with HIV among children at 5 entry points. METHODS: We conducted a cross-sectional study from May 2017 to March 2018 in 29 public health facilities in Amhara and Addis Ababa regions in Ethiopia. Children 2-14 years were enrolled through 5 entry points. Data were obtained from registers, medical records and interviews with caregivers. HIV prevalence and testing yields were calculated for each entry point. Mixed-effects logistic regression analysis identified factors associated with undiagnosed HIV. RESULTS: The study enrolled 2166 children, of whom 94 were HIV positive (40 newly diagnosed). HIV prevalence and testing yield were the highest among children of HIV-positive adults (index testing; 8.2% and 8.2%, respectively) and children presenting to tuberculosis clinics (7.9% and 1.8%) or with severe malnutrition (6.5% and 1.4%). Factors associated with undiagnosed HIV included tuberculosis or index entry point [adjusted odds ratio (aOR), 11.97; 95% CI 5.06-28.36], deceased mother (aOR 4.55; 95% CI 1.30-15.92), recurrent skin problems (aOR 17.71; 95% CI 7.75-40.43), severe malnutrition (aOR 4.56; 95% CI 2.04-10.19) and urban residence (aOR 3.47; 95% CI 1.03-11.66). CONCLUSIONS: Index testing is a critical strategy for pediatric case finding in Ethiopia. Strategies and resources can prioritize minimizing missed opportunities in implementing universal testing for very sick children (tuberculosis, severe malnutrition) and implementing targeted testing in other entry points through use of factors associated with HIV.

Serum level of high sensitive C-reactive protein and IL - 6 markers in patients with treatment-resistant schizophrenia in Ethiopia: a comparative study.

BACKGROUND: Accumulating evidence indicates that schizophrenia is accompanied by significant activation of the immune system; however, there is limited data from low and middle-income countries (LMIC). Inflammatory markers may be more relevant in LMIC settings where infectious conditions are more prevalent and may thus play some role in the causation and maintenance of schizophrenia. The aim of this study was to assess the level of inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with schizophrenia. MATERIALS AND METHODS: The study population consisted of a total of 132 study participants; 82 participants with schizophrenia and 50 controls. hsCRP and IL-6 were measured using Cobas Integra 400 Plus and Cobas e 411 analysers respectively. RESULTS: The levels of hsCRP and IL-6 were significantly increased among participants with schizophrenia compared to controls: hsCRP mean value 2.87 ± 5.6 vs 0.67 ± 0.6 mg/L; IL-6 mean value 6.63 ± 5.6 vs 3.37 ± 4.0 pg/ml. Controlling for potential confounders (age, sex and body mass index), having a diagnosis of schizophrenia remained significantly associated with increased hsCRP and IL-6. CONCLUSION: The results confirm that inflammatory processes may have a role in the pathophysiology of schizophrenia regardless of setting. Despite failure of some interventions with anti-inflammatory properties, interventions to reduce inflammation are still worth pursuing.

Incidence of Hepatotoxicity and Factors Associated During Highly Active Antiretroviral Therapy in People Living with HIV in Ethiopia: A Prospective Cohort Study.

INTRODUCTION: Hepatotoxicity is one of the risk factors associated with treatment non-adherence, which is the main risk factor for drug resistance. Therefore, this study aimed to determine the incidence and risk factors of hepatotoxicity during highly active antiretroviral therapy (HAART) among people living with HIV in Ethiopia. METHODS: A prospective cohort study was conducted between April 2007 and January 2011 at Saint Peter Specialized Hospital, Akaki and Kality Health Centers, Addis Ababa, Ethiopia. A total of 316 HIV-infected adult individuals (70 participants were HIV and TB co-infected and 246 were infected with HIV alone) were included in this study. The study participants were followed for a total of 18 months with or without HAART. Socio-demographic data were collected using a structured questionnaire, and venous blood samples were collected for laboratory tests. Logistic regression and Poisson regression were used to determine the independent effect of each variable on hepatotoxicity at baseline and end of follow-up. RESULTS: Of 316 HIV-infected people, 72 (22.8%) participants had an elevated ALT/AST which was 100% mild-to moderate hepatotoxicity at baseline. Baseline CD4 T-cell count (p = 0.027) and HIV co-infection with TB (p < 0.001) were independently associated with hepatotoxicity at baseline. The overall incidence rate of hepatotoxicity in participants on HAART (21.8 per 100 person-years) was lower than participants who were HAART naïve (33.3 per 100 person-years) (p = 0.009). CONCLUSION: High incidence of mild-to-moderate hepatotoxicity and low severe hepatotoxicity were observed in HIV-infected individuals who were on HAART or were HAART naïve. HAART may minimize the occurrence of hepatotoxicity. Although HAART could minimize hepatotoxicity among HIV-infected people, to manage mild and moderate hepatotoxicity liver function test monitoring is required.

Validation and Optimization of Host Immunological Bio-Signatures for a Point-of-Care Test for TB Disease.

The development of a non-sputum-based, point-of-care diagnostic test for tuberculosis (TB) is a priority in the global effort to combat this disease, particularly in resource-constrained settings. Previous studies have identified host biomarker signatures which showed potential, but there is a need to validate and refine these for development as a test. We recruited 1,403 adults presenting with symptoms suggestive of pulmonary TB at primary healthcare clinics in six countries from West, East and Southern Africa. Of the study cohort, 326 were diagnosed with TB and 787 with other respiratory diseases, from whom we randomly selected 1005 participants. Using Luminex® technology, we measured the levels of 20 host biomarkers in serum samples which we used to evaluate the diagnostic accuracy of previously identified and novel bio-signatures. Our previously identified seven-marker bio-signature did not perform well (sensitivity: 89%, specificity: 60%). We also identified an optimal, two-marker bio-signature with a sensitivity of 94% and specificity of 69% in patients with no history of previous TB. This signature performed slightly better than C-reactive protein (CRP) alone. The cut-off value for a positive diagnosis differed for human immuno-deficiency virus (HIV)-positive and -negative individuals. Notably, we also found that no signature was able to diagnose TB adequately in patients with a prior history of the disease. We have identified a two-marker, pan-African bio-signature which is more robust than CRP alone and meets the World Health Organization (WHO) target product profile requirements for a triage test in both HIV-negative and HIV-positive individuals. This signature could be incorporated into a point-of-care device, greatly reducing the necessity for expensive confirmatory diagnostics and potentially reducing the number of cases currently lost to follow-up. It might also potentially be useful with individuals unable to provide sputum or with paucibacillary disease. We suggest that the performance of TB diagnostic signatures can be improved by incorporating the HIV-status of the patient. We further suggest that only patients who have never had TB be subjected to a triage test and that those with a history of previous TB be evaluated using more direct diagnostic techniques.

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.

Gene expression profiles classifying clinical stages of tuberculosis and monitoring treatment responses in Ethiopian HIV-negative and HIV-positive cohorts.

BACKGROUND: Validation of previously identified candidate biomarkers and identification of additional candidate gene expression profiles to facilitate diagnosis of tuberculosis (TB) disease and monitoring treatment responses in the Ethiopian context is vital for improving TB control in the future. METHODS: Expression levels of 105 immune-related genes were determined in the blood of 80 HIV-negative study participants composed of 40 active TB cases, 20 latent TB infected individuals with positive tuberculin skin test (TST+), and 20 healthy controls with no Mycobacterium tuberculosis (Mtb) infection (TST-), using focused gene expression profiling by dual-color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification assay. Gene expression levels were also measured six months after anti-TB treatment (ATT) and follow-up in 38 TB patients. RESULTS: The expression of 15 host genes in TB patients could accurately discriminate between TB cases versus both TST+ and TST- controls at baseline and thus holds promise as biomarker signature to classify active TB disease versus latent TB infection in an Ethiopian setting. Interestingly, the expression levels of most genes that markedly discriminated between TB cases versus TST+ or TST- controls did not normalize following completion of ATT therapy at 6 months (except for PTPRCv1, FCGR1A, GZMB, CASP8 and GNLY) but had only fully normalized at the 18 months follow-up time point. Of note, network analysis comparing TB-associated host genes identified in the current HIV-negative TB cohort to TB-associated genes identified in our previously published Ethiopian HIV-positive TB cohort, revealed an over-representation of pattern recognition receptors including TLR2 and TLR4 in the HIV-positive cohort which was not seen in the HIV-negative cohort. Moreover, using ROC cutoff ≥ 0.80, FCGR1A was the only marker with classifying potential between TB infection and TB disease regardless of HIV status. CONCLUSIONS: Our data indicate that complex gene expression signatures are required to measure blood transcriptomic responses during and after successful ATT to fully diagnose TB disease and characterise drug-induced relapse-free cure, combining genes which resolve completely during the 6-months treatment phase of therapy with genes that only fully return to normal levels during the post-treatment resolution phase.

The serum concentration of vitamin B12 as a biomarker of therapeutic response in tuberculosis patients with and without human immunodeficiency virus (HIV) infection.

BACKGROUND: Prior to clinical trials of new tuberculosis (TB) drugs or therapeutic vaccines, it is necessary to develop monitoring tools to predict treatment outcomes in TB patients. METHODS: Micronutrients concentration level was determined from a total of 262 study participants with five clinical groups: 57 TB patients coinfected with HIV (HIV+TB+), 87 active TB Patients (TB cases), 71 HIV infected without active and latent TB infection (HIV+TST-), 22 latent TB infection (TST+) and 25 healthy controls (TST-). Vitamin A concentration was measured using high-performance liquid chromatography (HPLC), whereas iron and vitamin B12 concentrations were measured using Cobas® 6000 analyzer. RESULT: The serum concentration levels of iron, vitamin A and vitamin B12 had a significant difference between active TB and latent (LTBI) or healthy controls. Six months after treatment, the serum concentration levels of vitamin A, vitamin B12 and iron in tuberculosis became indistinguishable from the levels of LTBIs and healthy control individuals. The concentration levels of iron and vitamin B12 in HIV+TB+patients at the end of TB treatment were normalized to the levels observed in healthy controls (TST-) regardless of HAART treatment. However, the concentration level of vitamin A in HIV+TB+patients HAART untreated at the end of TB treatment was not normalized to the levels observed in healthy controls (TST-) or HAART untreated HIV+TST-. CONCLUSION: Detecting serum concentration levels of vitamin B12 and vitamin A might be used as a biomarker of the diagnostic method of active TB regardless of HIV-infected individuals. Moreover, detecting serum concentration of vitamin B12 might also be used for TB treatment responses monitoring biomarker in TB-HIV-co-infected individuals regardless of HAART (in)eligibility and therapy.

Prevalence of sexually transmitted infections (HIV, hepatitis B virus, herpes simplex virus type 2, and syphilis) in pregnant women in Ethiopia: Trends over 10 years (2005-2014).

OBJECTIVES: This study was performed to determine the trends in seroprevalence of four major sexually transmitted infections (STIs) (HIV, hepatitis B virus (HBV), herpes simplex virus type 2 (HSV-2), and syphilis) over a 10-year period (2005-2014) in pregnant women in Ethiopia. METHODS: Pregnant women (15-49 years old) who were enrolled in the antenatal care-based national HIV surveillance were included. Serological tests for HIV, HBV, HSV-2, and syphilis were done on serum/plasma samples. RESULTS: A total of 4887 pregnant women were included. Results showed a decline in prevalence of these STIs by 40-60% over the 10 years (2005-2014): HIV (10.5% to 5.5%), syphilis (2.5% to 1.1%), HBV (12.6% to 6.7%), and HSV-2 (47.5% to 28.5%). In 2014, 109/4887 (2.2%) women had triple infections. In 2005, 2007, and 2009, the prevalence of HSV-2 in the older age group (35-45 years) (47.1%, 47.4%, and 50.0%, respectively) was higher than that in the younger age group (15-24 years) (40.9%, 19.5%, and 20.2%, respectively). Age category (Chi-square=22.4, p<0.001), study sites/residence (Chi-square=135.2, p=0.001), and time/years (Chi-square=58.9, p=0.001) were associated with a positive HSV-2 test result. CONCLUSIONS: A decline in HIV, HBV, HSV-2, and syphilis of >40% was seen over the years in Ethiopia. However, an intermediate endemicity level of HBV and higher prevalence of HIV and HSV-2 by 2014, suggest the need to strengthen prevention strategy for STIs.

Prevalence of HIV and other infections and injection behaviours among people who inject drugs in Addis Ababa, Ethiopia.

BACKGROUND: Ethiopia is one of the sub-Saharan African countries most affected by HIV/AIDS. However, the country lacks data describing the extent of the epidemic among people who inject drugs (PWID). Thus, a bio-behavioural study was conducted in 2015 to generate strategic information on the magnitude of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis and related risk behaviours among PWID in Addis Ababa. METHODS: A cross-sectional study using respondent-driven sampling was conducted among people reported to have injected illicit drugs within 6 months before the study. Males and females aged 15 years or above and who were resident in Addis Ababa were included in the study between 26 March and 22 May 2015. Data was analysed using respondent-driven (RDS) Analyst software. RESULTS: A total of 237 participants, including 6 seeds, enrolled in the study; most of the PWID were males (96%) with a mean age of 26 years. Most (79%) of the PWID reported injecting heroin but also reported using non-injecting drugs, including marijuana or ganja (47%) and/or khat (31%). Forty per cent of PWID reported ever sharing needles and 56% reported sharing other injecting equipment. However, only 14% reported injecting daily, and 49% reported injecting only 1 to 3 times a month. HIV prevalence was 6%, HBV was 5.1%, HCV was 2.9% and syphilis 5.1% among PWID. Among HIV-positive PWID, 60% reported sharing a needle the last time they injected. CONCLUSION: Even though the prevalence of HIV among drug users is not much higher than in the general population in Addis Ababa, the needle sharing prevalence was high. Thus, this baseline study shows the need to establish harm reduction programmes and prevention strategies for the PWID in Addis Ababa.

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.

Associations of gender and serum total cholesterol with CD4+ T cell count and HIV RNA load in antiretroviral-naïve individuals in Addis Ababa.

BACKGROUND: Males are more susceptible than females to infections due to the differences in endocrine-immune interactions. Furthermore, it is reported that lowering cell cholesterol impairs viral replication and infection in vitro. However, the production of oxysterols in vivo by oxidation of cholesterol may result in inhibition of HIV replication. Therefore, this study was designed to determine the associations of gender and serum total cholesterol with CD4+ T cell counts and/or WHO clinical stages, and HIV ribonucleic acid (RNA) load in antiretroviral therapy (ART) naive study population with known sero-positive time of stay in Addis Ababa.  METHODS: A cross-sectional study was conducted from February to August 2013 on 594 HIV-1 infected ART-naïve adult study participants in four hospitals Addis Ababa. CD4+ T-cell count, HIV RNA load, hemoglobin and fasting serum total cholesterol were determined. Socio-demographic characteristics, WHO clinical stages, and height and weight were collected from patients' chart and triangulated by structured questionnaire. Pearson chi-square test, Spearman rank correlation and univariate and multivariate linear/logistic regression analyses were carried out to determine associations. RESULTS: Mean HIV RNA load was found to be lower in women than in men (p < 0.05). CD4+ T cell count and serum total cholesterol were found to be significantly correlated with HIV RNA load (p < 0.01). Women were at lower risk of having higher HIV RNA load in comparison to men. In addition, having lower concentrations of serum total cholesterol was found to be independent predictor of higher HIV RNA load in comparison to those with higher concentrations of cholesterol in serum (p < 0.05). The multivariate binomial logistic regression also showed that the immune status was better in women than men, and in the presence of higher serum total cholesterol (p < 0.05). CONCLUSION: Gender and serum total cholesterol were found to be associated and independent predictors of HIV RNA load, and CD4+ cell count and/or WHO clinical stages. There is a significant lower HIV RNA load and better CD4+ T cell count in women and those study participants with higher serum total cholesterol.

Host Gene Expression Kinetics During Treatment of Tuberculosis in HIV-Coinfected Individuals Is Independent of Highly Active Antiretroviral Therapy.

Background: Limitations in diagnostic tools to discriminate between active tuberculosis and latent Mycobacterium tuberculosis infection and for monitoring antituberculosis treatment responses are major challenges in tuberculosis control, especially in human immunodeficiency virus (HIV)-coinfected individuals. Methods: Expression levels of 105 immune-related genes were determined in 131 HIV-infected patients with active tuberculosis (n = 48), patients with latent M. tuberculosis infection (LTBI; n = 37), and controls with no M. tuberculosis infection (n = 46) in Addis Ababa, Ethiopia, using focused gene expression profiling with a dual-color reverse-transcription multiplex ligation-dependent probe amplification assay. Results: Within the cohort of HIV-positive subjects, the expression profiles of 7 genes at baseline (FCGR1A, RAB24, TLR1, TLR4, MMP9, NLRC4, and IL1B) could accurately discriminate between active tuberculosis and both latent and no M. tuberculosis infection, largely independently of (in)eligibility for highly active antiretroviral therapy (HAART). Six months after antituberculosis treatment, biomarker profiles of patients with tuberculosis became indistinguishable from those of patients with LTBI and controls. Importantly, host gene expression kinetics during antituberculosis treatment in HIV-coinfected individuals was found to be independent of HAART use. Conclusions: Blood transcriptomic profiles can potentially be used as biomarkers to discriminate the different clinical stages of tuberculosis in HIV-coinfected individuals and to monitor tuberculosis treatment responses in both HAART recipients and untreated individuals.

QuantiFERON-TB Gold In-tube test for the diagnosis of active and latent tuberculosis in selected health facilities of Addis Ababa, Ethiopia.

OBJECTIVE: To determine the performance of QuantiFERON-TB IN-Gold for the diagnosis active tuberculosis and latent tuberculosis. RESULTS: A total of 213 participants (136 tuberculosis suspects, 66 latently infected) were enrolled. Of 213, 21 (15.4%) of the tuberculosis suspects and 3 (4.5%) of the latent tuberculosis groups were human immunodeficiency virus infected. The sensitivity, specificity, positive and negative predictive value of QuantiFERON-TB IN-Gold for the diagnosis of active tuberculosis was 70.3% (26/37), 49.5% (49/99), 34.7% (26/75) and 83.1% (49/59) respectively. A kappa value of 0.316 (p = 0.001, 95% CI 1.605-1.609) between QuantiFERON-TB IN-Gold and tuberculin skin test were found.