Low rates of active hepatitis B and C infections among adults and children living with HIV and taking antiretroviral therapy: A multicenter screening study in Lesotho.

Lesotho presents the second-highest adult human immunodeficiency virus (HIV) prevalence globally. Among people living with HIV, data on hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection are limited. We report HBV and HCV coinfection data from a multicentre cross-sectional study among adult and pediatric patients taking antiretroviral therapy in 10 health facilities in Lesotho. Among 1318 adults screened (68% female; median age, 44 years), 262 (20%) had immunologically controlled HBV infection, 99 (7.6%) tested anti-HBs positive and anti-HBc negative, indicating vaccination, and 57 (4.3%) had chronic HBV infection. Among the patients with chronic HBV infection, 15 tested hepatitis B envelope antigen (HBeAg) positive and eight had detectable HBV viremia (median, 2 477 400 copies/mL; interquartile range, 205-34 400 000) with a mean aspartate aminotransferase-to-platelet ratio index of 0.48 (SD, 0.40). Prevalence of HCV coinfection was 1.7% (22 of 1318), and only one patient had detectable HCV viremia. Among 162 pediatric patients screened, three (1.9%) had chronic HBV infection, whereby two also tested HBeAg-positive, and one had detectable HBV viral load (210 copies/mL). Six of 162 (3.7%) had anti-HCV antibodies, all with undetectable HCV viral loads. Overall prevalence of chronic HBV/HIV and HCV/HIV coinfection among adults and children was relatively low, comparable to earlier reports from the same region. But prevalence of immunologically controlled HBV infection among adults was high. Of those patients with chronic HBV infection, a minority had detectable HBV-DNA.

Metabolic syndrome in patients on first-line antiretroviral therapy containing zidovudine or tenofovir in rural Lesotho, Southern Africa.

OBJECTIVE: To assess the prevalence of metabolic syndrome (MetS) among patients in rural Lesotho who are taking first-line antiretroviral therapy (ART) containing either zidovudine or tenofovir disoproxil. METHODS: Cross-sectional survey in 10 facilities in Lesotho among adult (≥16 years) patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART for ≥6 months. MetS was defined according to the International Diabetes Federation criteria. RESULTS: Among 1166 patients (65.8% female), 22.2% (95% CI: 19.3-25.3) of women and 6.3% (4.1-9.1) of men met the IDF definition of MetS (P < 0.001). In both sexes, there was no significant difference in MetS prevalence between NNRTIs. However, in women taking zidovudine as nucleoside reverse transcriptase inhibitor (NRTI), MetS prevalence was 27.9%, vs. 18.8% in those taking tenofovir. In the multivariate logistic regression allowing for socio-demographic and clinical covariates, ART containing zidovudine was associated with MetS in women (aOR 2.17 (1.46-3.22), P < 0.001) but not in men. CONCLUSION: In this study, taking ART containing zidovudine instead of tenofovir disoproxil was an independent predictor of MetS in women but not in men. This finding endorses WHO's recommendation of tenofovir as preferred NRTI.

Microscopic observation drug-susceptibility assay vs. Xpert® MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost-utility analysis.

OBJECTIVE: To compare the cost-utility of microscopic observation drug-susceptibility assay (MODS) and Xpert® MTB/RIF implementation for tuberculosis (TB) diagnosis in rural northern Mozambique. METHODS: Stochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and Xpert® MTB/RIF were evaluated as replacement test of smear microscopy (SM) or as an add-on test after a negative SM. Costs were calculated in 2013 USD, effects in disability-adjusted life years (DALY). Willingness to pay threshold (WPT) was established at once the per capita Gross National Income of Mozambique. RESULTS: MODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. Xpert® MTB/RIF as an add-on test to negative SM yielded ICER of 345.71USD/DALY averted. Xpert® MTB/RIF as a substitute for SM obtained an ICER of 122.13USD/DALY averted. TB prevalence and risk of infection were the main factors impacting MODS and Xpert® MTB/RIF ICER in the one-way sensitivity analysis. In the probabilistic sensitivity analysis, Xpert® MTB/RIF was most likely to have an ICER below the WPT, whereas MODS was not. CONCLUSION: Our cost-utility analysis favours the implementation of Xpert® MTB/RIF as a replacement of SM for all TB suspects in this rural high TB/HIV prevalence African setting.

Retention in care of HIV-infected pregnant and lactating women starting ART under Option B+ in rural Mozambique.

OBJECTIVE: In 2013, Mozambique adopted Option B+, universal lifelong antiretroviral therapy (ART) for all pregnant and lactating women, as national strategy for prevention of mother-to-child transmission of HIV. We analysed retention in care of pregnant and lactating women starting Option B+ in rural northern Mozambique. METHODS: We compared ART outcomes in pregnant ('B+ pregnant'), lactating ('B+ lactating') and non-pregnant non-lactating women of childbearing age starting ART according to clinical and/or immunological criteria ('own health') between July 2013 and June 2014. Lost to follow-up was defined as no contact >180 days after the last visit. Multivariable competing risk models were adjusted for type of facility (type 1 vs. peripheral type 2 health centre), age, WHO stage and time from HIV diagnosis to ART. RESULTS: Over 333 person-years of follow-up (243 'B+ pregnant', 65'B+ lactating' and 317 'own health' women), 3.7% of women died and 48.5% were lost to follow-up. 'B+ pregnant' and 'B+ lactating' women were more likely to be lost in the first year (57% vs. 56.9% vs. 31.6%; P < 0.001) and to have no follow-up after the first visit (42.4% vs. 29.2% vs. 16.4%; P < 0.001) than 'own health' women. In adjusted analyses, risk of being lost to follow-up was higher in 'B+ pregnant' (adjusted subhazard ratio [asHR]: 2.77; 95% CI: 2.18-3.50; P < 0.001) and 'B+ lactating' (asHR: 1.94; 95% CI: 1.37-2.74; P < 0.001). Type 2 health centre was the only additional significant risk factor for loss to follow-up. CONCLUSIONS: Retention among PLW starting option B+ ART was poor and mainly driven by early losses. The success of Option B+ for prevention of mother-to-child transmission of HIV in rural settings with weak health systems will depend on specific improvements in counselling and retention measures, especially at the beginning of treatment.

Home-based versus mobile clinic HIV testing and counseling in rural Lesotho: a cluster-randomized trial.

BACKGROUND: The success of HIV programs relies on widely accessible HIV testing and counseling (HTC) services at health facilities as well as in the community. Home-based HTC (HB-HTC) is a popular community-based approach to reach persons who do not test at health facilities. Data comparing HB-HTC to other community-based HTC approaches are very limited. This trial compares HB-HTC to mobile clinic HTC (MC-HTC). METHODS AND FINDINGS: The trial was powered to test the hypothesis of higher HTC uptake in HB-HTC campaigns than in MC-HTC campaigns. Twelve clusters were randomly allocated to HB-HTC or MC-HTC. The six clusters in the HB-HTC group received 30 1-d multi-disease campaigns (five villages per cluster) that delivered services by going door-to-door, whereas the six clusters in MC-HTC group received campaigns involving community gatherings in the 30 villages with subsequent service provision in mobile clinics. Time allocation and human resources were standardized and equal in both groups. All individuals accessing the campaigns with unknown HIV status or whose last HIV test was >12 wk ago and was negative were eligible. All outcomes were assessed at the individual level. Statistical analysis used multivariable logistic regression. Odds ratios and p-values were adjusted for gender, age, and cluster effect. Out of 3,197 participants from the 12 clusters, 2,563 (80.2%) were eligible (HB-HTC: 1,171; MC-HTC: 1,392). The results for the primary outcomes were as follows. Overall HTC uptake was higher in the HB-HTC group than in the MC-HTC group (92.5% versus 86.7%; adjusted odds ratio [aOR]: 2.06; 95% CI: 1.18-3.60; p = 0. 011). Among adolescents and adults ≥ 12 y, HTC uptake did not differ significantly between the two groups; however, in children <12 y, HTC uptake was higher in the HB-HTC arm (87.5% versus 58.7%; aOR: 4.91; 95% CI: 2.41-10.0; p<0.001). Out of those who took up HTC, 114 (4.9%) tested HIV-positive, 39 (3.6%) in the HB-HTC arm and 75 (6.2%) in the MC-HTC arm (aOR: 0.64; 95% CI: 0.48-0.86; p = 0.002). Ten (25.6%) and 19 (25.3%) individuals in the HB-HTC and in the MC-HTC arms, respectively, linked to HIV care within 1 mo after testing positive. Findings for secondary outcomes were as follows: HB-HTC reached more first-time testers, particularly among adolescents and young adults, and had a higher proportion of men among participants. However, after adjusting for clustering, the difference in male participation was not significant anymore. Age distribution among participants and immunological and clinical stages among persons newly diagnosed HIV-positive did not differ significantly between the two groups. Major study limitations included the campaigns' restriction to weekdays and a relatively low HIV prevalence among participants, the latter indicating that both arms may have reached an underexposed population. CONCLUSIONS: This study demonstrates that both HB-HTC and MC-HTC can achieve high uptake of HTC. The choice between these two community-based strategies will depend on the objective of the activity: HB-HTC was better in reaching children, individuals who had never tested before, and men, while MC-HTC detected more new HIV infections. The low rate of linkage to care after a positive HIV test warrants future consideration of combining community-based HTC approaches with strategies to improve linkage to care for persons who test HIV-positive. TRIAL REGISTRATION: ClinicalTrials.gov NCT01459120. Please see later in the article for the Editors' Summary.

Microscopic observation drug susceptibility assay for the diagnosis of TB and MDR-TB in HIV-infected patients: a systematic review and meta-analysis.

The objective of the present study was to assess the diagnostic accuracy of the microscopic observation drug susceptibility (MODS) assay for tuberculosis (TB) diagnosis in HIV-infected patients. MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, African Index Medicus, ResearchGate, SciELO, and the abstracts of the main conferences on infectious diseases and tropical medicine were searched, and other sources investigated. Only studies including HIV-infected patients evaluating MODS for the diagnosis of TB and using culture-based diagnostic tests as a gold standard were analysed. Summary sensitivity and specificity were calculated with a bivariate model. 3259 citations were found, 29 were selected for full-text review and 10 studies including 3075 samples were finally analysed. Overall diagnostic accuracy of MODS for the diagnosis of TB was a sensitivity of 88.3% (95% CI 86.18-90.2%) and specificity 98.2% (95% CI 97.75-98.55%). For multidrug-resistant (MDR)-TB, sensitivity was 89% (95% CI 66.07-97%) and specificity was 100% (95 CI 94.81-100%). For smear-negative pulmonary TB, a sensitivity of 88.2% (95% CI 86.1-89.9%) and specificity of 98.2% (95% CI 96.8-98.9%) were found. Costs varied between USD 0.72 and 7.31 per sample. Mean time to positivity was 8.24 days. MODS was found to have a good accuracy for the diagnosis of TB and MDR-TB in HIV-infected patients with low cost and fast results.

Effect of the Friendship Bench intervention on antiretroviral therapy outcomes and mental health symptoms in rural Zimbabwe: A cluster randomized trial.

Importance: Common mental disorders (CMD) are prevalent in people living with HIV and associated with suboptimal antiretroviral therapy (ART) adherence. Objective: To assess the effect of a lay health worker-led psychological intervention on adherence to ART, virologic suppression and mental health symptoms. Design: Pragmatic cluster trial with block randomization of health facilities. Treatment assignment was known to participants, providers, evaluators, and data analysts. Recruitment started in October 2018 and the last follow-up visit was done in December 2020. Participants were followed up for 12 months. Setting: Sixteen public health care facilities in Bikita, a rural district in Masvingo Province, about 300 km south of Harare. Participants: Men and non-pregnant women aged 18 years or older who spoke English or Shona, screened positive for CMD (Shona Symptoms Questionnaire [SSQ]-14 score ≥9), had received first-line ART for at least six months, had no WHO clinical stage 4 disease, no psychotic symptoms, and gave informed consent. Intervention: The Friendship Bench, a lay health worker-led intervention consisting of six weekly individual counselling sessions of problem-solving therapy and optional peer-led group support. Main Outcomes and Measures: The primary outcome was Medication Event Monitoring System (MEMS) mean adherence between 2-6 months of follow-up. Secondary outcomes included mean adherence between 1-12 months, change from baseline SSQ-14 and Patient Health Questionnaire (PHQ-9) score at 3, 6, 9, and 12 months and change in viral load suppression (viral load <1000 copies per mL) at months 6 and 12. Results: We recruited 516 participants, 244 in Friendship bench and 272 in standard care facilities. The mean age was 45.6 years (SD 10.9), and most participants were women (84.9%). In the Friendship Bench group, 88.1% of participants attended all six individual counselling sessions. Rates of adherence (>85%) and virologic suppression (>90%) were high in both groups. The intervention had no statistically significant effect on adherence or viral suppression. Declines in SSQ-14 scores from baseline to 3 months (-1.65, 95% CI -3.07 to -0.24), 6 months (-1.57, 95% CI -2.98 to -0.15), and 9 months (-1.63, 95% CI -3.05 to -0.22) were greater in the Friendship Bench than the standard care group (p<0.05). There were no differences in the decline in the SSQ-14 scores from baseline to 12 months and in declines in PHQ-9 scores from baseline to 3, 6, 9, and 12 months. Conclusions and Relevance: The Friendship Bench intervention is a feasible and acceptable approach to closing the treatment gap in mental health care in rural Zimbabwe. The intervention improved CMD symptoms but the intervention effect was smaller than previously shown in an urban setting. The intervention had no effect on adherence and viral suppression, possibly due to the absence of skill-based adherence training and ceiling effect. Trial registration: ClinicalTrials.gov Identifier: NCT03704805. Key points: Question: Does the Friendship Bench intervention improve antiretroviral therapy (ART) adherence, viral suppression and mental health symptoms in people living with HIV in rural Zimbabwe?Findings: In this cluster-randomized trial, participants in the intervention group had a significantly greater decrease in symptoms of common mental disorders than those in the control group, but the intervention showed no significant effect on antiretroviral therapy (ART) adherence or viral suppression.Meaning: The intervention did not affect adherence and viral suppression and the effect of the intervention on mental health symptoms was smaller than previously shown.

Effect of the Friendship Bench Intervention on Antiretroviral Therapy Outcomes and Mental Health Symptoms in Rural Zimbabwe: A Cluster Randomized Trial.

Importance: Common mental disorders (CMD), which include depression and anxiety, are prevalent among people living with HIV and are associated with suboptimal antiretroviral therapy (ART) adherence. Objective: To assess the effect of a lay health worker-led psychological intervention on ART adherence, virologic suppression, and mental health symptoms. Design, Setting, and Participants: Open-label pragmatic cluster trial with 1:1 block randomization of 16 health facilities in rural Bikita, Zimbabwe. Recruitment occurred from October 2018 to December 2019, and participants were followed up for 12 months, ending in December 2020. Participants were adults aged 18 years and older, who spoke English or Shona, screened positive for CMD (Shona Symptoms Questionnaire [SSQ]-14 score ≥9), received first-line ART for 6 or more months, had no World Health Organization stage 4 disease, no psychosis, were not pregnant, and provided informed consent. Data were analyzed from March 2021 to February 2022. Intervention: The Friendship Bench, consisting of 6 lay health worker-led weekly problem-solving therapy sessions and optional peer-led group support. Main Outcomes and Measures: The primary outcome was mean adherence during 2 to 6 months of follow-up, and the secondary outcomes were mean adherence during 1 to 12 months of follow-up, change in SSQ-14 and Patient Health Questionnaire (PHQ-9) scores (3, 6, 9, and 12 months), and viral load suppression (6 and 12 months). Results: A total of 516 participants were recruited (244 in Friendship Bench and 272 in enhanced standard care facilities); 438 (84.9%) were female and the mean (SD) age was 45.6 (10.9) years. Mean (SD) adherence between 2 to 6 months was 89.9% (18.4%) in the Friendship Bench group and 87.2% (20.1%) in the control group. The intervention had no statistically significant effect on adherence between 2 to 6 months (unadjusted mean difference, 1.93 percentage points; 95% CI, -1.20 to 5.06 percentage points; P = .23), between months 1 to 12 (mean difference 0.79 percentage points; 95% CI, -2.14 to 3.71 percentage points; P = .60), or viral suppression. Declines in SSQ-14 scores from baseline to 3 months (difference, -1.65; 95% CI, -3.07 to -0.24), 6 months (difference, -1.57; 95% CI, -2.98 to -0.15), and 9 months (difference, -1.63; 95% CI, -3.05 to -0.22) were greater in the Friendship Bench than the standard care group (P < .05). There were no differences in the decline in the SSQ-14 scores from baseline to 12 months and in declines in PHQ-9 scores from baseline to 3, 6, 9, and 12 months. Conclusions and Relevance: In this randomized trial of HIV-positive participants with CMD, the Friendship Bench intervention had no effect on adherence and viral suppression, possibly due to the absence of skill-based adherence training and a ceiling effect. Trial Registration: ClinicalTrials.gov Identifier: NCT03704805.

Symptoms of common mental disorders and adherence to antiretroviral therapy among adults living with HIV in rural Zimbabwe: a cross-sectional study.

OBJECTIVES: To examine the proportion of people living with HIV who screen positive for common mental disorders (CMD) and the associations between CMD and self-reported adherence to antiretroviral therapy (ART). SETTING: Sixteen government-funded health facilities in the rural Bikita district of Zimbabwe. DESIGN: Cross-sectional study. PARTICIPANTS: HIV-positive non-pregnant adults, aged 18 years or older, who lived in Bikita district and had received ART for at least 6 months. OUTCOME MEASURES: The primary outcome was the proportion of participants screening positive for CMD defined as a Shona Symptoms Questionnaire score of 9 or greater. Secondary outcomes were the proportion of participants reporting suicidal ideation, perceptual symptoms and suboptimal ART adherence and adjusted prevalence ratios (aPR) for factors associated with CMD, suicidal ideation, perceptual symptoms and suboptimal ART adherence. RESULTS: Out of 3480 adults, 18.8% (95% CI 14.8% to 23.7%) screened positive for CMD, 2.7% (95% CI 1.5% to 4.7%) reported suicidal ideations, and 1.5% (95% CI 0.9% to 2.6%) reported perceptual symptoms. Positive CMD screens were more common in women (aPR 1.67, 95% CI 1.19 to 2.35) than in men and were more common in adults aged 40-49 years (aPR 1.47, 95% CI 1.16 to 1.85) or aged 50-59 years (aPR 1.51, 95% CI 1.05 to 2.17) than in those 60 years or older. Positive CMD screen was associated with suboptimal adherence (aPR 1.53; 95% CI 1.37 to 1.70). CONCLUSIONS: A substantial proportion of people living with HIV in rural Zimbabwe are affected by CMD. There is a need to integrate mental health services and HIV programmes in rural Zimbabwe. TRIAL REGISTRATION NUMBER: NCT03704805.

Loss to follow-up correction increased mortality estimates in HIV-positive people on antiretroviral therapy in Mozambique.

OBJECTIVES: People living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) may be lost to follow-up (LTFU), which hampers the assessment of outcomes. We estimated mortality for patients starting ART in a rural region in sub-Saharan Africa and examined risk factors for death, correcting for LTFU. STUDY DESIGN AND SETTING: We analyzed data from Ancuabe, Mozambique, where patients LTFU are traced by phone and home visits. We used cumulative incidence functions to estimate mortality and LTFU. To correct for LTFU, we revised outcomes based on tracing data using different inverse probability weights (maximum likelihood, Ridge regression, or Bayesian model averaging). We fitted competing risk models to identify risk factors for death and LTFU. RESULTS: The analyses included 4,492 patients; during 8,152 person-years of follow-up, 486 patients died, 2,375 were LTFU, 752 were traced, and 603 were found. At 4 years after starting ART, observed mortality was 11.9% (95% confidence interval [CI]: 10.9-13.0), but 23.5% (95% CI: 19.8-28.0), 21.6% (95% CI: 18.7-25.0), and 23.3% (95% CI: 19.7-27.6) after correction with maximum likelihood, Ridge regression, and Bayesian model averaging weights, respectively. The risk factors for death included male sex, lower CD4 cell counts, and more advanced clinical stage. CONCLUSION: In ART programs with substantial LTFU, mortality estimates need to take LTFU into account.

Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa.

BACKGROUND: Using data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH). METHODS: We included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10-19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10-13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models. RESULTS: Overall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10-13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10-13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10-13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10-13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42). CONCLUSION: Retention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10-13 vs. less than 10 years.

Characterizing the double-sided cascade of care for adolescents living with HIV transitioning to adulthood across Southern Africa.

INTRODUCTION: As adolescents and young people living with HIV (AYLH) age, they face a "transition cascade," a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where "transition" may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when "transition" to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. METHODS: We included AYLH aged <16 years at enrolment, receiving antiretroviral therapy (ART) within International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) sites (2004 to 2017) with no history of transferring care. Using the ages of 16, 18, 20 and 22 years as proxies for "transition to autonomy," we compared the outcomes: no gap in care (≥2 clinic visits) and viral suppression (HIV-RNA <400 copies/mL) in the 12 months before and after each age threshold. Using log-binomial regression, we examined factors associated with no gap in care (retention) in the 12 months post-transition. RESULTS: A total of 5516 AYLH from 16 sites were included at "transition" age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y, in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y: adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). CONCLUSIONS: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood.

Demand-side financing in the form of baby packages in Northern Mozambique: Results from an observational study.

BACKGROUND: The Maternal Mortality Ratio in Mozambique has stagnated at 405 deaths per 100,000 live births with virtually no progress over the last 15 years. Low Institutional Birth Rates (IBRs) levelling around 50% in many rural areas constitute one of the contributing reasons. Demand-side financing has successfully increased usage of maternal health services in other countries, but little information exists on in-kind incentives in rural Africa. The objective was to test the impact on Institutional Birth Rates of giving a USD 5.50 baby package incentive to every woman who came to give birth in a health centre in a rural, poor district of Cabo Delgado, Mozambique. METHODS AND FINDINGS: The intervention was implemented in one district in 2010 with the remaining 15 districts serving as controls. The total population in the 16 districts in 2006 was just under 1.5 million people. IBRs were observed from 2006 to 2013 (53 months before and 55 months after the intervention began). The non-intervention districts showed a slight increase, from a mean IBR of 0.39 (SD = 0.10) in 2006 to 0.67 (SD = 0.13) in 2014. The intervention district had a dramatic increase in IBRs within six months of the start of the intervention in 2010, which was sustained until the end of the study. Adjusting for the background increase and for confounders, including health facilities and health personnel per district, and taking clustering in districts into account, the estimated rate ratio of institutional births in the intervention district was 1.80 (95% CI 1.72, 1.89 p<0.001). CONCLUSION: Women were almost twice as likely to have an institutional birth following the introduction of the baby package.

Triage conducted by lay-staff and emergency training reduces paediatric mortality in the emergency department of a rural hospital in Northern Mozambique.

INTRODUCTION: The majority of emergency paediatric death in African countries occur within the first 24 h of admission. A coloured triage system is widely implemented in high-income countries and the emergency triage and assessment treatment (ETAT) is recommended by the World Health Organization, but not put into practice in Mozambique. We implemented a three-colour triage system in a rural district hospital with lay-staff workers conducting the first triage. METHODS: A retrospective, before and after, mortality analysis was performed using routine patient files from the district hospital between 2014 and 2017. The triage system was implemented in August 2016. Inclusion criteria were children under 15 years of age that entered the emergency centre. Primary outcome was child mortality rate. Secondary outcomes included the percentage agreement between the clinical and non-clinical staff and the duration from triage to first treatment. We used a negative binomial model in STATA 15 to compare mortality rates, and Kappa statistics to estimate the agreement between clinical and non-clinical staff. RESULTS: 4176 admissions were included. The mortality rate ratio (MMR) was 45% lower after the start of the intervention (2016; MRR = 0.55; 0.38, 0.81; p = 0.002), compared to before. To estimate the agreement between non-clinical and clinical staff, 548 (of the 671) patient files were included. The agreement was estimated at 88.7% (Kappa = 0.644; p < 0.001). The median waiting time decreased with urgency of the triage: 2 h33 for 'green'/least serious (IQR 1 h58-3 h30), 21 min for yellow/serious (IQR 0 h10-0 h58) and nine minutes for 'red'/urgent (IQR 2-40 min). CONCLUSION: In a rural setting with nurse-led clinical care and non-clinician staff working at the triage reception, implementation of a three-coloured triage system was feasible. Triage and ETAT training was associated with a decrease of 45% of paediatric deaths. The impact on mortality, low cost, and ease of the implementation supports scaling this intervention in similar settings.

Extending Visit Intervals for Clinically Stable Patients on Antiretroviral Therapy: Multicohort Analysis of HIV Programs in Southern Africa.

BACKGROUND: The World Health Organization recommends differentiated antiretroviral therapy (ART) delivery with longer visit intervals for clinically stable patients. We examined time trends in visit frequency and associations between criteria for clinical stability and visit frequency in ART programs in Southern Africa. METHODS: We included adults on ART from 4 programs with viral-load monitoring, 2 programs with CD4 monitoring, and 4 programs with clinical monitoring of ART. We classified patients as clinically stable based on virological (viral load <1000 copies/mL), immunological (CD4 >200 cells/µL), or clinical (no current tuberculosis) criteria. We used Poisson regression and survival models to examine associations between criteria for clinical stability and the rate of clinic visits. RESULTS: We included 180,837 patients. There were trends toward fewer visits in more recent years and with longer ART duration. In all ART programs, clinically stable patients were seen less frequently than patients receiving failing ART, but the strength of the association varied. Adjusted incidence rate ratios comparing visit rates for stable patients with patients on failing ART were 0.82 (95% confidence interval: 0.73 to 0.90) for patients classified based on the virological criterion, 0.81 (0.69 to 0.93) for patients classified based on the clinical criterion, and 0.90 (0.85 to 0.96) for patients classified based on the immunological criterion for stability. CONCLUSION: Differences in visit rates between stable patients and patients failing ART were variable and modest overall. Larger differences were seen in programs using virological criteria for clinical stability than in programs using immunological criteria. Greater access to routine viral-load monitoring may increase scale-up of differentiated ART delivery.

Acceptability and performance of a directly assisted oral HIV self-testing intervention in adolescents in rural Mozambique.

INTRODUCTION: Whereas progress in HIV testing and treatment has been made globally, the UNAIDS goal of "90 90 90" is still out of sight in rural northern Mozambique. New strategies that promote testing in hard to reach groups will aid Mozambique's response to the HIV epidemic. HIV self-testing (HIVST) is recommended by the WHO as an additional approach to augment the HIV testing services available to adolescents. This study evaluates acceptability and performance of a directly assisted oral HIVST intervention for adolescents in rural Mozambique. METHODS: Adolescents aged 16-20 years were included at schools and invited to attend the local hospital's youth friendly service for directly assisted oral HIVST. Baseline and post-test questionnaires were obtained. OraQuick Rapid HIV-1/2 Anti body test® was used. Results were read by the participant and by a nurse. Results were confirmed by finger prick HIV test (Determine® HIV 1/2 Alere and Unigold™ HIV Trinity Biotech) according to the Mozambican national standard. RESULTS: Between September and November 2016, 496 adolescents were included, of which 299 performed an oral HIV self-test. 70% were first time testers. The positivity rate was 1.7%. The inter-rater agreement between adolescent and nurse was 99.6% (kappa 0.93); there were no false negative or false positive results of the oral HIV self-test. Five tests were invalid. 7.1% found the test difficult to use. Over 80% preferred directly assisted HIVST compared to the standard finger prick testing. While 20% thought it would be good to do HIVST at home, 76% preferred to do HIVST at the health centre, for reasons including increased security, privacy, and the presence of a counsellor. CONCLUSIONS: Directly assisted oral HIVST is a feasible intervention for adolescents in rural Mozambique and showed encouraging results for first time HIV testers.

Drought risk assessment under climate change is sensitive to methodological choices for the estimation of evaporative demand.

Several studies have projected increases in drought severity, extent and duration in many parts of the world under climate change. We examine sources of uncertainty arising from the methodological choices for the assessment of future drought risk in the continental US (CONUS). One such uncertainty is in the climate models' expression of evaporative demand (E0), which is not a direct climate model output but has been traditionally estimated using several different formulations. Here we analyze daily output from two CMIP5 GCMs to evaluate how differences in E0 formulation, treatment of meteorological driving data, choice of GCM, and standardization of time series influence the estimation of E0. These methodological choices yield different assessments of spatio-temporal variability in E0 and different trends in 21st century drought risk. First, we estimate E0 using three widely used E0 formulations: Penman-Monteith; Hargreaves-Samani; and Priestley-Taylor. Our analysis, which primarily focuses on the May-September warm-season period, shows that E0 climatology and its spatial pattern differ substantially between these three formulations. Overall, we find higher magnitudes of E0 and its interannual variability using Penman-Monteith, in particular for regions like the Great Plains and southwestern US where E0 is strongly influenced by variations in wind and relative humidity. When examining projected changes in E0 during the 21st century, there are also large differences among the three formulations, particularly the Penman-Monteith relative to the other two formulations. The 21st century E0 trends, particularly in percent change and standardized anomalies of E0, are found to be sensitive to the long-term mean value and the amplitude of interannual variability, i.e. if the magnitude of E0 and its interannual variability are relatively low for a particular E0 formulation, then the normalized or standardized 21st century trend based on that formulation is amplified relative to other formulations. This is the case for the use of Hargreaves-Samani and Priestley-Taylor, where future E0 trends are comparatively much larger than for Penman-Monteith. When comparing Penman-Monteith E0 responses between different choices of input variables related to wind speed, surface roughness, and net radiation, we found differences in E0 trends, although these choices had a much smaller influence on E0 trends than did the E0 formulation choices. These methodological choices and specific climate model selection, also have a large influence on the estimation of trends in standardized drought indices used for drought assessment operationally. We find that standardization tends to amplify divergences between the E0 trends calculated using different E0 formulations, because standardization is sensitive to both the climatology and amplitude of interannual variability of E0. For different methodological choices and GCM output considered in estimating E0, we examine potential sources of uncertainty in 21st century trends in the Standardized Precipitation Evapotranspiration Index (SPEI) and Evaporative Demand Drought Index (EDDI) over selected regions of the CONUS to demonstrate the practical implications of these methodological choices for the quantification of drought risk under climate change.

Should viral load thresholds be lowered?: Revisiting the WHO definition for virologic failure in patients on antiretroviral therapy in resource-limited settings.

The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with <1000 copies/mL. The positive predictive value (PPV) for the WHO failure definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be considered.

Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique.

Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication.

Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia.

BACKGROUND: Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS: We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS: Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/µl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. CONCLUSION: One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.