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Objectives: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems., Methods: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses., Results: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030., Conclusions: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT., (© 2020 John Wiley & Sons Ltd.)

Objective: To determine clinical correlates of the peripheral absolute eosinophil count (AEC) among bacteriologically confirmed TB patients in Uganda., Materials and Methods: We evaluated data of bacteriologically confirmed adult TB patients who had a peripheral blood AEC measurement at the National TB Treatment Center in Uganda during a cross-sectional study. We performed linear regression analysis for correlates of log-transformed AEC., Results: We included 235 patients in this analysis with a median (interquartile range, IQR) age of 31 (24-39) years. 60.4% were male, and 33.6% had TB/HIV co-infection. In a multivariable linear regression model that controlled for age, residence type, HIV status, weight loss, anorexia, body mass index, CD8+ T-cell count, haemoglobin level and TB bacillary load, males had a 47.0% higher AEC than females (adjusted coefficient (R 2 ) = 0.385, 95% confidence interval (CI) 0.012-0.759 P = 0.043). Also, a 1 °C raise in temperature resulted in an 11.5% decrease in the AEC (R 2  = -0.122 95% CI (-0.233 to -0.011) P = 0.031) while a 1 cell/mm 3 increase in the CD4+ T-cell count resulted in a 0.10% increase in the AEC (R 2  = 0.001 95% CI (0.000-0.001) P = 0.032)., Conclusion: The AEC was higher among males than females, consistent with the normal population distribution of AEC among Ugandans. The AEC was weakly but positively correlated with the CD4 count and negatively correlated with temperature., (© 2020 John Wiley & Sons Ltd.)

Objectives: To examine the association between aflatoxin (AF) exposure during pregnancy and rate of gestational weight gain (GWG) in a sample of pregnant women of mixed HIV status in Gulu, northern Uganda., Methods: 403 pregnant women were included (133 HIV-infected on antiretroviral therapy (ART), 270 HIV-uninfected). Women's weight, height and socio-demographic characteristics were collected at baseline (~19 weeks' gestation); weight was assessed at each follow-up visit. Serum was collected at baseline and tested for aflatoxin B 1 -lysine adduct (AFB-lys) levels using high-performance liquid chromatography (HPLC). Linear mixed-effects models were used to examine the association between AFB-lys levels and rate of GWG., Results: AFB-lys levels (detected in 98.3% of samples) were higher among HIV-infected pregnant women than HIV-uninfected pregnant women [median (interquartile range): 4.8 (2.0, 15.0) vs. 3.5 (1.6, 6.1) pg/mg of albumin, P < 0.0001]. Adjusting for HIV status, a one-log increase in aflatoxin levels was associated with a 16.2 g per week lower rate of GWG (P = 0.028). The association between AFB-lys and the rate of GWG was stronger and significant only among HIV-infected women on ART [-25.7 g per week per log (AFB-lys), P = 0.009 for HIV-infected women vs. -7.5 g per week per log (AFB-lys), P = 0.422 for HIV-uninfected women]., Conclusions: Pregnant women with higher levels of AF exposure had lower rates of GWG. The association was stronger for HIV-infected women on ART, suggesting increased risk., (© 2020 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objectives: HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV., Methods: The study was a retrospective cohort study (study period 2004-2018). Cases of HIV + and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV + controls without SCD (HIV+/SCD-)., Results: Thirty-five HIV+/SCD + subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6 years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD + had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P = 0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD + and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD + cohort (P = 0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD + cohort showed a more rapid rise and higher total CD4 count (P = 0.012, regression analysis)., Conclusion: The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD + achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression., (© 2020 John Wiley & Sons Ltd.)

Objectives: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil., Methods: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014., Results: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm 3 vs. >250 cells/mm 3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01)., Conclusions: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands., (© 2020 John Wiley & Sons Ltd.)

Objective: To compare the prevalence of tuberculosis infection and disease in household contacts of patients with bacteriologically confirmed tuberculosis disease and contacts of non-bacteriologically confirmed disease in western Kenya., Methods: We enrolled newly diagnosed index patients and their household contacts from March 2014 to June 2016. All contacts were evaluated with a symptom questionnaire, tuberculin skin test (TST) and HIV test. Clinical evaluation and sputum testing were performed for those with symptoms, positive TST result or HIV infection., Results: We enrolled 1155 contacts of 330 index patients with bacteriologically confirmed tuberculosis and 192 contacts of 55 index patients with non-bacteriologically confirmed tuberculosis. 3.5% of contacts of patients with bacteriologically confirmed tuberculosis were diagnosed with tuberculosis, whereas no contacts of index patients with non-bacteriologically confirmed tuberculosis were. Of those diagnosed with tuberculosis disease, 58.5% reported symptoms, 34.1% reported no symptoms but had positive TST results, and 7.3% had neither symptoms nor positive TST but were HIV-positive. Among 872 contacts with a TST result, 50.9% of contacts of index patients with bacteriologically confirmed tuberculosis and 41.0% of contacts of index patients with non-bacteriologically confirmed tuberculosis had a positive result (prevalence ratio = 1.16, 95% confidence interval 0.92-1.48)., Conclusion: In a high-burden setting, tuberculosis disease was more prevalent among contacts of patients with bacteriologically confirmed tuberculosis than contacts of patients with non-bacteriologically confirmed disease. TST was feasible to perform and helped to detect cases that would have been missed had only symptomatic contacts been evaluated., (© 2020 John Wiley & Sons Ltd.)

Objectives: WHO recommends HIV self-testing (HIVST) as an additional approach to HIV testing services. The study describes the strategies used during phase-in of HIVST under routine conditions in Eswatini (formerly Swaziland)., Methods: Between May 2017 and January 2018, assisted and unassisted oral HIVST was offered at HIV testing services (HTS) sites to people aged ≥ 16 years. Additional support tools were available, including a telephone hotline answered 24/7, HIVST demonstration videos and printed educational information about HIV prevention and care services. Demographic characteristics of HIVST users were described and compared with standard blood-based HTS in the community. HIVST results were monitored with follow-up phone calls and the hotline., Results: During the 9-month period, 1895 people accessed HIVST and 2415 HIVST kits were distributed. More people accessed HIVST kits in the community (n = 1365, 72.0%) than at health facilities (n = 530, 28.0%). The proportion of males and median age among those accessing HIVST and standard HTS in the community were similar (49.3%, 29 years HIVST vs. 48.7%, 27 years standard HTS). In total, 34 (3.9%) reactive results were reported from 938 people with known HIVST results; 32.4% were males, and median age was 30 years (interquartile range 25-36). Twenty-one (62%) patients were known to have received confirmatory blood-based HTS; of these, 20 (95%) had concordant reactive results and 19 (95%) were linked to HIV care at a clinic., Conclusion: Integration of HIVST into existing HIV facility- and community-based testing strategies in Eswatini was found to be feasible, and HIVST has been adopted by national testing bodies in Eswatini., (© 2020 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objective: To describe the features of HIV-associated chronic lung disease (CLD) in older children and adolescents living with HIV and to examine the clinical factors associated with CLD. This is a post hoc analysis of baseline data from the BREATHE clinical trial (ClinicalTrials.gov, NCT02426112)., Methods: Children and adolescents aged 6-19 years were screened for CLD (defined as a FEV1 z-score <-1 with no reversibility post-bronchodilation with salbutamol) at two HIV clinics in Harare, Zimbabwe, and Blantyre, Malawi. Eligible participants with CLD (cases) were enrolled, together with a control group without CLD [frequency-matched by age group and duration on antiretroviral therapy (ART)] in a 4:1 allocation ratio. A clinical history and examination were undertaken. The association between CLD and a priori-defined demographic and clinical covariates was investigated using multivariable logistic regression., Results: Of the 1585 participants screened, 419 (32%) had a FEV1 z-score <-1, of whom 347 were enrolled as cases [median age 15.3 years (IQR 12.7-17.7); 48.9% female] and 74 with FEV1 z-score >0 as controls [median age 15.6 years (IQR 12.1-18.2); 62.2% female]. Among cases, current respiratory symptoms including cough and shortness of breath were reported infrequently (9.3% and 1.8%, respectively). However, 152 (43.8%) of cases had a respiratory rate above the 90th centile for their age. Wasting and taking second-line ART were independently associated with CLD., Conclusions: The presence of CLD indicates the need to address additional treatment support for youth living with HIV, alongside ART provision, to ensure a healthier adulthood., (© 2020 John Wiley & Sons Ltd.)

Objective: Early identification of confirmed virological failure is paramount to avoid accumulation of drug resistance in patients on antiretroviral therapy (ART). Scale-up of HIV-RNA monitoring in Africa and timely switch to second-line regimens are challenged., Methods: A WHO adapted confirmed virological treatment screening algorithm (HIV-RNA screening, enhanced adherence counselling, confirmatory HIV-RNA testing) was evaluated in HIV-infected patients on first-line ART from Tanzania. The main endpoints included viral resuppression and virological failure rates, retention and turnaround time of the screening algorithm until second-line ART initiation. Secondary endpoints included risk factors for virological treatment failure and patterns of genotypic drug resistance., Results: HIV-RNA >1000 copies/ml at first screening was detected in 58/356 (16.3%) patients (median time-on-treatment 6.3 years, 25% immunological treatment failure). Adjusted risk factors for virological failure were age <30 years (RR 5.2 [95% CI: 2.5-10.8]), years on ART ≥3 years (RR 3.0 [1.0-8.9]), CD4-counts <200 cells/µl (RR 9.3 [4.0-21.8]) and poor self-reported treatment adherence (RR 2.0 [1.2-3.4]). Resuppression of HIV-RNA <1000 copies/ml was observed in 5/50 (10%) cases after enhanced adherence counselling. Confirmatory testing within 3 months was performed in only 46.6% and switch to second-line ART within 6 months in 60.4% of patients. Major NNRTI-mutation were detected in all of 30 patients, NRTI mutations in 96.7% and ≥3 thymidine-analogue mutations in 40%. No remaining NRTI options were predicted in 57% and limited susceptibility in 23% of patients., Conclusion: We observed low levels of viral resuppression following adherence counselling, associated with high levels of accumulated drug resistance. High visit burden and turnaround times for confirmed virological failure diagnosis further delayed switching to second-line treatment which could be improved using novel point-of-care viral load monitoring systems., (© 2020 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objective: Tailored services for adolescents and young adults (AYA) living with HIV may improve treatment outcomes. We surveyed HIV clinics throughout Kenya to determine AYA clinic practices, disclosure and transition services., Methods: We deployed a mobile team to conduct surveys in a random sample of 102 public HIV clinics with> 300 total clients. Data were collected from healthcare workers offering AYA services who had >6 months of experience delivering AYA care., Results: Of 102 surveyed HIV clinics, almost all (101/102) had the same staff to provide services to all age groups. AYA-specific services included dedicated clinic days (91%), the majority being on weekends (57%) and designated clinic spaces (20%). Activities to support AYA retention and adherence were common (support groups [97%] and HIV literacy meetings [93%]). Fewer clinics offered more holistic care, including psychosocial support (16%) and career education (2%), posted additional staff during the AYA day (17%), provided food (17%) or had sporting activities (10%) as incentives. Tracking of disclosure of HIV status to AYA was common (87%). In 40% of clinics, disclosure discussions with caregivers or AYA occurred a median of 2 years later in practice than stated in clinic policy. Transition was not routinely tracked, and definitions were heterogeneous. Median age at transition was reported as 20 years (range: 14-30 years)., Conclusion: HIV programmes have implemented varied approaches to enhance AYA services that could be leveraged to support transition to adult services. Research on the impact of these services on health outcomes is needed., (© 2020 John Wiley & Sons Ltd.)

Background: High demand for HIV-services and extensive clinical guidelines force health systems in low-resource settings to dedicate resources to service delivery at the expense of other priorities. Simplifying services may reduce the burden on health systems and pre-antiretroviral therapy (ART) laboratory screening is among the services under consideration for simplification., Methods: We assessed the frequencies of conditions linked to ART toxicities among 34,994 adult, ART-naïve patients with specimens referred to the RETRO-CI laboratory in Abidjan, Côte d'Ivoire between 1998 and 2017. Screening included tests for serum creatinine, alanine aminotransferase (ALT) and haemoglobin (Hb) to identify renal dysfunction (estimated glomerular filtration rate < 50 mL/min), hepatic abnormalities (ALT > 5× upper limit of normal) and severe anaemia (Hb < 6.5 g/dL), respectively. We considered screening results across four eras and identified factors associated with the conditions in question., Results: The prevalence of renal dysfunction, hepatic abnormalities and severe anaemia were largely unchanged over time and just 8.4% of patients had any of the three conditions. Key factors associated with renal dysfunction and severe anaemia were age > 50 years (adjusted odds ratio (aOR): 2.53; 95% confidence interval (CI): 2.19-2.92; P < 0.001) and CD4 < 100 cells/µl (aOR: 2.57; 95% CI: 2.30-2.88; P < 0.001)., Conclusion: The relative infrequency of conditions linked to toxicity in Côte d'Ivoire supports the notion that simplification of pre-ART laboratory screening may be undertaken with limited negative impact on identification of adverse events. Targeted screening may be a feasible strategy to balance detection of conditions associated with ART toxicities with simplification of services., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Objectives: Ethiopia's HIV prevalence has decreased by 75% in the past 20 years with the implementation of antiretroviral therapy, but HIV transmission continues in high-risk clusters. Identifying the spatial and temporal trends, and epidemiologic correlates, of these clusters can lead to targeted interventions., Methods: We used biomarker and survey data from the 2005, 2011 and 2016 Ethiopia Demographic and Health Surveys (DHS). The spatial-temporal distribution of HIV was estimated using the Kulldorff spatial scan statistic, a likelihood-based method for determining clustering. Significant clusters (P < 0.05) were identified and compared based on HIV risk factors to non-cluster areas., Results: In 2005, 2011 and 2016, respectively, 219, 568 and 408 individuals tested positive for HIV. Four HIV clusters were identified, representing 17% of the total population and 43% of all HIV cases. The clusters were centred around Addis Ababa (1), Afar (2), Dire Dawa (3) and Gambella (4). Cluster 1 had higher rates of unsafe injections (4.9% vs. 2.2%, P < 0.001) and transactional sex (6.0% vs. 1.6%, P < 0.001) than non-cluster regions, but more male circumcision (98.5% vs. 91.3%, P < 0.001). Cluster 2 had higher levels of transactional sex (4.9% vs. 1.6%, P < 0.01), but lower levels of unsafe injections (0.8% vs. 2.2%, P < 0.01). Cluster 3 had fewer individuals with> 1 sexual partner (0% vs. 1.7%, P < 0.001) and more male circumcision (100% vs. 91.3%, P < 0.001). Cluster 4 had less male circumcision (59.1% vs. 91.3%, P < 0.01)., Conclusions: In Ethiopia, geographic HIV clusters are driven by different risk factors. Decreasing the HIV burden requires targeted interventions., (© 2019 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objectives: HIV-positive men who have sex with men (MSM) with CD4 cell counts> 350 cells/mm 3 in China recently became eligible for free antiretroviral therapy (ART) due to updated national guidelines. This study aimed to investigate ART coverage and adherence among a large sample of HIV-positive MSM in China., Methods: A cross-sectional survey was conducted in Chengdu and Hangzhou, China, from February to November 2016. Participants were 277 MSM who had received a confirmatory HIV diagnosis and had CD4 levels of> 350 cells/mm 3 . Trained staff of collaborating non-governmental organizations contacted all HIV-positive MSM listed in their service records and invited them to join the study. The ART initiation, ART adherence and interactions between healthcare professionals and the patients were assessed., Results: ART coverage was 60.3%. Among those who were on ART (n = 167), no participants reported missing any doses in the last four days, but 25.7% reported non-compliance to either ART dosing schedule or dosage instructions. After adjusting for background variables and perceived eligibility for ART, two variables were significant factors of higher ART coverage: (i) receiving a recommendation from healthcare professionals for immediate ART initiation and (ii) perceiving having received an adequate explanation of potential harms of ART. Being prescribed> 3 pills per dose and not having a temporary resident permit were associated with non-compliance., Conclusions: Significant efforts are needed to increase ART coverage among HIV-positive MSM with high CD4 counts in China. Although prevalence of missing doses was low, non-compliance to dosing schedule/instructions should not be neglected. Interactions between healthcare professionals and MSMs play an important role in facilitating ART initiation., (© 2019 John Wiley & Sons Ltd.)

Objective: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are prevalent in West Africa. To address the WHO 2030 goals of a 90% reduction in incidence and a 65% reduction in mortality for both infections, we assessed the prevalence of HBV and HCV from surveys in the general population., Methods: Participants in this cross-sectional survey were included from randomly selected houses in a demographic surveillance site in Bissau, Guinea-Bissau. Participants were interviewed and had a blood sample drawn for viral analyses (HBsAg, anti-HBs, anti-HBc, anti-HCV and HCV RNA). Risk factors of HBV and HCV infection were determined by binomial regression adjusted for sex and age., Results: A total of 2715 participants were included in this study. The overall HBsAg prevalence was 18.7% (95% CI: 17.3-20.2%). HBsAg was associated with male sex (adjusted risk ratio (aRR): 1.64), and prevalence decreased with age >34 years. HBV exposure was found in 91.9% of participants. Although 72.6% of individuals without sexual debut had been exposed to HBV, ever engaging in a sexual relationship was associated with higher risk of HBV exposure (aRR 1.18). The anti-HCV prevalence was 0.5% (95% CI: 0.3-0.9%), and 78.6% of those had detectable HCV RNA. Risk factors for anti-HCV sero-positivity were age above 55 (aRR 10.60), a history of blood transfusion (aRR 5.07) and being in a polygamous marriage (aRR 3.52)., Conclusion: In Guinea-Bissau initiatives to implement treatment and widespread testing are needed to reach the WHO 2030 goals., (© 2019 John Wiley & Sons Ltd.)

Objective: Highly active antiretroviral therapy (HAART) has considerably reduced HIV/AIDS-related morbidity and mortality; however, the therapy has been associated with the development of cardiovascular disease (CVD), and genetic predisposition factors may aggravate disease outcome. This study was aimed at investigating the relationship between haptoglobin phenotypes and risk factors of CVD in HIV patients., Methods: A total of 105 HIV sero-positive patients on HAART and 75 HIV-infected HAART-naïve individuals were enrolled in the study. Socio-demographics and clinical characteristics of the participants were obtained using a well-structured questionnaire. Lipid profile, lactate dehydrogenase (LDH) and haptoglobin (Hp) phenotypes were analysed from serum whiles haemoglobin (Hb) level, CD4 + cell count and HIV viral RNA load were determined using whole blood., Results: Atherogenic index of plasma (AIP) was significantly higher in patients on HAART than the naïve group (P < 0.05). Age, BMI, visceral fat, systolic blood pressure LDH and lipid variables strongly and positively correlated with AIP (P < 0.05), with the exception of HDL-c (P < 0.001) which showed a negative correlation. HAART was associated with hypertension (χ 2  = 4.33, P = 0.037), hypercholesterolaemia (χ 2  = 10.99, P < 0.001), elevated LDL-c (χ 2 = 10.30, P < 0.001) and decreased HDL-c (χ 2  = 3.87, P = 0.09). Hp2-2 and Hp0 collectively was strongly associated with hypertension (OR = 2.54, P = 0.011), obesity (OR = 5.97, P < 0.001) and hypercholesterolaemia (OR = 2.99, P < 0.001)., Conclusion: HIV/AIDS patients on HAART expressing Hp phenotypes with weak antioxidant capacity have an increased risk of developing CVD., (© 2019 John Wiley & Sons Ltd.)

Objective: To assess the association between timing of maternal combination ART (cART) initiation and stillbirth among HIV-infected pregnant women in Malawi's Option B+ programme., Methods: Cohort study of HIV-infected pregnant women delivering singleton live or stillborn babies at ≥28 weeks of gestation using routine data from maternity registers between 1 January 2012 and 30 June 2015. We defined stillbirth as death of a foetus at ≥28 weeks of gestation. We report proportions of stillbirth according to timing of maternal cART initiation (before pregnancy, 1st or 2nd trimester, or 3rd trimester or labour). We used logistic regression, with robust standard errors to account for clustering of women within health facilities, to investigate the association between timing of cART initiation and stillbirth., Results: Of 10 558 mother-infant pairs abstracted from registers, 8380 (79.4%) met inclusion criteria. The overall rate of stillbirth was 25 per 1000 deliveries (95% confidence interval 22-29). We found no significant association between timing of maternal cART initiation and stillbirth. In multivariable models, older maternal age, male sex of the infant, breech vaginal delivery, delivery at < 34 weeks of gestation and experience of any maternal obstetric complication were associated with higher odds of stillbirth. Deliveries managed by a mission hospital or health centre were associated with lower odds of stillbirth., Conclusion: Pregnant women's exposure to cART, regardless of time of its initiation, was not associated with increased odds of stillbirth., (© 2019 John Wiley & Sons Ltd.)

Objective: To describe growth evolution and its correlates in the first 5 years of antiretroviral therapy (ART) initiation among HIV-infected children followed up in West Africa., Methods: All HIV-infected children younger than 10 years followed in the IeDEA pWADA cohort while initiating ART, with at least one anthropometric measurement within the first 5 years of treatment were included in the study. Growth was described according to the WHO child growth standards, using Weight-for-age Z-score (WAZ), Height-for-age Z-score (HAZ) and Weight-for-Height/BMI-for-age Z-score (WHZ/BAZ). Growth evolution and its correlates, measured at ART initiation, were modelled in individual linear mixed models for each anthropometric indicator, with a spline term added at the 12-, 24- and 9-month time point for WAZ, HAZ and WHZ/BAZ, respectively., Results: Among the 4156 children selected (45% girls, median age at ART initiation 3.9 years [IQR interquartile range 1.9-6.6], and overall 68% malnourished at ART initiation), important gains were observed in the first 12, 24 and 9 months on ART for WAZ, HAZ and WHZ/BAZ, respectively. Correlates at ART initiation of a better growth evolution overtime were early age (<2 years of age), severe immunodeficiency for age, and severity of malnutrition., Conclusions: Growth evolution is particularly strong within the first 2 years on ART but slows down after this period. Weight and height gains help to recover from pre-ART growth deficiency but are insufficient for the most severely malnourished. The first year on ART could be the best period for nutritional interventions to optimize growth among HIV-infected children in the long-term., (© 2019 John Wiley & Sons Ltd.)

Objective: Caregiver socio-emotional attributes are major determinants of child well-being. This investigation in vulnerable school-aged Ugandan children estimates relationships between children's well-being and their caregiver's anxiety, depression and social support., Methods: Perinatally HIV-infected, HIV-exposed uninfected and HIV-unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNA-polymerase chain-reaction test; status was confirmed via HIV rapid diagnostic test when children were 6-18 years old. Five indicators of child well-being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregivers' socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (β) and corresponding 95% confidence intervals (CI) for child well-being in relation to caregiver's psychosocial status., Results: As per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower self-esteem/QOL (β = -1.3%/-2.6%; 95%CI: -5.0%,-0.2%) in their children. Child distress/hopelessness increased (β = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and self-esteem/QOL decreased 2.3% (β = -2.3%/-4.4%; 95%CI: -7.2%, -1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (β = 3%; 95%CI:1.4%, 4.5%) in their children. HIV-infected/exposed children had most caregiver depression-related QOL deficit (β = -5.2%/-6.8%; 95%CI: -12.4%, -0.2%) and HIV-unexposed children had most caregiver social support-related enhancements in positive outlook (β=4.5%; 95%CI:1.9%, 7.1%)., Conclusions: Caregiver anxiety, depressive symptoms and low social support were associated with worse well-being in school-aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving well-being of vulnerable children and adolescents in this setting., (© 2019 John Wiley & Sons Ltd.)

Introduction: There are concerns that immediate ART initiation (regardless of CD4 count) negatively affects HIV status disclosure, ART adherence and healthcare interactions. We assessed changes in these factors after the 'Early access to ART for all' intervention, a universal test-and-treat study in Swaziland., Methods: We recruited two samples of participants between 2014 and 2017. The first group was interviewed before the intervention (control); the second group at the implementation and 6 months thereafter (intervention)., Results: High levels of disclosure to partners (controls and intervention: 94%) and family members (controls: 78%, intervention: 79%) were reported, and high levels of adherence (85% did not miss a dose among the controls, 84% in the intervention group). There were no changes in patients reporting feeling pressured to initiate ART (controls: 10%, intervention: 11%). The quality of interaction with healthcare workers improved after the intervention; healthcare workers explained more often the choice of ART initiation (controls: 88%, intervention: 93%) and the meaning of both CD4 and viral load test results (controls: 15%, intervention: 47%). More patients in the intervention group reported receiving test results (controls: 13%, intervention: 46%). We observed no changes in disclosure, adherence or patient experiences 6 months into the intervention compared to its start., Conclusion: Our results suggest that both reported adherence and disclosure levels remain high after the introduction of immediate ART in Swaziland. We observed an improvement in the healthcare interactions, possibly due to training at participating facilities, which will be an important element for a successful roll-out of immediate ART., (© 2019 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objectives: Restricted capacity for viral load (VL) testing is a major obstacle for antiretroviral therapy (ART) programmes in high-burden regions. Algorithms for targeted VL testing could help allocate laboratory resources rationally. We validated the performance of the Viral Load Testing Criteria (VLTC), an algorithm with satisfactory performance in derivation (sensitivity 91%, specificity 43%)., Methods: HIV-positive adults who had been receiving first-line ART for ≥12 months at three Ethiopian public ART clinics were included. Healthcare providers collected data on variables of the VLTC: current CD4 count, mid-upper arm circumference (MUAC) and self-reported treatment interruption. VL testing was performed in parallel. Performance of the algorithm for identification of patients with VL ≥ 1000 copies/ml was evaluated., Results: Of 562 patients (female 62%, median ART duration 92 months), 33 (6%) had VL ≥ 1000 copies/ml. Sensitivity for the VLTC was 85% (95% CI, 68-95), specificity 60% (95% CI, 55-64), positive predictive value 12% (95% CI, 10-14) and negative predictive value 98% (95% CI, 97-99). Use of the algorithm would reduce the number of VL tests required by 57%. Misclassification occurred in 5/33 (15%) of subjects with VL ≥ 1000 copies/ml., Conclusion: In validation, the VLTC performed similarly well as derivation. Use of the VLTC may be considered for targeted VL testing for ART monitoring in high-burden regions., (© 2019 John Wiley & Sons Ltd.)

Objectives: A growing evidence base implicates human cytomegalovirus (HCMV) as a risk factor for TB disease. We investigated total IgG and mycobacteria-specific antibodies in a cross-sectional study nested within a rural Ugandan General Population Cohort (GPC), in relation to HIV infection and the magnitude of HCMV IgG response., Methods: Sera from 2189 individuals (including 27 sputum-positive TB cases) were analysed for antibodies against mycobacteria (Ag85A, PPD, LAM, ESAT6/CFP10) and HCMV, tetanus toxoid (TT) and total IgG., Results: Anti-mycobacterial antibodies increased with age until approximately 20 years, when they plateaued. Higher HCMV exposure (measured by IgG) was associated with lower levels of some anti-mycobacterial antibodies, but no increase in total IgG. HIV infection was associated with a decrease in all anti-mycobacterial antibodies measured and with an increase in total IgG., Conclusions: The increase in anti-mycobacterial antibodies with age suggests increasing exposure to non-tuberculous mycobacteria (NTM), and to M.tb itself. HIV infection is associated with decreased levels of all mycobacterial antibodies studied here, and high levels of HCMV IgG are associated with decreased levels of some mycobacterial antibodies. These findings point towards the importance of humoral immune responses in HIV/TB co-infection and highlight a possible role of HCMV as a risk factor for TB disease., (© 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objectives: Cervical cancer screening by visual inspection with acetic acid (VIA) is a widely used alternative to cytology in developing countries. This study aimed to evaluate risk factors associated with a positive VIA test and with cervical high-grade lesions on cytology., Methods: We conducted a large cross-sectional study among 3339 women from urban and rural Tanzania. Study participants were interviewed about socio-demographic, reproductive and lifestyle factors. Blood samples were tested for HIV, and a gynaecological examination was performed. Human papillomavirus (HPV) status was determined by Hybrid Capture 2, and HPV genotyping was done using the LiPA Extra test. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and confidence intervals (CIs)., Results: The strongest risk factors for VIA positivity were positivity to HIV (OR = 3.48; 95% CI: 2.34-5.17) or to high-risk HPV (HrHPV) (OR = 1.97; 95% CI: 1.37-2.85). HrHPV was by far the strongest predictor of high-grade cytology (OR = 110.1; 95% CI: 50.4-240.4), while there was no significant association with HIV in the multivariable analysis (OR = 1.27; 95% CI: 0.78-2.08). After adjustment for HrHPV, HIV and age, the risk of high-grade cytology also increased with increasing age, number of births and low body mass index (BMI), while high BMI decreased the risk of VIA positivity., Conclusions: Infection with HrHPV is a major risk factor for high-grade cytology, while VIA positivity is associated with HIV and to a lesser extent with HrHPV., (© 2018 John Wiley & Sons Ltd.)

Objective: To measure linkage to care and antiretroviral therapy (ART) initiation among newly diagnosed individuals with HIV in a rural Tanzanian community., Methods: We included all new HIV diagnoses of adults made between 2014 and 2017 during community- or facility-based HIV testing and counselling (HTC) in a rural ward in northwest Tanzania. Community-based HTC included population-level HIV serological testing (sero-survey), and facility-based HTC included a stationary, voluntary HTC clinic (VCT) and an antenatal clinic (ANC) offering provider-initiated HTC (ANC-PITC). Cox regression models were used to compare linkage to care rates by testing modality and identify associated factors. Among those in care, we compared initial CD4 cell counts and ART initiation rates by testing modality., Results: A total of 411 adults were newly diagnosed, of whom 10% (27/265 sero-survey), 18% (3/14 facility-based ANC-PITC) and 53% (68/129 facility-based VCT) linked to care within 90 days. Individuals diagnosed using facility-based VCT were seven times (95% CI: 4.5-11.0) more likely to link to care than those diagnosed in the sero-survey. We found no difference in linkage rates between those diagnosed using facility-based ANC-PITC and sero-survey (P = 0.26). Among individuals in care, 63% of those in the sero-survey had an initial CD4 count >350 cells/mm 3 vs. 29% of those using facility-based VCT (P = 0.02). The proportion who initiated ART within 1 year of linkage to care was similar for both groups (94% sero-survey vs. 85% facility-based VCT; P = 0.16)., Conclusions: Community-based sero-surveys are important for earlier diagnosis of HIV-positive individuals; however, interventions are essential to facilitate linkage to care., (© 2018 The Authors. Tropical Medicine & International Health published by John Wiley & Sons Ltd.)

Objective: To evaluate how electronic data management systems affect data use practices in antiretroviral therapy (ART) programs within local health districts, and individual health facilities., Methods: We used a data quality audit to establish a baseline of the quality of data in the electronic register alongside in-depth interviews with health workers and managers, to understand perceptions of data quality, data use by facility staff and challenges affecting data use., Results: The findings provide a four-level continuum of data use that can be applied to other settings and recommendations for optimising facility-level data use., Conclusion: By defining four levels of data use our findings suggest the potential to encourage a structured process of moving from passive data use, to more active and engaged data use, where data could be used to anticipate patient behaviour and link that behaviour to differentiated care plans., (© 2018 John Wiley & Sons Ltd.)

Objectives: To estimate the magnitude of mortality and loss to follow-up and describe predictors of mortality among HIV-infected children in Guinea-Bissau., Methods: Retrospective follow-up study among HIV-infected children under 15 years of age at the largest HIV-clinic in Guinea-Bissau from 2006-2016. A multivariate Cox proportional hazards model was used to identify predictors of mortality., Results: Of 525 children were included in the analysis: 371 (70.7%) with HIV-1, 17 (3.2%) with HIV-2, 25 (4.8%) with HIV-1/2, and 112 (21.3%) with HIV of unknown type. At diagnosis, the median age was 3.5 years, 44.7% met the WHO criteria for severe immunodeficiency by age based on CD4 cell count, and 59.4% were underweight. The median follow-up time was 6 months. Despite the availability of antiretroviral treatment, the mortality rate was 10.4 deaths per 100 person-years of follow-up. Within the first year of follow-up, 11.0% died, 3.1% were transferred and 38.8% were lost to follow-up, leaving 47.1% in follow-up. Severe immunodeficiency (adjusted hazard ratio (aHR) = 2.52, 95% CI: 1.22-5.21) and underweight (aHR = 3.14, 95% CI: 1.40-7.02) were independent predictors of mortality., Conclusions: This study reveals a high rate of early mortality and loss to follow-up among HIV-infected children in Guinea-Bissau. Initiatives to improve patient retention are urgently needed., (© 2018 John Wiley & Sons Ltd.)

Objectives: To evaluate a paediatric treatment-support intervention for home-based treatment of HIV infection or tuberculous meningitis (TBM)., Methods: A randomised-controlled study comparing local standard care (controls) with standard care plus intervention (combining adherence education, reinforcement and monitoring) in children aged 0-14 years. We recorded adherence measures (self-report, pill-count, drug-assays for isoniazid and rifampicin in urine and pyrazinamide in saliva), difficulties administering medication and PedsQL™questionnaires for health-related quality-of-life (HRQoL) and family impact., Results: In the HIV group (6-months follow-up, n = 195), more children had above-median HRQoL-scores in the intervention group than in the control group (P = 0.009). Problems reported administering medication declined between baseline and follow-up for controls (P = 0.043). Disclosure of HIV status to the child increased between baseline and follow-up in both groups (intervention P < 0.001; control P = 0.031). In the TBM group (3-months follow-up, n = 43), all adherence measures remained high for both intervention and controls, except for rifampicin which declined between baseline and follow-up in the intervention group (P = 0.031). The intervention group maintained above median HRQoL-scores between baseline and follow-up, when the number of children with above-median HRQoL-scores decreased in the controls (P = 0.063). More children in the intervention group had above-median family impact-scores than controls (P = 0.040)., Conclusions: The low-cost, culturally friendly treatment-support intervention had beneficial effects on health-related quality of life, family impact, caregiver disclosure of HIV status to the child, increased caregiver reporting of medication non-adherence and caregiver reporting of difficulties administering medication. Treatment adherence was not significantly affected in either HIV or TBM group., (© 2018 John Wiley & Sons Ltd.)

Objectives: To assess the costs and cost-effectiveness of transitioning from antiretroviral therapy (ART) initiation based on CD4 cell count and WHO clinical staging ('Option A') to universal ART ('Option B+') for all HIV-infected pregnant and breastfeeding women in Swaziland., Methods: We measured the total costs of prevention of mother-to-child HIV transmission (PMTCT) service delivery at public sector facilities with empirical cost data collected at three points in time: once under Option A and again twice after transition to the Option B+ approach. The cost per woman treated per month includes recurrent costs (personnel, overheads, medication and diagnostic tests) and capital costs (buildings, furniture, start-up costs and training). Cost-effectiveness was estimated from the health services perspective as the cost per woman retained in care through 6 months postpartum. This analysis is nested within a larger stepped-wedge evaluation, which demonstrated a 26% increase in maternal retention after the transition to Option B+., Results: Across the five sites, the total cost for PMTCT during the study period (from August 2013 to October 2015, in 2015 US$) was $868,426 for Option B+ and $680 508 for Option A. The cost per woman treated per month was $183 for a woman on ART under Option B+, and $127 and $118 for a woman on ART and zidovudine (AZT), respectively, under Option A. The weighted average cost per woman treated on Option B+ was $826 compared to $525 under Option A. The main cost drivers were the start-up costs, additional training provided and staff time spent on PMTCT tasks for Option B+. The incremental cost-effectiveness ratio was estimated at $912 for every additional mother retained in care through six months postpartum., Conclusions: The cost and cost-effectiveness outcomes from this study indicate that there is a robust economic case for pursuing the Option B+ approach in Swaziland and similar settings such as South Africa. Furthermore, these costs can be used to aid decision making and budgeting, for similar settings transitioning to test and treat strategy., (© 2018 John Wiley & Sons Ltd.)

Objectives: To describe the prevalence of CMV in a cohort of HIV infected individuals in Guinea-Bissau, West Africa and to evaluate differences in patients' clinical characteristics associated with their CMV status., Methods: Newly diagnosed HIV infected adults were invited to participate in this cross-sectional study, from May until December 2015. Enrolled patients were interviewed and underwent a full physical examination focusing on CMV disease manifestations. Blood samples were analysed for CMV serology, QuantiFERON-CMV response and CMV DNA. Mortality follow-up were registered for one year after inclusion., Results: In total, 180 patients were enrolled. Anti-CMV IgG positivity was found in 100% (138/138) and 2.8% (4/138) were anti-CMV IgM positive. A positive QuantiFERON-CMV response was found in 85.7% (60/70) of the patients and 60.6% (83/137) had CMV viraemia. QuantiFERON-CMV response and detectable CMV DNA were associated with lower CD4 cell count, older age and upper gastrointestinal complaints. During one year of follow-up, the IRR for death among CMV DNA positive patients was 1.5 (P = 0.5)., Conclusions: CMV coinfection was detected among all enrolled patients and CMV viraemia was highly prevalent. Only age and upper gastrointestinal complaints were associated with the patients' CMV status., (© 2018 John Wiley & Sons Ltd.)

Objective: To evaluate mother and infant outcomes in the largest prevention of mother-to-child-transmission (PMTCT) programme in Haiti in order to identify gaps towards elimination of HIV and syphilis., Methods: Based on retrospective data from HIV+ pregnant women and their infants enrolled in PMTCT care from 1999 to 2014, we assessed maternal enrolment in PMTCT, receipt of antiretrovirals before delivery, maternal retention through delivery as well as infant enrolment in PMTCT, HIV testing and HIV infection. Four PMTCT programme periods were compared: period 1 (1999-2004, mono ARV), period 2 (2005-2009, dual ARV), period 3 (2010-2012, Option B) and period 4 (Oct 2012-2014, Option B+). Kaplan-Meier methods were used to assess retention in PMTCT care., Results: Among 4665 pregnancies, median age was 27 years and median CD4+ was 494 cells/μl (IQR 328-691). A total of 75% of women received antiretrovirals before delivery, and 73% were retained in care through delivery. Twenty-two percent of women were lost before delivery, <1% died and 6% had stillbirths or abortions. Ninety-four percent of infants who were born alive enrolled in PMTCT, of whom 92% had complete HIV testing. One hundred and sixty-one infants were HIV+, giving a 5.4% HIV transmission rate (9.8%, 4.6%, 5.8% and 3.6% in periods 1-4). Retention among women through 12 months after PMTCT enrolment did not significantly differ across periods. However, among women who received antiretrovirals at the time of enrolment, retention 12 months later was lower in the Option B+ period (83%) than in periods 2 and 3 (94% and 93%) (P < 0.001). Syphilis infection among women decreased from 16% in period 1 to 8% in period 4, whereas syphilis testing of infants increased from 17% to 91%., Conclusion: Despite dramatic reductions in MTCT in Haiti, interventions are needed to improve retention to achieve MTCT elimination of HIV and syphilis., (© 2018 John Wiley & Sons Ltd.)

Objective: To determine the prevalence of and risk factors for metabolic syndrome (MS) in HIV-infected adults at three urban clinics in Bukavu, Democratic Republic of the Congo., Design: Cross-sectional study., Methods: From July to September 2016, baseline socio-demographics, risk factors and clinical characteristics were collected using a structured questionnaire or extracted from medical records. Fasting blood sugar and lipids were measured. MS was defined per the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) criteria. Adjusted odds ratio (OR) was generated through multivariate logistic regression models., Results: Of 495 participants, 356 (72%) were women and 474 (95.8%) were receiving antiretroviral therapy (ART). The median age (years) [interquartile range (IQR)] was 43 [36-51]. The overall prevalence of MS per NECP/ATP III and IDF criteria was 27% [95% CI: 20-35%] or 30% [95% CI: 23-38%], respectively. In a multivariate logistic regression, low physical activity (OR 2.47, 95% CI: 1.40-4.36); daily exposure to biomass fuel smoke (BMF) for more than 2 h (OR 2.18, 95% CI: 1.01-4.68); protease inhibitor containing ART (OR: 2.96, 95% CI: 1.07-8.18); and stavudine-containing ART regimen (OR: 2.57, 95% CI: 1.11-5.93) were independently associated with MS., Conclusions: MS was highly prevalent in this hospital-based study population. Beside known traditional risk factors and contribution of specific ART regimens to MS, daily exposure to BMF is new and of specific concern, necessitating targeted urgent prevention and management interventions., (© 2018 John Wiley & Sons Ltd.)

Introduction: Human immunodeficiency virus (HIV)-infected individuals are at increased risk for all forms of extrapulmonary tuberculosis (TB), including tuberculous meningitis (TBM). This study aimed to investigate the frequency of HIV in patients with TBM., Methods: PubMed, Embase, Web of Science and Cochrane Library were searched for articles including relevant data. Stata version 14.0 (StataCorp, College Station, Texas, USA) was used to analyse the data., Results: Twenty studies were identified. The pooled frequency of HIV among adult patients with TBM was 38.0% (95% CI: 21.0-57.0; I 2 = 97%). In children (under the age of 15 years), 6.0% (95% CI: 1.0-13.0; I 2 = 0.0%) had HIV infection. In patients with bacterial meningitis other than TBM, 36.0% (95% CI: 19.0-53.0; I 2 = 100%) were HIV-infected., Conclusions: A relatively high frequency of HIV in patients with TBM was indicated by our study. Establishment of diagnostic criteria and effective treatment strategies for TBM/HIV co-infection are recommended for better management of patients with TBM+HIV., (© 2018 John Wiley & Sons Ltd.)

Objectives: WHO recommends HIV viral load (VL) testing 6 months after antiretroviral therapy (ART) initiation and every 12 months thereafter, but cost prohibits routine, universal VL testing in many developing countries. We sought to devise a targeted approach to routine VL monitoring that could reduce cost and identify those at low risk for virologic failure (VF)., Methods: We analysed screening data from a clinical trial enrolling adults on ART in Malawi. We identified risk factors associated with VF and employed the Knill-Jones method to assign summary score identifying persons at lower risk for VF., Results: Among 957 adults, prevalence of VF was 9.4%. Factors independently associated with VF included age <38 years (OR 3.44, 95% CI 2.01-5.89), ART duration >2.5 years (OR 2.98, 95% CI 1.79-4.96), ART adherence <95% (OR 1.76, 95% CI 1.06-2.94), CD4 count <200 cells/μl (OR 5.94, 95% CI 3.27-10.78), haemoglobin <13 g/dl (OR 2.76, 95% CI 1.70-4.50) and CD8 count >885 cells/μl (OR 2.10, 95% CI 1.28-3.44). Our VF prediction summary score included all factors above except CD8 count and was fairly accurate with validated area under receiver operating characteristic curve of 0.76. Implementation could reduce VL testing by 65%., Conclusion: A simple score incorporating age, ART duration and adherence, and CD4 count can accurately identify adults at low risk for VF in a sub-Saharan African setting. In areas with high ART utilisation and limited VL testing capacity, a targeted approach could optimise routine VL monitoring while identifying adults in need of alternate ART regimens., (© 2018 John Wiley & Sons Ltd.)

Objective: To describe the associations between socio-economic position and prevalent tuberculosis in the 2010 ZAMSTAR Tuberculosis Prevalence Survey, one of the first large tuberculosis prevalence surveys in Southern Africa in the HIV era., Methods: The main analyses used data on 34 446 individuals in Zambia and 30 017 individuals in South Africa with evaluable tuberculosis culture results. Logistic regression was used to estimate adjusted odds ratios for prevalent TB by two measures of socio-economic position: household wealth, derived from data on assets using principal components analysis, and individual educational attainment. Mediation analysis was used to evaluate potential mechanisms for the observed social gradients., Results: The quartile with highest household wealth index in Zambia and South Africa had, respectively, 0.55 (95% CI 0.33-0.92) times and 0.70 (95% CI 0.54-0.93) times the adjusted odds of prevalent TB of the bottom quartile. College or university-educated individuals in Zambia and South Africa had, respectively, 0.25 (95% CI 0.12-0.54) and 0.42 (95% CI 0.25-0.70) times the adjusted odds of prevalent TB of individuals who had received only primary education. We found little evidence that these associations were mediated via several key proximal risk factors for TB, including HIV status., Conclusion: These data suggest that social determinants of TB remain important even in the context of generalised HIV epidemics., (© 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objectives: To assess adherence outcomes to antiretroviral therapy (ART) of recipients ≥50 years in Soweto, South Africa., Methods: This was a secondary data analysis for a cross-sectional study at two HIV clinics in Soweto. Data on ART adherence and covariates were gathered through structured interviews with HIV 878 persons living with HIV (PLHIV) receiving ART. Logistic regression analysis was used to assess associations., Results: PLHIV ≥50 years (n = 103) were more likely to miss clinic visits during the last six months than PLHIV aged 25-49 (OR 2.15; 95%CI 1.10-4.18). PLHIV ≥50 years with no or primary-level education were less likely to have missed a clinic visit during the last six months than PLHIV with secondary- or tertiary-level education in the same age category (OR 0.3; 95%CI 0.1-1.1), as were PLHIV who did not disclose their status (OR 0.2; 95%CI 0-1.1). There was no evidence of increased risk for non-adherence to ART pills and drug refill visits among older PLHIV., Conclusion: Missing a clinic visit was more common among older PLHIV who were more financially vulnerable. Further studies are needed to verify these findings and identify new risk factors associated with ART adherence., (© 2017 John Wiley & Sons Ltd.)

Introduction: Decreasing international financial resources for HIV and increasing numbers of antiretroviral treatment (ART)-treated patients may jeopardise treatment continuity in low-income settings. Using data from the EVOLCam ANRS-12288 survey, this study aimed to document the prevalence of unplanned treatment interruption for more than 2 consecutive days (TI>2d) and investigate the associated individual and health care supply-related factors within the Cameroonian ART programme., Methods: A cross-sectional mixed methods survey was carried out between April and December 2014 in 19 HIV services of the Centre and Littoral regions. A multilevel logistic model was estimated on 1885 ART-treated patients in these services to investigate factors of TI>2d in the past 4 weeks., Results: Among the study population, 403 (21%) patients reported TI>2d. Patients followed up in hospitals reporting ART stock-outs were more likely to report TI>2d while those followed up in the Littoral region, in medium- or small-sized hospitals and in HIV services proposing financial support were at lower risk of TI>2d. The following individual factors were also associated with a lower risk of TI>2d: living in a couple, having children, satisfaction with attention provided by doctor, tuberculosis co-infection and not having consulted a traditional healer., Conclusions: Besides identifying individual factors of TI>2d, our study highlighted the role of health care supply-related factors in shaping TI in Cameroon's ART programme, especially the deleterious effect of ART stock-outs. Our results also suggest that the high proportion of patients reporting TI could jeopardise progress in the fight against HIV in the country, unless effective measures are quickly implemented like ensuring the continuity of ART supply., (© 2018 John Wiley & Sons Ltd.)

Objective: In Thailand, 7.2% of HIV patients are co-infected with hepatitis C virus (HCV), and these patients are treated with peg-interferon + ribavirin (PR) for their HCV infection. This study evaluates efficacy and safety of PR treatment and pharmacokinetics of ribavirin in this population., Methods: HIV/HCV co-infected Thai patients were treated with PR for 24 or 48 weeks. Sustained virological response 24 weeks after the end of treatment (SVR24) was used to describe efficacy. (laboratory) safety parameters and ribavirin plasma concentrations were evaluated during study visits. Ribavirin concentrations were compared with t-tests for patients with and without anaemia (haemoglobin <10 g/dl) and SVR24., Results: A total of 101 HIV/HCV co-infected patients were included; 88% were male (n = 88), and 46% were infected with genotype 3. The median (IQR) start dose was 14.28 mg/kg/day. SVR24 rate was 56%. All patients reported at least one (serious) adverse event, of which 28% of patients developed anaemia. Seven patients discontinued treatment due to toxicity issues. Geometric mean (IQR) ribavirin concentration was 1.81 (1.42-2.32) mg/l at week 8 of treatment. At week 8, patients with and without anaemia and SVR had ribavirin concentrations of 2.29 and 1.63 mg/l and 1.91 and 1.74 mg/l, respectively., Conclusions: PR treatment has comparable response rates and toxicity profile in Thai HIV/HCV co-infected patients as in Western HIV/HCV patients. However, ribavirin plasma concentrations were comparable with previously published studies in HIV/HCV co-infected patients, but both, just as SVR rate, were lower than in mono-infected patients., (© 2017 John Wiley & Sons Ltd.)

Objective: International guidelines recommend countries to expand antiretroviral therapy (ART) to all HIV-infected individuals and establish local-level priorities in relation to other treatment, prevention and mitigation interventions through fair processes. However, no practical guidance is provided for such priority-setting processes. Evidence-informed deliberative processes (EDPs) fill this gap and combine stakeholder deliberation to incorporate relevant social values with rational decision-making informed by evidence on these values. This study reports on the first-time implementation and evaluation of an EDP in HIV control, organised to support the AIDS Commission in West Java province, Indonesia, in the development of its strategic plan for 2014-2018., Methods: Under the responsibility of the provincial AIDS Commission, an EDP was implemented to select priority interventions using six steps: (i) situational analysis; (ii) formation of a multistakeholder Consultation Panel; (iii) selection of criteria; (iv) identification and assessment of interventions' performance; (v) deliberation; and (vi) selection of funding and implementing institutions. An independent researcher conducted in-depth interviews (n = 21) with panel members to evaluate the process., Results: The Consultation Panel included 23 stakeholders. They identified 50 interventions and these were evaluated against four criteria: impact on the epidemic, stigma reduction, cost-effectiveness and universal coverage. After a deliberative discussion, the Consultation Panel prioritised a combination of several treatment, prevention and mitigation interventions., Conclusion: The EDP improved both stakeholder involvement and the evidence base for the strategic planning process. EDPs fill an important gap which international guidelines and current tools for strategic planning in HIV control leave unaddressed., (© 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI)., Methods: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment., Results: Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models., Conclusion: High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB., (© 2017 John Wiley & Sons Ltd.)

Objective: Increasing numbers of children with HIV are surviving to adolescence and encountering multiple clinical and social consequences of long-standing HIV infection. We aimed to investigate the association between HIV and disability, social functioning and school inclusion among 6- to 16-year-olds in Zimbabwe., Methods: HIV-infected children receiving antiretroviral therapy from a public-sector HIV clinic and HIV-uninfected children attending primary care clinics in the same catchment area were recruited. Standardised questionnaires were used to collect socio-demographic, social functioning and disability data. Multivariable logistic regression was used to assess the relationship between HIV status and disability and functioning., Results: We recruited 202 HIV-infected and 285 HIV-uninfected children. There was no difference in age and gender between the two groups, but a higher proportion of HIV-infected children were orphaned. The prevalence of any disability was higher in HIV-infected than uninfected children (37.6% vs. 18.5%, P < 0.001). HIV-infected children were more likely to report anxiety (adjusted odds ratio (aOR) 4.4; 95% CI 2.4, 8.1), low mood (aOR 4.2; 2.1, 8.4) and difficulty forming friendships (aOR 14.8; 1.9, 116.6) than uninfected children. Children with HIV also reported more missed school days, repeating a school year and social exclusion in class. These associations remained apparent when comparing children with HIV and disability to those with HIV but no disabilities., Conclusions: Children with HIV commonly experience disabilities, and this is associated with social and educational exclusion. Rehabilitation and support services are needed to facilitate educational attainment and social participation in this group., (© 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objectives: To assess the relationship between CD4 count at presentation and ART uptake and assess predictors of timely treatment initiation in rural KwaZulu-Natal, South Africa., Methods: We used Kaplan-Meier and Cox proportional hazards models to assess the association between first CD4 count and time from first CD4 to ART initiation among all adults presenting to the Hlabisa HIV Treatment and Care Programme between August 2011 and December 2012 with treatment-eligible CD4 counts (≤ 350 cells/mm 3 ). For a subset of healthier patients (200 < CD4 ≤ 350 cells) residing within the population surveillance of the Africa Health Research Institute, we assessed sociodemographic, economic and geographic predictors hypothesised to influence ART uptake., Results: A total of 4739 patients presented for care with eligible CD4 counts. The proportion initiating ART within six months of diagnosis was 67% (95% CI 63, 71) in patients with CD4 ≤ 50, 59% (0.55, 0.63) in patients with CD4 151-200 and 48% (95% CI 44, 51) in patients with CD4 301-350. The hazard of starting ART fell by 17% (95% CI 14, 20) for every 100-cell increase in baseline CD4 count. Among healthier patients under demographic surveillance (n = 193), observable sociodemographic, economic and geographic predictors did not add discriminatory power beyond CD4 count, age and sex to identify patients at high risk of non-initiation., Conclusions: Individuals presenting for HIV care at higher CD4 counts were less likely to initiate ART than patients presenting at low CD4 counts. Overall, ART uptake was low. Under new guidelines that establish ART eligibility regardless of CD4 count, patients with high CD4 counts may require additional interventions to encourage treatment initiation., (© 2017 John Wiley & Sons Ltd.)

Objectives: To explore the relationship between Efavirenz (EFV) and neuropsychiatric symptoms among adults and adolescents living with human immunodeficiency virus (HIV) in Kilimanjaro, Tanzania., Methods: Cross-sectional study among HIV-infected adults (age 18-65) and adolescents (age 12-17) on antiretroviral treatment attending Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Neuropsychiatric symptoms were measured using the Hospital Anxiety and Depression Scale (HADS), the Symptom Checklist 90 (SCL-90) and the Mini-International Neuropsychiatric Interview (MINI). manova and chi-squared tests were used to test differences between EFV and non-EFV-treated participants., Results: A total of 215 adults and 150 adolescents participated. About 52% of adults and 37% of adolescents used EFV. Among adults, depression scores were higher for those on EFV (HADS (Cohen's D: 0.38; P = 0.02) and SCL-90 (Cohen's D: 0.24; P = 0.03). Among adolescents, those on EFV had lower scores on depression (HADS (Cohen's D: 0.3; P = 0.02) and SCL-90 (Cohen's D: 0.1; P = 0.02). About 10% of adults reported suicidal thoughts, but there was no difference between those on EFV and those without. Lastly, adults on EFV reported higher levels of problematic alcohol use (P = 0.003)., Conclusions: In line with the previous studies, EFV is associated with depressive symptoms and problematic alcohol use among HIV-infected adults in Tanzania. In contrast, EFV was associated with lower levels of depressive symptoms in adolescents in Tanzania. Particularly among adults, close monitoring of depressive symptoms and alcohol use is indicated., (© 2017 John Wiley & Sons Ltd.)

Objectives: Despite the success of Prevention of Mother-to-Child Transmission of HIV (PMTCT) programmes, low uptake of services and poor retention pose a formidable challenge to achieving the elimination of vertical HIV transmission in low- and middle-income countries. This systematic review summarises interventions that demonstrate statistically significant improvements in service uptake and retention of HIV-positive pregnant and breastfeeding women and their infants along the PMTCT cascade., Methods: Databases were systematically searched for peer-reviewed studies. Outcomes of interest included uptake of services, such as antiretroviral therapy (ART) such as initiation, early infant diagnostic testing, and retention of HIV-positive pregnant and breastfeeding women and their infants. Interventions that led to statistically significant outcomes were included and mapped to the PMTCT cascade. An eight-item assessment tool assessed study rigour., Prospero Id: CRD42017063816., Results: Of 686 citations reviewed, 11 articles met inclusion criteria. Ten studies detailed maternal outcomes and seven studies detailed infant outcomes in PMTCT programmes. Interventions to increase access to antenatal care (ANC) and ART services (n = 4) and those using lay cadres (n = 3) were most common. Other interventions included quality improvement (n = 2), mHealth (n = 1), and counselling (n = 1). One study described interventions in an Option B+ programme. Limitations included lack of HIV testing and counselling and viral load monitoring outcomes, small sample size, geographical location, and non-randomized assignment and selection of participants., Conclusions: Interventions including ANC/ART integration, family-centred approaches, and the use of lay healthcare providers are demonstrably effective in increasing service uptake and retention of HIV-positive mothers and their infants in PMTCT programmes. Future studies should include control groups and assess whether interventions developed in the context of earlier 'Options' are effective in improving outcomes in Option B+ programmes., (© 2017 John Wiley & Sons Ltd.)

Objectives: To systematically review evidence on the prevalence and characteristics of hearing impairment among children and adults living with HIV in low- and middle-income countries (LMIC)., Methods: Articles were identified up to January 2016 through searching four electronic databases. Epidemiological studies conducted in LMIC that explored the association between HIV status and hearing loss, with or without an HIV-uninfected comparison group, were eligible for inclusion. Results were screened and assessed for eligibility, and data were extracted by two reviewers, with discussion in the case of disagreement. Findings were narratively synthesised., Results: The search identified 638 unique references, of which 21 studies were included in the review, including 3491 people with HIV from 13 LMIC. There was lack of consistency in the definition used for hearing loss, making comparability across studies difficult. Among children with HIV, across the three studies that used a cut-off of >15 dB in either ear, the prevalence of hearing loss ranged from 22 to 37%. Among the three studies that used >25 dB in either ear, the prevalence ranged from 32 to 39%. Among adults with HIV, for the five studies that used a threshold of >25 dB for either ear, the prevalence ranged from 10 to 43%. The prevalence of hearing impairment was significantly higher among people with HIV than in controls in eight of the ten studies that assessed this comparison. Conductive hearing loss was the most common type of hearing loss in children with HIV, while sensorineural hearing loss was more common in adults with HIV. There was a lack of evidence for an association between ART use and hearing loss, although there was some suggestion that late stage of HIV disease or low CD4 count was related to hearing loss. There were concerns about the quality of the studies included in the review., Conclusions: The current evidence is suggestive of a high prevalence of hearing loss among people living with HIV compared to people without HIV, or to WHO estimates for the general population. More research is needed to better understand the aetiology of hearing loss in relation to HIV, and whether screening for and treatment of hearing loss can be effectively integrated into HIV treatment services needs further research., (© 2017 John Wiley & Sons Ltd.)

Objectives: To describe regional differences in the relative fertility of HIV-positive vs. HIV-negative women and changes as antiretroviral treatment (ART) is scaled up, to improve estimates of predicted need for and coverage of prevention of mother-to-child transmission services at national and subnational levels., Methods: We analysed 49 nationally representative household surveys in sub-Saharan Africa between 2003 and 2016 to estimate fertility rate ratios of HIV-positive and HIV-negative women by age using exponential regression and test for regional and urban/rural differences. We estimated the association between national ART coverage and the relationship between HIV and fertility., Results: Significant regional differences exist in HIV and fertility relationships, with less HIV-associated subfertility in Southern Africa. Age patterns of relative fertility are similar. HIV impact on fertility is weaker in urban than rural areas. For women below age 30, regional and urban/rural differences are largely explained by differences in age at sexual debut. Higher levels of national ART coverage were associated with slight attenuation of the relationship between HIV and fertility., Conclusions: Regional differences in HIV-associated subfertility and urban-rural differences in age patterns of relative fertility should be accounted for when predicting need for and coverage of PMTCT services at national and subnational level. Although HIV impacts on fertility are somewhat reduced at higher levels of national ART coverage, differences in fertility between HIV positive and negative remain, and fertility of women on ART should not be assumed to be the same as HIV-negative women. There were few data in recent years, when ART has reached high levels, and this relationship should continue to be assessed as further evidence becomes available., (© 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objectives: Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART., Methods: The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index <18.5 kg/m 2 ) and requiring ART. The relationship of grip strength to nutritional, infectious and demographic factors was assessed by multivariable linear regression at referral for ART (n = 1742) and after 12 weeks (n = 778) and 2-3 years of ART (n = 273)., Results: In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength., Conclusions: In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition., (© 2017 John Wiley & Sons Ltd.)

Objective: To describe the cascade of care to HIV mother-to-child transmission (PMTCT) in a Rio de Janeiro reference paediatric clinic and evaluate the main factors possibly associated with HIV transmission., Methods: Data on antenatal care (ANC), perinatal and neonatal assistance to HIV-infected and HIV-exposed but uninfected children assisted in the clinic from 1996 to 2013 were collected. The cascade of care was graphically demonstrated, and possible factors associated with HIV infection were described using regression models for bivariate and multivariate analysis. We imputed missing values of explanatory variables for the final model., Results: A total of 989 children were included in the analysis: 211 were HIV and 778 HEU. Graphically, the HIV PMTCT cascade of care improved from 1996/2000 to the later periods, but not from 2001/2006 to 2007/2013. The main factor independently associated with the HIV infection over time was breastfeeding. In the period 1996/2000, the lack of antiretroviral use during labour was associated HIV transmission. While in 2001/2007, other modes of delivery but elective Caesarean section, and lack of maternal antiretroviral use during ANC were associated with HIV transmission. In the last period, the main factor associated with transmission was the lack of maternal ANC., Conclusions: The HIV PMTCT cascade improved over time, but HIV vertical transmission remains a problem, and better access to ANC is needed., (© 2017 John Wiley & Sons Ltd.)

Introduction: Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV-disease or those with CD4 counts below 350/mm 3 according to 2006 WHO guidelines. We assessed the impact of CTX prophylaxis on the risk of malaria episodes in HIV-1-infected adults from four West African countries with different patterns of malaria transmission., Method: Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naïve HIV-infected adults started CTX at enrolment (CTX group) if they had CD4 < 350 cells/mm 3 or were at WHO clinical stage ≥2. For patients who did not start CTX at enrolment (non-CTX group) and started CTX afterwards, follow-up was censored at CTX initiation. We used Cox's proportional hazard model to compare the risk of malaria between CTX groups., Results: A total of 514 participants (median CD4 count 238 cells/mm 3 ) were followed for a median of 15 months. At enrolment, 347 started CTX, and 261 started ART. During the follow-up, 28 started CTX. The incidence of malaria was 8.7/100 PY (95%CI 6.3-11.5) overall, 5.2/100 PY (95%CI 3.1-8.3) in the CTX group and 15.5/100 PY (95%CI 10.3-22.1) in the non-CTX group. In multivariate analysis, CTX led to a 69% reduction in the risk of malaria (aHR 0.31, 95%CI 0.10-0.90)., Conclusion: Patients in the CTX group had an adjusted risk of malaria three times lower than those in the non-CTX group. The prolonged large-scale use of CTX did not blunt the efficacy of CTX to prevent malaria in this region., (© 2017 John Wiley & Sons Ltd.)

Objective: To assess the uptake of WHO-recommended PMTCT procedures in Ethiopia's health services., Methods: Prospective observational study of HIV-positive pregnant mothers and their newborns attending PMTCT services at seven health centres in Addis Ababa. Women were recruited during antenatal care and followed up with their newborns at delivery, Day 6 and Week 6 post-partum. Retention to PMCTC procedures, self-reported antiretroviral treatment (ART) adherence and HIV infant outcome were assessed. Turnaround times of HIV early infant diagnosis (EID) procedures were extracted from health registers., Results: Of 494 women enrolled, 4.9% did not complete PMTCT procedures due to active denial or loss to follow-up. HIV was first diagnosed in 223 (45.1%) and ART initiated in 321 (65.0%) women during pregnancy. ART was initiated in a median of 1.3 weeks (IQR 0-4.3) after HIV diagnosis. Poor self-reported treatment adherence was higher post-partum than during pregnancy (12.5% vs. 7.0%, P = 0.002) and significantly associated with divorced/separated marital status (RR 2.2, 95% CI 1.3-3.8), low family income (RR 2.1, 95% CI 1.1-4.1), low CD4 count (RR 1.7, 95% CI 1.0-3.0) and ART initiation during delivery (RR 2.5, 95% CI 1.1-5.6). Of 435 infants born alive, 98.6% received nevirapine prophylaxis. The mother-to-child HIV transmission rate was 0.7% after a median of 6.7 weeks (IQR 6.4-10.4), but EID results were received for only 46.6% within 3 months of birth., Conclusion: High retention in PMTCT services, triple maternal ART and high infant nevirapine prophylaxis coverage were associated with low mother-to-child HIV transmission. Declining post-partum ART adherence and challenges of EID linkage require attention., (© 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

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., (© 2017 John Wiley & Sons Ltd.)

Background: An infected host's Leishmania infantum load in blood is considered to be an estimate of his or her total parasite burden. Therefore, the measurement of blood parasite burden is important in the identification of factors involved in parasite control., Methods: Quantitative polymerase chain reaction was performed on blood samples from 625 patients with kala-azar consecutively admitted to a reference hospital in Teresina, Brazil. Primers were used to amplify a segment of kDNA using the TaqMan system. Non-parametric statistical tests were applied., Results: The median blood parasite burden was 499.2 amastigote equivalents (AE)/ml. Children <1 year old (yo) had a high parasite burden, which dropped sharply after the first year of life (192.8, AE/ml at 1 < 2 yo) and remained lower until adolescence. Following adolescence, the parasite burden increased with age, peaking among elderly individuals. Men had a higher parasite burden than women. HIV-infected patients had a much higher parasite burden than non-infected patients. The parasite burden of children under 5 years with acute moderate to severe malnourishment (weight-for-age and body mass index z-scores <-2) was almost three times greater than that of better-nourished children. The parasite burden identified in deceased patients was more than twice that of surviving patients; those with a higher risk of death, sepsis, pneumonia and jaundice also had increased parasite burdens. All of these differences were statistically significant at P-values <0.05., Conclusions: These data indicate that the parasite burden in patients with kala-azar was associated with age- and gender-associated factors and with HIV infection status. Acute malnutrition could be either a cause or a consequence of a higher parasite burden. An individual's parasite burden influences his or her clinical profile, disease severity and mortality risk. The best explanation for the presence of a higher parasite burden in individuals with these immunoregulatory conditions and severe disease is the occurrence of acquired immunosuppression followed by heightened innate immunity., (© 2017 John Wiley & Sons Ltd.)