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INTRODUCTION: HIV-exposed uninfected (HEU) children have higher morbidity and mortality compared with HIV unexposed uninfected children. Despite the fact that malnutrition contributes to about half of all infant deaths below 5 years of age in low-income and middle-income countries and that growth impairment has been reported in the HEU population, the spectrum of growth disorders associated with HIV and antiretroviral therapy (ART) exposure during the in utero and perinatal periods is yet to comprehensively summarised among the global HEU population. This protocol for a systematic review and meta-analysis aims to critically synthesise data concerning the prevalence of underweight, stunting and wasting at different ages in the global HEU population. METHODS AND ANALYSIS: Medline, EMBASE, Cochrane Library, TOXLINE, WHO Global Index Medicus and the Web of Science will be searched for relevant articles published between 1 January 1989 and 1 December 2017 without language restriction. In addition, conference abstracts and reference lists of eligible papers and relevant review articles will be screened. Authors will screen and select studies, extract data, assess the risk of bias as well as studies individually for heterogeneity. Study-specific estimates will be pooled through a random-effects meta-analysis model for studies that are clinically homogeneous while funnel plots and Egger's test will be used to detect publication bias. Results will be presented by ART availability period, country income levels and mode of breastfeeding. ETHICS AND DISSEMINATION: Ethical approval will not be required for this study because it will be based on published data. The final report of this study will be published in a peer-reviewed journal and presented at scientific conferences. This review will summarise the evidence and quantify the problem of growth impairment in HEU infants and so shed more light on our understanding of the higher morbidity and mortality in this growing population. PROSPERO REGISTRATION NUMBER: CRD42018091762.

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Although mother-to-child transmission of HIV has dramatically declined, the number of in utero HIV-exposed, uninfected infants is on the increase. HIV-exposed infants are at an increased risk of mortality, morbidity and slower early growth than their non-HIV exposed counterparts. Maternal HIV increases the risk of having preterm deliveries, intrauterine growth restriction and low birth weight babies. However, the mechanism underlying dysregulation of fetal growth in HIV-infected pregnant women is unknown. We sought to determine whether maternal HIV is associated with dysregulation of the insulin-like growth factor (IGF) axis, some angiogenic factors or other related biomarkers that regulate fetal growth. A total of 102 normotensive pregnant women were enrolled in a small cross-sectional study. Amongst these were thirty-one HIV-1 positive women receiving combination antiretroviral therapy (cART) (Mean age: 30.0 ± 5.1 years; % on ART: 83.9%; median plasma viral load: 683 copies/ml; median CD4 count: 350 cells/ul) and 71 HIV uninfected women (mean age: 27.3 ± 5.8) recruited at delivery. A panel of biomarkers including IGF1 and IGF binding proteins (IGFBP1, IGFBP3), angiopoietins (ANG) 1 and 2, matrix metalloproteinases (MMP) 2 and 9, and galectin 13, was measured in plasma collected from the placental intervillous space. The levels of IGF1, IGFBP1, ANG1, ANG2, MMP2, MMP9 and Gal-13 were not affected by maternal HIV, even when adjusted for maternal factors in linear regression models (all p>0.05). It was observed that HIV-infection in pregnancy did not significantly affect key markers of the IGF axis and angiogenic factors. If anything, it did not affect women. These findings highlight the importance of the use of ART during pregnancy, which maintains factors necessary for fetal development closer to those of healthy women. However, decrease in IGF1 levels might be exacerbated in women con-infected with HIV and malaria.

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BACKGROUND: In low-income countries (LICs), HIV sentinel surveillance surveys (HIV-SSS) are recommended in between two demographic and health surveys, due to low-cost than the latter. Using the classical unlinked anonymous testing (UAT), HIV-SSS among pregnant women raised certain ethical and financial challenges. We therefore aimed at evaluating how to use prevention of mother-to-child transmission of HIV (PMTCT) routine data as an alternative approach for HIV-SSS in LICs. METHODS: A survey conducted through 2012 among first antenatal-care attendees (ANC1) in the ten regions of Cameroon. HIV testing was performed at PMTCT clinics as-per the national serial algorithm (rapid test), and PMTCT site laboratory (PMTCT-SL) performances were evaluated by comparison with results of the national reference laboratory (NRL), determined as the reference standard. RESULTS: Acceptance rate for HIV testing was 99%, for a total of 6521 ANC1 (49 · 3% aged 15-24) enrolled nationwide. Among 6103 eligible ANC1, sensitivity (using NRL testing as the reference standard) was 81 · 2%, ranging from 58 · 8% (South region) to 100% (West region); thus implying that 18 · 8% HIV-infected ANC1 declared HIV-negative at the PMTCT-SL were positive from NRL-results. Specificity was 99 · 3%, without significant disparity across sites. At population-level, this implies that every year in Cameroon, ~2,500 HIV-infected women are wrongly declared seronegative, while ~1,000 are wrongly declared seropositive. Only 44 · 4% (16/36) of evaluated laboratories reached the quality target of 80%. CONCLUSIONS: The study identified weaknesses in routine PMTCT HIV testing. As Cameroon transitions to using routine PMTCT data for HIV-SSS among pregnant women, there is need in optimizing quality system to ensure robust routine HIV testing for programmatic and surveillance purposes.

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BACKGROUND: Knowledge of the characteristics of patients co-infected with tuberculosis (TB) and human immunodeficiency virus (HIV) when TB treatment is initiated would allow clinicians to improve care and help policy-makers develop relevant and realistic guidelines. The aim of this study was to describe socio-demographic, clinical, and laboratory characteristics of TB/HIV co-infected patients starting inpatient TB treatment in Yaoundé, Cameroon. METHODS: We conducted a retrospective cross-sectional study, collecting data from medical records of HIV-infected patients with TB, aged 15 years old or more, hospitalized in the Infectious Diseases Unit of the Yaoundé Central Hospital, Cameroon from January 1, 2006 to June 30, 2013. RESULTS: The mean age of 337 patients meeting study inclusion criteria was 39.3 years. More than half were female (53.4%). Most (89.3%) resided in urban areas, 44.2% had a secondary education, and 46.0% were married. The majority was receiving co-trimoxazole prophylaxis (79.5%), and two thirds were taking antiretroviral therapy (67.4%). The mean duration of known HIV infection before TB treatment was 8.4 months. Most (88.1%) had newly diagnosed TB, rather than relapsed disease. Smear-positive pulmonary TB was documented in a third, (35.3%). Laboratory data revealed a median white blood cell count of 5,100 cells/mm(3) (IQR 3,300-7,990 cells/mm(3)), a median hemoglobin level of 8 g/dl (IQR 7-10 g/dl), and a median CD4 cell count of 102 cells/mm(3) (IQR 33-178 cells/mm(3)). Sex differences in our study included older age in the men (p < 0.001), more of whom were married (p < 0.001) and had achieved a higher level of education (p = 0.042). Men had fewer diagnoses of smear-positive pulmonary TB (p = 0.020). They weighed more than the women (p = 0.001) and had higher hemoglobin levels (p = 0.003). CONCLUSIONS: Suboptimal adherence to WHO treatment recommendations in our Cameroonian study reinforces the importance of prescribing co-trimoxazole in HIV infection and ART for all TB/HIV co-infected persons. We urge that Ministries of Health continue implementing and disseminating guidelines for management of TB/HIV co-infected patients, and we call for measures ensuring that healthcare facilities' stocks of ART and co-trimoxazole are sufficient to meet the need for both.

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BACKGROUND: Contributors to fatal outcomes in TB/HIV co-infected patients actively undergoing TB treatment are poorly characterized. The aim was to assess factors associated with death in TB/HIV co-infected patients during the initial 6 months of TB treatment. METHODS: We conducted a hospital-based retrospective cohort study from January 2006 to December 2013 at the Yaoundé Central Hospital, Cameroon. We reviewed medical records to identify hospitalized co-infected TB/HIV patients aged 15 years and older. Death was defined as any death occurring during TB treatment, as per the World Health Organization's recommendations. We conducted logistic regression analysis to identify factors associated with a fatal outcome. Magnitudes of associations were expressed by adjusted odds ratio (aOR) with 95% confidence interval. RESULTS: The 337 patients enrolled had a mean age of 39.3 (standard deviation 10.3) years and 54.3% were female. TB treatment outcomes were distributed as follows: 205 (60.8%) treatment success, 99 (29.4%) deaths, 18 (5.3%) not evaluated, 14 (4.2%) lost to follow-up, and 1 (0.3%) failed. After exclusion of patients lost to follow-up and not evaluated, death in TB/HIV co-infected patients during TB treatment was associated with a TB diagnosis made before 2010 (aOR = 2.50 [1.31-4.78]; p = 0.006), the presence of other AIDS-defining diseases (aOR = 2.73 [1.27-5.86]; p = 0.010), non-AIDS comorbidities (aOR = 3.35 [1.37-8.21]; p = 0.008), not receiving cotrimoxazole prophylaxis (aOR = 3.61 [1.71-7.63]; p = 0.001), not receiving antiretroviral therapy (aOR = 2.45 [1.18-5.08]; p = 0.016), and CD4 cells count <50 cells/mm3 (aOR = 16.43 [1.05-258.04]; p = 0.047). CONCLUSIONS: The TB treatment success rate among TB/HIV co-infected patients in our setting is low. Mortality was high among TB/HIV co-infected patients during TB treatment and is strongly associated with clinical and biological factors, highlighting the urgent need for specific interventions focused on enhancing patient outcomes.

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