Project description:IntroductionA recent sero-discordant couple study showed an elevated risk of HIV-acquisition during the pregnancy/postpartum period per-condomless-coital-act. This, along with previous studies, has led to concern over possible increased risk of mother-to-child (vertical) transmission, due to the initial high viral load in the first months after seroconversion, in a time when the woman and health services may be unaware of her status. This study looks at whether behavioural differences during the pregnant/postpartum period could reduce the impact of elevated risk of HIV acquisition per-condomless-coital-act at the population level.MethodsWe used data from 60 demographic and health surveys from 32 sub-Saharan African countries. Using the HIV status of couples, we estimated differences in serodiscordancy between HIV-negative women who were pregnant/postpartum compared to those who were not pregnant/postpartum. We compare the risk of sexual activity over the pregnant/postpartum period to those not pregnant/postpartum. Using these risks of serodiscordancy and sexual activity along with estimates of increased HIV risk in the pregnancy/postpartum period per-condomless-coital-act, we estimated a population-level risk of HIV acquisition and acute infection, during pregnancy/postpartum compared to those not pregnant/postpartum.ResultsSexual activity during pregnancy/postpartum varies considerably. In general, sexual activity is high in the first trimester of pregnancy, then declines to levels lower than among women not pregnant/postpartum, and is at its lowest in the first months postpartum. Adjusted for age and survey, pooled results show HIV-negative pregnant women are less likely to have an HIV-positive partner compared to those not pregnant/postpartum (risk ratio (RR) = 0.78, 95% CI = 0.68-0.89) and comparing the postpartum period (RR = 0.85, 95% CI = 0.73-0.99). Estimated population-level risk for HIV acquisition and acute infection in pregnancy/postpartum was lower than would be inferred directly from per-condomless-coital-act estimates in most countries, over the time of most risk of mother-to-child transmission, though there was variation by country and month of pregnancy/postpartum.ConclusionsEstimates of population-level HIV acquisition risk in sub-Saharan Africa should not be taken directly from per-condomless-coital-act studies to estimate vertical transmission. Changes in sexual behaviour and differences in HIV-serodiscordancy during pregnancy/postpartum reduce the impact of increased risk of HIV acquisition per-condomless-coital-act, this will vary by region.

Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.

Project description:BackgroundThe rate of mother-to-child transmission of HIV, occurring during pregnancy, delivery/labour and breastfeeding, still remains high in Sub-Saharan Africa (SSA). The World Health Organization recommends HIV infected mothers exclusively breastfeed their infants, unless replacement feeding is Acceptable, Feasible, Affordable, Sustainable and Safe (AFASS). Health care workers are responsible for providing counselling to mothers on the risks and benefits of infant feeding options allowing mothers to make an 'informed choice', but this role is challenging and mostly subjective. The aim of this study was to develop and content validate an AFASS assessment tool that could be used for infant feeding counselling in SSA.MethodsAn AFASS assessment tool was developed based on the evidence and tools available regarding why replacement feeding is not AFASS in SSA (15 questions). Fifty seven experts involved in PMTCT programmes in five SSA countries were approached to participate as members of the Delphi expert panel (purposive sampling and snowballing). A web-based survey, utilising a 4-point Likert scale, was employed to gain consensus (>75% agreement) from the expert panel following the Delphi technique.ResultsA final panel of 15 experts was obtained. Thirteen of the 15 questions in the tool achieved consensus agreement. Experts suggested some additional questions, and that double-barrelled questions were split. Consensus was achieved regarding the applicability and appropriateness of the tool within a SSA context. Experts all agreed that the tool will be useful for the purpose for which it was designed. Suggestions made by the expert panel were incorporated into the revised tool.ConclusionsThe findings of this study confirm that this AFASS counselling tool may be appropriate and useful for SSA. Ideally the revised tool should be tested by providers of infant feeding advice with the aim of adoption into routine PMTCT programmes in SSA. Within the context of the 2010 WHO guidelines which advocate a public health rather than an individualised approach, it may inform the WHO process of improving counselling tools for health care workers involved in PMTCT programmes.

Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects

Project description:UnlabelledWe quantified the collective impact of source partner HIV-1 RNA levels, human leukocyte antigen (HLA) alleles, and innate responses through Toll-like receptor (TLR) alleles on the HIV-1 set point. Data came from HIV-1 seroconverters in African HIV-1 serodiscordant couple cohorts. Linear regression was used to determine associations with set point and R(2) to estimate variation explained by covariates. The strongest predictors of set point were HLA alleles (B*53:01, B*14:01, and B*27:03) and plasma HIV-1 levels of the transmitting partner, which explained 13% and 10% of variation in set point, respectively. HLA-A concordance between partners and TLR polymorphisms (TLR2 rs3804100 and TLR7 rs179012) also were associated with set point, explaining 6% and 5% of the variation, respectively. Overall, these factors and genital factors of the transmitter (i.e., male circumcision, bacterial vaginosis, and use of acyclovir) explained 46% of variation in set point. We found that both innate and adaptive immune responses, together with plasma HIV-1 levels of the transmitting partner, explain almost half of the variation in viral load set point.ImportanceAfter HIV-1 infection, uncontrolled virus replication leads to a rapid increase in HIV-1 concentrations. Once host immune responses develop, however, HIV-1 levels reach a peak and subsequently decline until they reach a stable level that may persist for years. This stable HIV-1 set point represents an equilibrium between the virus and host responses and is predictive of later disease progression and transmission potential. Understanding how host and virus factors interact to determine HIV-1 set point may elucidate novel mechanisms or biological pathways for treating HIV-1 infection. We identified host and virus factors that predict HIV-1 set point in people who recently acquired HIV-1, finding that both innate and adaptive immune responses, along with factors that likely influence HIV-1 virulence and inoculum, explain ∼46% of the variation in HIV-1 set point.

Project description:Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized. Although a number of significant associations were determined in both the total group and in the nevirapine (NVP) exposed group, the most significant findings involved KIR2DL2 and KIR2DL3 and HLA-C. KIR2DL2/KIR2DL3 was underrepresented in intrapartum (IP)-transmitting mothers compared to non-transmitting (NT) mothers (P?=?0.008) and remained significant (P?=?0.036) after correction for maternal viral load (MVL). Homozygosity for KIR2DL3 alone and in combination with HLA-C allotype heterozygosity (C1C2) was elevated in IP-transmitting mothers compared to NT mothers (P?=?0.034 and P?=?0.01 respectively), and after MVL correction (P?=?0.033 and P?=?0.027, respectively). In infants, KIR2DL3 in combination with its HLA-C1 ligand (C1) as well as homozygosity for KIR2DL3 with C1C2, were both found to be underrepresented in infected infants compared to exposed uninfected infants in the total group (P?=?0.06 and P?=?0.038, respectively) and in the sub-group of infants whose mothers received NVP (P?=?0.007 and P?=?0.03, respectively). These associations were stronger post MVL adjustment (total group: P?=?0.02 and P?=?0.009, respectively; NVP group: P?=?0.004 and P?=?0.02, respectively). Upon stratification according to low and high MVL, all significant associations fell within the low MVL group, suggesting that with low viral load, the effects of genotype can be more easily detected. In conclusion this study has identified a number of significant associations that suggest an important role for NK cells in maternal-to-infant HIV-1 transmission.

Project description:BackgroundIn sub-Saharan Africa (SSA) 90 percent of babies acquired HIV/AIDS from infected mothers. Maternal knowledge about mother to child transmission (MTCT) of HIV/AIDS and its prevention is a cornerstone for elimination of MTCT of HIV/AIDS. Despite this, there is limited evidence about knowledge about MTCT of HIV/AIDS and its prevention and associated factors in SSA. Therefore, this study aimed to assess knowledge of MTCT of HIV/AIDS, its prevention (PMTCT) and, associated factors among reproductive-age women in sub-Saharan Africa.ObjectiveTo assess Knowledge about mother to child transmission of HIV/AIDS and its prevention and associated factors among reproductive-age women in Sub-Saharan Africa.MethodsThe recent SSA countries' Demographic and Health Surveys (DHS), which were conducted from 2008/09 to 2018/19, was our data source. We appended 33 countries' DHS data for our analysis. For our study, a total weighted sample of 350,888 reproductive-age women was used. Due to the hierarchical nature of the DHS data, we conducted a multilevel analysis. Finally, the adjusted odds ratio with its 95% confidence interval was reported, and variables with p-value≤0.05 were considered as significant predictors of knowledge of MTCT of HIV/AIDS and its prevention.ResultsIn this study, 56.21% (95% CI: 56.05-56.38) of respondents had correct knowledge about MTCT of HIV/AIDS and its prevention among reproductive-age women in SSA. In the multilevel logistic regression analysis: being in the older age group, better education level, being from a rich household, having mass media exposure, having parity of one and above were associated with higher odds of knowledge about MTCT of HIV/AIDS and its prevention. However, being perceiving distance from the health facility as a big problem was associated with lower odds of knowledge about MTCT of HIV/AIDS and its prevention.ConclusionKnowledge about MTCT of HIV/AIDS and its prevention among reproductive-age women in SSA was low. Therefore, it is better to consider the high-risk groups during the intervention to increase awareness about this essential public health issue and to tackle its devastating outcome.

Project description:Despite concerns about the coexistence of overnutrition, undernutrition and micronutrient deficiencies, which is compositely referred to as the triple burden of malnutrition (TBM), little is known about the phenomenon in sub-Saharan Africa (SSA). We, therefore, aimed to examine the prevalence and investigate the factors associated with TBM in SSA. This study uses cross-sectional survey data collected through the Demographic and Health Surveys (DHS) Program from 2010 to 2019. Data from 32 countries in SSA were used for the analysis. The prevalence of TBM were presented in tables and maps using percentages. The predictors of TBM were examined by fitting a negative log-log regression to the data. The results were then presented using adjusted odds ratios (aORs) at 95% Confidence Intervals (CIs). Out of the 169,394 children, 734 (1%) suffered from TBM. The highest proportion of children with TBM in the four geographic regions in SSA was found in western Africa (0.75%) and the lowest in central Africa (0.21%). Children aged 1 [aOR = 1.283; 95% CI = 1.215-1.355] and those aged 2 [aOR = 1.133; 95% CI = 1.067-1.204] were more likely to experience TBM compared to those aged 0. TBM was less likely to occur among female children compared to males [aOR = 0.859; 95% CI = 0.824-0.896]. Children whose perceived size at birth was average [aOR = 1.133; 95% CI = 1.076-1.193] and smaller than average [aOR = 1.278; 95% CI = 1.204-1.356] were more likely to suffer from TBM compared to those who were larger than average at birth. Children born to mothers with primary [aOR = 0.922; 95% CI = 0.865-0.984] and secondary [aOR = 0.829; 95% CI = 0.777-0.885] education were less likely to suffer from TBM compared to those born to mothers with no formal education. Children born to mothers who attended antenatal care (ANC) had lower odds of experiencing TBM compared to those born to mothers who did not attend ANC [aOR = 0.969; 95% CI = 0.887-0.998]. Children born to mothers who use clean household cooking fuel were less likely to experience TBM compared to children born to mothers who use unclean household cooking fuel [aOR = 0.724; 95% CI = 0.612-0.857]. Essentially, higher maternal education, ANC attendance and use of clean cooking fuel were protective factors against TBM, whereas higher child age, low size at birth and being a male child increased the risk of TBM. Given the regional variations in the prevalence and risk of TBM, region-specific interventions must be initiated to ensure the likelihood of those interventions being successful at reducing the risk of TBM. Countries in Western Africa in particular would have to strengthen their current policies and programmes on malnutrition to enhance their attainment of the SDGs.

Dataset Information

Host Molecular Factors and Viral Genotypes in the Mother-to-Child HIV-1 Transmission in Sub-Saharan Africa.

Publications

Host Molecular Factors and Viral Genotypes in the Mother-to-Child HIV-1 Transmission in Sub-Saharan Africa.

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