Cohort profile: the Siyakhula cohort, rural South Africa

No abstract available

Rates of mother-to-child transmission of HIV-1 in Africa, America and Europe : results from 13 perinatal studies

The goal of this exercise was to provide estimates of the mother-to-child transmission rate (TR) of human immunodeficiency virus type 1 (HIV-1), calculated according to standardized methods. Prospective cohort studies in Africa, the Caribbean, Europe, and the USA observed from birth children born to women known to be HIV infected at the time of delivery. TRs were calculated and compared by investigators during a meeting in Ghent (Belgium) in September 1993 according to agreed methodology. TRs were calculated following the direct and the indirect methods developed in 1992 by the Ghent Working Group. The direct method uses a classification of children born to HIV-seropositive mothers according to their probable HIV infection status at 15 months of age or before, if they die or are lost to follow-up. Minimum, intermediate, and maximum estimates of TR are computed depending on how children classified as indeterminate are counted. The indirect method is applied for studies with a comparison cohort of children born to HIV-seronegative mothers. TRs in developed countries ranged from 14 to 25% with the direct method (intermediate estimate). In the developing world, they ranged from 13 to 42% with the direct method, from 21 to 43% with the indirect method, and most of the studies reported a TR in the range of 25 to 30%. With use of a standardized methodology, the overall TR of HIV-1 tends to be higher in Africa than in Europe or the USA. The variation in TRs is probably due to differences in factors associated with increased risk of transmission. This is of importance for the design and implementation of trials evaluating interventions aimed at reducing mother-to-child transmission of HIV. (Résumé d'auteur

Time to eligibility for antiretroviral therapy in adults with CD4+ cell count >500 cells/µl in rural KwaZulu-Natal, South Africa

ObjectivesUnderstanding of progression to antiretroviral therapy (ART) eligibility and associated factors remains limited. The objectives of this analysis were to determine the time to ART eligibility and to explore factors associated with disease progression in adults with early HIV infection.MethodsHIV-infected adults (??18 years old) with CD4 cell count >?500 cells/?l were enrolled in the study at three primary health care clinics, and a sociodemographic, behavioural and partnership-level questionnaire was administered. Participants were followed 6-monthly and ART eligibility was determined using a CD4 cell count threshold of 350 cells/?l. Kaplan???Meier and Cox proportional hazard regression modelling were used in the analysis.ResultsA total of 206 adults contributed 381 years of follow-up; 79 (38%) reached the ART eligibility threshold. Median time to ART eligibility was shorter for male patients (12.0 months) than for female patients (33.9 months). Male sex [adjusted hazard ratio (aHR) 3.13; 95% confidence interval (CI) 1.82–5.39], residing in a household with food shortage in the previous year (aHR 1.58; 95% CI 0.99–2.54), and taking nutritional supplements in the first 6 months after enrolment (aHR 2.06; 95% CI 1.11–3.83) were associated with shorter time to ART eligibility. Compared with reference CD4 cell count????559 cells/?l, higher CD4 cell count was associated with longer time to ART eligibility [aHR 0.46 (95% CI 0.25–0.83) for CD4 cell count 560–632 cells/?l; aHR 0.30 (95% CI 0.16–0.57) for CD4 cell count 633–768 cells/?l; and aHR 0.17 (95% CI 0.08–0.38) for CD4 cell count?>?768 cells/?l].ConclusionsOver one in three adults with CD4 cell count?>?500 cells/?l became eligible for ART at a CD4 cell count threshold of 350 cells/?l over a median of 2 years. The shorter time to ART eligibility in male patients suggests a possible need for sex-specific pre-ART care and monitoring strategies

Metabolic Responses to Carbohydrate Ingestion during Exercise: Associations between Carbohydrate Dose and Endurance Performance

Carbohydrate (CHO) ingestion during exercise lasting less than three hours improves endurance exercise performance but there is still debate about the optimal dose. We utilised stable isotopes and blood metabolite profiles to further examine metabolic responses to CHO (glucose only) ingestion in the 20–64 g·h−1 range, and to determine the association with performance outcome. In a double-blind, randomized cross-over design, male cyclists (n = 20, mean ± SD, age 34 ± 10 years, mass 75.8 ± 9 kg, peak power output 394 ± 36 W, VO2max 62 ± 9 mL·kg−1·min−1) completed four main experimental trials. Each trial involved a two-hour constant load ride (185 ± 25 W) followed by a time trial, where one of three CHO beverages, or a control (water), were administered every 15 min, providing 0, 20, 39 or 64 g CHO·h−1. Dual glucose tracer techniques, indirect calorimetry and blood analyses were used to determine glucose kinetics, exogenous CHO oxidation (EXO), endogenous CHO and fat oxidation; and metabolite responses. Regression analysis revealed that total exogenous CHO oxidised in the second hour of exercise, and suppression of serum NEFA concentration provided the best prediction model of performance outcome. However, the model could only explain ~19% of the variance in performance outcome. The present data demonstrate that consuming ~40 g·h−1 of CHO appears to be the minimum ingestion rate required to induce metabolic effects that are sufficient to impact upon performance outcome. These data highlight a lack of performance benefit and few changes in metabolic outcomes beyond an ingestion rate of 39 g·h−1. Further work is required to explore dose-response effects of CHO feeding and associations between multiple metabolic parameters and subsequent performance outcome

The association between self-reported stigma and loss-to-follow up in treatment eligible HIV positive adults in rural KwaZulu-Natal, South Africa

BackgroundThe relationship between loss-to-follow-up (LTFU) in HIV treatment and care programmes and psychosocial factors, including self-reported stigma, is important to understand. This prospective cohort study explored stigma and LTFU in treatment eligible adults who had yet not started antiretroviral therapy (ART).MethodsPsychosocial, clinical and demographic data were collected at a baseline interview. Self-reported stigma was measured with a multi-item scale. LTFU was defined as not attending clinic in the 90 days since last appointment or before death. Data was collected between January 2009 and January 2013 and analysed using Cox Regression.Results380 individuals were recruited (median time in study 3.35 years, total time at risk 1065.81 person-years). 203 were retained (53.4%), 109 were LTFU (28.7%), 48 had died and were not LTFU at death (12.6%) and 20 had transferred out (5.3%). The LTFU rate was 10.65 per 100 person-years (95% CI: 8.48–12.34). 362 individuals (95.3%) started ART. Stigma total score (categorised in quartiles) was not significantly associated with LTFU in either univariable or multivariable analysis (adjusting for other variables in the final model): second quartile aHR 0.77 (95%CI: 0.41–1.46), third quartile aHR 1.20(95%CI: 0.721–2.04), fourth quartile aHR 0.62 (95%CI: 0.35–1.11). In the final multivariable model, higher LTFU rates were associated with male gender, increased openness with friends/family and believing that community problems would be solved at higher levels. Lower LTFU rates were independently associated with increased year of age, greater reliance on family/friends, and having children.ConclusionsDemographic and other psychosocial factors were more closely related to LTFU than self-reported stigma. This may be consistent with high levels of social exposure to HIV and ART and with stigma affecting LTFU less than other stages of care. Research and clinical implications are discussed

HIV ascertainment through repeat home-based testing in the context of a treatment as prevention trial (ANRS 12249 TasP) in rural South Africa

International audienceBackgroundThe ANRS 12249 TasP cluster-randomised trial evaluates whether HIV testing of all members of a community, followed by immediate antiretroviral treatment (ART) for infected people, will prevent onward sexual transmission and reduce HIV incidence at population level. Ascertaining the HIV status of a high proportion of the population regularly and repeatedly is key to the success of any universal test and treat strategy, as the first step of the HIV cascade.MethodsBetween March 2012 and March 2014, we implemented three six-monthly rounds of home-based HIV counselling and testing in ten local communities (clusters). At each home visit, individual questionnaires were administered and a rapid HIV test offered to all trial participants. We report early results on rates of HIV ascertainment, defined as undergoing a rapid HIV test or HIV-positive self-report.ResultsOf 12,911 eligible individuals (resident in the trial area and ≥16 years), 10,007 were successfully contacted at least once. At first contact, HIV status was ascertained for 7,628 (76.2% [95% CI: 75.4-77.1]) individuals. At second contact, among the 5,885 individuals contacted a second time, HIV status was ascertained for 2,829 (85.0% [95% CI: 83.7-86.2]) of the 3,328 tested negative at first contact and for 543 (45.7% [95% CI: 42.9-48.6]) of the 1,188 who refused a rapid test at first contact. Overall, HIV ascertainment rate was 89.0% (5,239/5,885 [95% CI: 88.2-89.8]) among trial participants contacted twice.ConclusionsRepeat home-based HIV testing is acceptable and feasible in this rural area. Socio-demographic characteristics, behaviours, attitudes, household characteristics and experience of HIV infection and ART in the household will be explored for their association with HIV ascertainment uptake. This will inform whether this intervention reaches the individuals at higher risk in a rural South African region

Evaluation of human and non-human primate antibody binding to pig cells lacking GGTA1/CMAH/β4GalNT2 genes

Background Simultaneous inactivation of pig GGTA1 and CMAH genes eliminates carbohydrate xenoantigens recognized by human antibodies. The β4GalNT2 glycosyltransferase may also synthesize xenoantigens. To further characterize glycan-based species incompatibilities, we examined human and non-human primate antibody binding to cells derived from genetically modified pigs lacking these carbohydrate-modifying genes. Methods The Cas9 endonuclease and gRNA were used to create pigs lacking GGTA1, GGTA1/CMAH, or GGTA1/CMAH/β4GalNT2 genes. Peripheral blood mononuclear cells were isolated from these animals and examined for binding to IgM and IgG from humans, rhesus macaques, and baboons. Results Cells from GGTA1/CMAH/β4GalNT2 deficient pigs exhibited reduced human IgM and IgG binding compared to cells lacking both GGTA1 and CMAH. Nonhuman primate antibody reactivity with cells from the various pigs exhibited a slightly different pattern of reactivity than that seen in humans. Simultaneous inactivation of the GGTA1 and CMAH genes increased nonhuman primate antibody binding compared to cells lacking either GGTA1 only or to those deficient in GGTA1/CMAH/β4GalNT2. Conclusions Inactivation of the β4GalNT2 gene reduces human and nonhuman primate antibody binding resulting in diminished porcine xenoantigenicity. The increased humoral immunity of nonhuman primates towards GGTA1/CMAH-deficient cells compared to pigs lacking either GGTA1 or GGTA1/CMAH/β4GalNT2 highlights the complexities of carbohydrate xenoantigens and suggests potential limitations of the nonhuman primate model for examining some genetic modifications. The progressive reduction of swine xenoantigens recognized by human immunoglobulin through inactivation of pig GGTA1/CMAH/β4GalNT2 genes demonstrates that the antibody barrier to xenotransplantation can be minimized by genetic engineering