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Background: Accumulating data suggest that immune effector functions mediated through the Fc portion of HIV-1-specific immunoglobulin G (IgG) are a key component of HIV-1 protective immunity, affecting both disease progression and HIV-1 acquisition. Through studying Fc gamma receptor (Fc?R) variants known to alter IgG Fc-mediated immune responses, we indirectly assessed the role of Fc?R-mediated effector functions in modulating perinatal HIV-1 transmission risk. In this study, genotypic data from 79 HIV-1 infected mothers and 78 HIV-1 infected infants (transmitting cases) were compared to 234 HIV-1 infected mothers and 235 HIV-1 exposed-uninfected infants (non-transmitting controls). Associations, unadjusted and adjusted for multiple comparisons, were assessed for overall transmission and according to mode of transmission—intrapartum (n = 31), in utero (n = 20), in utero-enriched (n = 48). Results: The maternal FcγRIIIa-158V allele that confers enhanced antibody binding affinity and antibody-dependent cellular cytotoxicity capacity significantly associated with reduced HIV-1 transmission [odds ratio (OR) 0.47, 95 % confidence interval (CI) 0.28-0.79, P = 0.004; PBonf > 0.05]. In particular, the FcγRIIIa-158V allele was underrepresented in the in utero transmitting group (P = 0.048; PBonf > 0.05) and in utero-enriched transmitting groups (P = 0.0001; PBonf < 0.01). In both mother and infant, possession of an FcγRIIIb-HNA1b allotype that reduces neutrophil-mediated effector functions associated with increased transmission (OR 1.87, 95 % CI 1.08-3.21, P = 0.025; PBonf > 0.05) and acquisition (OR 1.91, 95 % CI 1.11-3.30, P = 0.020; PBonf > 0.05), respectively. Conversely, the infant FcγRIIIb-HNA1a∣1a genotype was significantly protective of perinatal HIV-1 acquisition (OR 0.42, 95 % CI 0.18-0.96, P = 0.040; PBonf > 0.05). Conclusions: The findings of this study suggest a potential role for FcγR-mediated effector functions in perinatal HIV-1 transmission. However, future studies are required to validate the findings of this study, in particular associations that did not retain significance after adjustment for multiple comparisons. [ABSTRACT FROM AUTHOR]

Background: We explored exposure to and experiences of violence and their risk factors amongst ethnically diverse adolescents from lower socio economic groups in Johannesburg. Methods: This cross-sectional study recruited a stratified sample of 16-18 year old adolescents from four low socio-economic suburbs in Johannesburg to reflect ethnic group clustering. We collected socio-demographic, sexual behaviour, alcohol and drug use and trauma events data. Proportions and risk factors were assessed by chi-square and logistic regression. Results: Of 822 adolescents, 57% (n = 469) were female. Approximately 62% (n = 506) were Black, 13% (n = 107) Coloured, 13% (n = 106) Indian and 13% (n = 103) White. Approximately 67% (n = 552) witnessed violence to a non-family member, 28% (n = 228) experienced violence by a non-family member, and 10% (n = 83) reported sexual abuse. Multivariate analysis determined that witnessing violence in the community was associated with being Black (OR: 4.6, 95%CI: 2.7-7.9), Coloured (OR: 3.9, 95%CI: 2.0-7.4) or White (OR: 8.0, 95%CI:4.0-16.2), repeating a grade (OR: 1.5, 95%CI: 1.01-2.1), having more than one sexual partner (OR: 1.7, 95%CI: 1.1-2.5) and ever taking alcohol (OR: 2.1, 95%CI: 1.5-2.9). Witnessing violence in the family was associated with being female (OR: 1.8, 95%CI: 1.3-2.6), being Black (OR: 2.2, 95%CI: 1.1-4.1), or White (OR: 3.0, 95%CI: 1.4-6.4), repeating a grade (OR: 1.6, 95%CI: 1.1-2.2) and ever taking alcohol (OR: 2.9, 95%CI: 2.0-4.3). Conclusions: In low socio-economic areas in Johannesburg, Black, White and Coloured adolescents experience a high burden of violence. Interventions to mitigate the effects of violence are urgently required. [ABSTRACT FROM AUTHOR]

Background: Bacterial vaginosis (BV), which is highly prevalent in the African population, is one of the most common vaginal syndromes affecting women in their reproductive age placing them at increased risk for sexually transmitted diseases including infection by human immunodeficiency virus-1. The vaginal microbiota of a healthy woman is often dominated by the species belonging to the genus Lactobacillus namely L. crispatus, L. gasseri, L. jensenii and L. iners, which have been extensively studied in European populations, albeit less so in South African women. In this study, we have therefore identified the vaginal Lactobacillus species in a group of 40 African women from Soweto, a township on the outskirts of Johannesburg, South Africa. Methods: Identification was done by cultivating the lactobacilli on Rogosa agar, de Man-Rogosa-Sharpe (MRS) and Blood agar plates with 5% horse blood followed by sequencing of the 16S ribosomal DNA. BV was diagnosed on the basis of Nugent scores. Since some of the previous studies have shown that the lack of vaginal hydrogen peroxide (H2O2) producing lactobacilli is associated with bacterial vaginosis, the Lactobacillus isolates were also characterised for their production of H2O2. Results: Cultivable Lactobacillus species were identified in 19 out of 21 women without BV, in three out of five women with intermediate microbiota and in eight out of 14 women with BV. We observed that L. crispatus, L. iners, L. jensenii, L. gasseri and L. vaginalis were the predominant species. The presence of L. crispatus was associated with normal vaginal microbiota (P = 0.024). High level of H2O2 producing lactobacilli were more often isolated from women with normal microbiota than from the women with BV, although not to a statistically significant degree (P = 0.064). Conclusion: The vaginal Lactobacillus species isolated from the cohort of South African women are similar to those identified in European populations. In accordance with the other published studies, L. crispatus is related to a normal vaginal microbiota. Hydrogen peroxide production was not significantly associated to the BV status which could be attributed to the limited number of samples or to other antimicrobial factors that might be involved. [ABSTRACT FROM AUTHOR]

Background: Efavirenz is the preferred non-nucleoside reverse transcriptase inhibitor for first-line antiretroviral treatment in many countries. For women of childbearing potential, advantages of efavirenz are balanced by concerns that it is teratogenic. This paper reviews evidence of efavirenz teratogenicity and considers implications in common clinical scenarios. Findings: Concerns of efavirenz-induced fetal effects stem from animal studies, although the predictive value of animal data for humans is unknown. Four retrospective cases of central nervous system birth defects in infants with first trimester exposure to efavirenz have been interpreted as being consistent with animal data. In a prospective pregnancy registry, which is subject to fewer potential biases, no increase was detected in overall risk of birth defects following exposure to efavirenz in the first-trimester. Discussion: For women planning a pregnancy or not using contraception, efavirenz should be avoided if alternatives are available. According to WHO guidelines for resource-constrained settings, benefits of efavirenz are likely to outweigh risks for women using contraception. Women who become pregnant while receiving efavirenz often consider drug substitution or temporarily suspending treatment. Both options have substantial risks for maternal and fetal health which, we argue, appear unjustified after the critical period of organogenesis (3-8 weeks post-conception). Efavirenz-based triple regimens, initiated after the first trimester of pregnancy and discontinued after childbirth, are potentially an important alternative for reducing mother-to-child transmission in pregnant women who do not yet require antiretroviral treatment. Conclusion: Current recommendations for care for women who become pregnant while receiving efavirenz may need to be re-considered, particularly in settings with limited alternative drugs and laboratory monitoring. With current data limitations, additional adequately powered prospective studies are needed. [ABSTRACT FROM AUTHOR]

The public sector delivery of male circumcision in the only public sector hospital in Soweto, South Africa was examined to gauge local capacity to deliver this procedure as an intervention for prevention of HIV acquisition. During the period from July 1998 to March 2006, approximately 360 procedures were performed per annum. Striking seasonal variations and the relatively few procedures performed may create challenges for program planning, if male circumcision is increased to a level required to have an impact on the incidence of HIV among this population. [ABSTRACT FROM AUTHOR]

Background: To explore adolescent HIV risk perception, HIV vaccine knowledge, willingness to participate in future HIV vaccine clinical trials, and the factors that influence willingness to participate among high school students in Soweto, South Africa, we recruited school-going youth through randomly selected local high schools. All pupils within the selected schools from whom parental consent and child assent could be obtained were eligible for participation. A self-administered, facilitated questionnaire was completed by all participants., Findings: Perception of adolescent HIV risk was high. Some misconceptions regarding vaccine research were common, particularly regarding placebo and potential eligibility criteria for prophylactic vaccine trials. Of 240 responses to the willingness item, 84 (35%) indicated they were "probably willing" and 126 (52.5%) that they were "definitely willing to participate". There were no significant differences in willingness by gender, age, school grade, or institution. Factors that were rated as "very important" in determining willingness included receiving current information about HIV research [n = 201 (88.9%)], doing something to honour people who have HIV or have died of AIDS [n = 168 (70.9%)], getting free counselling and testing [n = 167 (70.5)], that participants may receive some protection against HIV infection from the vaccine [n = 160 (70.2%)], and improving motivation to avoid risky behaviour [n = 134 (59%)]., Conclusion: Soweto school-going youth report high degrees of willingness to participate in HIV vaccine trials. This may be related to the high levels of adolescent HIV risk perception. Whether hypothetical willingness translates to participation will await data from adolescent HIV vaccine trials.