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Accurate and objective measurement of adherence is critical in microbicide trials. We compared two applicator tests: visual inspection of returned empty tenofovir gel applicators (VIREA) and ultraviolet light (UVL) assessment in terms of sensitivity and specificity, and for concordance. Sensitivity and specificity analysis of 24 control applicators (12 known-inserted and 12 sham-inserted) at 4-months after receipt was 75.0 and 66.7 % for VIREA and 83.3 and 91.7 % for UVL, respectively. After an additional 3 months of storage sensitivity and specificity was 100 and 58.3 % for VIREA and 100 and 66.7 % for UVL, respectively. In January 2015, 1316 empty applicators were returned as used by 115 participants enrolled at one site in a randomized controlled trial. Assessment outcomes showed 78.8 % agreement between the techniques. Methods concurred that 22.0 % of the returned empty applicators appeared unused. By UVL assessment, 40.0 % of returned empty applicators had no evidence of vaginal insertion, translating to a potential 28.0 % less product used as compared to that returned as used by women. UVL assessment may be considered a more accurate and less subjective measure of adherence as compared to VIREA. [ABSTRACT FROM AUTHOR]

Background The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide posttrial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial. Methods/design This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision. Discussion This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scaleup of microbicides within the public health system of South Africa. [ABSTRACT FROM AUTHOR]

Overestimating personal protection afforded by participation in a preventive trial, e.g. harboring a 'preventive misconception' (PM), raises theoretical ethical concerns about the adequacy of the informed consent process, behavioral disinhibition, and adherence to prevention interventions. Data from the CAPRISA 004 1 % tenofovir gel trial were utilized to empirically evaluate these concerns. We found it necessary to re-think the current definition of PM during evaluation to distinguish between true misconception and reasonable inferences of protection based on increased access to evidence-based prevention interventions and/or clinical care. There was a significant association between PM and decreased condom use ( p < 0.0001) and between PM and likelihood to present with an STI symptom ( p = 0.023). There was, however, limited evidence in support of PM representing a lack of meaningful informed consent, or to suggest that it impacts adherence. Moreover, considering current insufficiencies in female-initiated HIV prevention interventions, PM is perhaps of limited concern in microbicide trials. [ABSTRACT FROM AUTHOR]

Background. Diagnosis and treatment of sexually transmitted infections (STIs) is a public health priority, particularly in regions where the incidence of human immunodeficiency virus (HIV) infection is high. In most developing countries, STIs are managed syndromically. We assessed the adequacy of syndromic diagnosis of STIs, compared with laboratory diagnosis of STIs, and evaluated the association between STI diagnosis and the risk of HIV acquisition in a cohort of high-risk women.Methods. HIV-uninfected high-risk women (n = 242) were followed for 24 months. Symptoms of STIs were recorded, and laboratory diagnosis of common STI pathogens was conducted every 6 months. Forty-two cytokines were measured by Luminex in cervicovaginal lavage specimens at enrollment. Human immunodeficiency virus type 1 (HIV-1) infection was evaluated monthly.Results. Only 12.3% of women (25 of 204) who had a laboratory-diagnosed, discharge-causing STI had clinically evident discharge. Vaginal discharge was thus a poor predictor of laboratory-diagnosed STIs (sensitivity, 12.3%; specificity, 93.8%). Cervicovaginal cytokine concentrations did not differ between women with asymptomatic STIs and those with symptomatic STIs and were elevated in women with asymptomatic STIs, compared with women with no STIs or bacterial vaginosis. Although laboratory-diagnosed STIs were associated with increased risk of HIV infection (hazard ratio, 3.3 [95% confidence interval, 1.5–7.2)], clinical symptoms were not.Conclusions. Syndromic STI diagnosis dependent on vaginal discharge was poorly predictive of laboratory-diagnosed STI. Laboratory-diagnosed STIs were associated with increased susceptibility to HIV acquisition, while vaginal discharge was not. [ABSTRACT FROM AUTHOR]

Introduction: Young women are at disproportionate risk of HIV infection in South Africa. Understanding risk behaviors and factors associated with ability to negotiate safe sex and condom use is likely to be key in curbing the spread of HIV. Traditionally prevention efforts have focused on creating behavioral changes by increasing knowledge about HIV/AIDS. Methods: This was a cross-sectional analysis from a prospective observational cohort study of 245 women at a high-risk of HIV infection in KwaZulu-Natal, South Africa. Results: Participants demonstrated a high level of HIV/AIDS knowledge. Overall, 60.3% of participants reported condom use. Reported condom use at last sexual encounter varied slightly by partner type (57.0% with steady versus 64.4% with casual partners), and self-perceived ability to choose to use a condom was significantly lower with steady partners compared to casual partners (p<0.01). In multivariate analysis, women who had high school education were more likely to use condoms at their last sex encounter compared to those with only primary school education (RR of 1.36 (95% Confidence Interval (CI) 1.06-1.75) and 1.46 (95% CI 1.13-1.88) for grades 8-10 and 11-12, respectively). Those who used condoms as a contraceptive method were twice as likely to use condoms compared to women who did not report using them as a contraceptive method. Greater perceived ability to choose to use condoms was associated with higher self-reported condom use at last encounter, irrespective of partner type (RR = 2.65 (95% CI 2.15-32.5). Discussion: Self-perceived ability to use condoms, level of formal education and condom use as a contraceptive were all significantly associated with self-reported condom use at last sexual encounter. These findings suggest that that gender inequality and access to formal education, as opposed to lack of HIV/AIDS knowledge, prevent safer sexual practices in South Africa. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy (HAART) requires strict adherence to achieve optimal clinical and survival benefits. A study was done to explore the factors affecting HAART adherence among HIV positive adults by reviewing routinely collected patient information in the Centre for the AIDS Programme of Research in South Africa's (CAPRISA) AIDS Treatment Programme. Records of 688 patients enrolled between 2004 and 2006 were analysed. Patients were considered adherent if they had taken at least 95% of their prescribed drugs. Generalized estimating equations were used to analyse the data. The results showed that HAART adherence increased over time, however, the rate of increase differed by some of the socio-demographic and behavioural characteristics of the patients. For instance, HAART adherence increased in both urban and rural treatment sites over time, but the rate of increase was higher in the rural site. This helped identify sub-populations, such as the urban population, that required ongoing adherence counseling. [ABSTRACT FROM AUTHOR]

Background: Young women in sub-Saharan Africa bear a disproportionate burden of HIV infection compared to men but have limited options to reduce their HIV risk. Microbicides could fill an important HIV prevention gap for sexually active women who are unable to successfully negotiate mutual monogamy or condom use. Purpose: This paper describes the baseline sample characteristics in the CAPRISA 004 trial which assessed the safety and effectiveness of the vaginal microbicide, 1% tenofovir gel for HIV prevention in South Africa. Methods: This analysis assessed the baseline demographic, clinical and sexual behavior data of women screened and enrolled into the trial. The characteristics were summarized using descriptive summary measures; expressed as means and percent for categorical variables. Results: HIV prevalence at screening was 25.8% [95% Confidence Interval (CI):23.9-27.7). Of the 889 eligibly enrolled women who contributed follow-up data, rural participants recruited from a family planning (FP) clinic were younger, more likely to be living apart from their regular partner, reported lower coital frequency, had lower condom use (p < 0.001). In contrast, urban participants recruited from a sexually transmitted disease (STD) clinic reported higher numbers of lifetime sexual partners, new partners in the last 30 days and receiving money in exchange for sex (p < 0.001). [ABSTRACT FROM AUTHOR]

This study explores the influence of baseline factors on first-month adherence to highly active antiretroviral therapy (HAART) among adults. The study design involved a review of routinely collected patient information in the CAPRISA AIDS Treatment (CAT) programme, at a rural and an urban clinic in KwaZulu-Natal Province, South Africa. The records of 688 patients enrolled in the CAT programme between June 2004 and September 2006 were analysed. Adherence was calculated from pharmacy records (pill counts) and patients were considered adherent if they had taken at least 95% of their prescribed drugs. Logistic regression was used to analyse the data and account for confounding factors. During the first month of therapy, 79% of the patients were adherent to HAART. HAART adherence was negatively associated with a higher baseline CD4 count. Women had better adherence if they attended voluntarily testing and counselling or if they had taken an HIV test because they were unwell, while men had higher adherence if they were tested due to perceived risk of HIV infection. HAART adherence was positively associated with higher age among patients who possessed cell phones and among patients who provided a source of income in the urban setting, but not in the rural setting. Though long-term data from this cohort is required to fully evaluate the impact of non-adherence in the first month of treatment, this study identifies specific groups of patients at higher risk for whom adherence counselling should be targeted and tailored. For example, first-month HAART adherence can be improved by targeting patients initiated on treatment with a high CD4 count. [ABSTRACT FROM AUTHOR]

Objectives: To describe the baseline demographic data, clinical characteristics and HIV-incidence rates of a cohort at high risk for HIV infection in South Africa as well as the challenges experienced in establishing and maintaining the cohort. Methodology/Principle Findings: Between August 2004 and May 2005 a cohort of HIV-uninfected women was established for the CAPRISA 002 Acute Infection Study, a natural history study of HIV-1 subtype C infection. Volunteers were identified through peer-outreach. The cohort was followed monthly to determine HIV infection rates and clinical presentation of early HIV infection. Risk reduction counselling and male and female condoms were provided. After screening 775 individuals, a cohort of 245 uninfected high-risk women was established. HIV-prevalence at screening was 59.6% (95% CI: 55.9% to 62.8%) posing a challenge in accruing HIV-uninfected women. The majority of women (78.8%) were self-identified as sex-workers with a median of 2 clients per day. Most women (95%) reported more than one casual sexual partner in the previous 3 months (excluding clients) and 58.8% reported condom use in their last sexual encounter. Based on laboratory testing, 62.0% had a sexually transmitted infection at baseline. During 390 person-years of follow-up, 28 infections occurred yielding seroincidence rate of 7.2 (95% CI: 4.5 to 9.8) per 100 person-years. Despite the high mobility of this sex worker cohort retention rate after 2 years was 86.1%. High co-morbidity created challenges for ancillary care provision, both in terms of human and financial resources. Conclusions/Significance: Challenges experienced were high baseline HIV-prevalence, lower than anticipated HIVincidence and difficulties retaining participants. Despite challenges, we have successfully accrued this cohort of HIVuninfected women with favourable retention, enabling us to study the natural history of HIV-1 during acute HIV-infection. Our experiences provide lessons for others establishing similar cohorts, which will be key for advancing the vaccine and prevention research agenda in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Background: Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. Methods: We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. Results: From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3-15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5-13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0-13.8) at 6 months (n = 90), and 16.2 (IQR 9.6-20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels ⩽ 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported ⩽ 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8-94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95%CI, 1.27-119.71) and an HIVpositive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02-0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. Conclusion: This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting. [ABSTRACT FROM AUTHOR]

This study was conducted to identify predictors of mathematics achievement among grade 9 learners of a random sample of five township schools. A series of regression analyses were performed for boys and girls separately to obtain Cohen's (1992) effect size estimate (uniquely explained criterion variance expressed as a proportion of unexplained criterion variance) for various predictor variables. Cognitive predictors were verbal and non-verbal General Scholastic Aptitude Test scores. Non-cognitive variables included the hierarchical levels of self-concept: global (Rosenberg Self-Esteem Scale), and academic and mathematics self-concept (relevant scales of Brookover, Erickson and Joiner). Socio-economic predictors included home-related variables (parental education, parental occupation, family size) and school-related factors (class size, teacher's qualification, teacher's experience). Gender differences favouring boys were found. Non-verbal and verbal scholastic aptitude and teacher's general training correlated significantly with mathematics achievement for boys and girls, with non-verbal scholastic aptitude showing the highest correlation and effect size estimate for girls and teacher's general training occupying this position for boys. Teacher's mathematics training and class size showed correlations in excess of 0.35 for boys but not for girls. The negative correlation obtained for teacher's general training suggested that learners whose teachers held a three-year teaching diploma performed better in mathematics than did learners whose teachers held a degree and a teacher's diploma. [ABSTRACT FROM AUTHOR]

Background: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence.Methods/design: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15-49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15-35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84% power to detect a reduction of 30% in the HIV incidence rate between surveys.Discussion: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a "real world", non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance. [ABSTRACT FROM AUTHOR]

Background: The rates of death are high among patients with coinfection with tuberculosis and the human immunodeficiency virus (HIV). The optimal timing for the initiation of antiretroviral therapy in relation to tuberculosis therapy remains controversial. Methods: In an open-label, randomized, controlled trial in Durban, South Africa, we assigned 642 patients with both tuberculosis and HIV infection to start antiretroviral therapy either during tuberculosis therapy (in two integrated-therapy groups) or after the completion of such treatment (in one sequential-therapy group). The diagnosis of tuberculosis was based on a positive sputum smear for acid-fast bacilli. Only patients with HIV infection and a CD4+ cell count of less than 500 per cubic millimeter were included. All patients received standard tuberculosis therapy, prophylaxis with trimethoprim–sulfamethoxazole, and a once-daily antiretroviral regimen of didanosine, lamivudine, and efavirenz. The primary end point was death from any cause. Results: This analysis compares data from the sequential-therapy group and the combined integrated-therapy groups up to September 1, 2008, when the data and safety monitoring committee recommended that all patients receive integrated antiretroviral therapy. There was a reduction in the rate of death among the 429 patients in the combined integrated-therapy groups (5.4 deaths per 100 person-years, or 25 deaths), as compared with the 213 patients in the sequential-therapy group (12.1 per 100 person-years, or 27 deaths); a relative reduction of 56% (hazard ratio in the combined integrated-therapy groups, 0.44; 95% confidence interval, 0.25 to 0.79; P=0.003). Mortality was lower in the combined integrated-therapy groups in all CD4+ count strata. Rates of adverse events during follow-up were similar in the two study groups. Conclusions: The initiation of antiretroviral therapy during tuberculosis therapy significantly improved survival and provides further impetus for the integration of tuberculosis and HIV services. (ClinicalTrials.gov number, NCT00398996.) N Engl J Med 2010;362:697-706. [ABSTRACT FROM AUTHOR]

The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use. [ABSTRACT FROM AUTHOR]

Background: In several subgroups of South Africa, the percentage of HIV-positive individuals aware of their status falls well below the UNAIDS 90% target. This study examined the impact that home-based HIV testing services (HBHTS) had on knowledge of status in a hyperendemic area of South Africa., Methods: We analysed data from the second cross-sectional HIV Incidence Provincial Surveillance System survey (2015/2016), a representative sample (n = 10,236) of individuals aged 15-49 years. Participants completed a questionnaire, provided blood samples for laboratory testing (used to estimate HIV prevalence), and were offered HBHTS. The proportion of people living with HIV (n = 3870) made aware of their status through HBHTS was measured, and factors associated with HBHTS uptake were identified., Results: Knowledge of HIV-positive status at the time of the survey was 62.9% among men and 73.4% among women. Through HBHTS, the percentage of HIV-positive men and women who knew their status rose to 74.2% and 80.5%, respectively. The largest impact was observed among youth (15-24 years). Knowledge of status increased from 36.6% to 59.3% and from 50.8% to 64.8% among young men and women, respectively. In addition, 51.4% of those who had previously never tested received their first test. Key reasons for declining HBHTS among undiagnosed HIV-positive individuals included fear and self-report of an HIV-negative status., Conclusions: HBHTS was effective in increasing awareness of HIV-positive status, particularly among youth, men, and those who had never tested. HBHTS could have a marked impact on progress toward the UNAIDS 90-90-90 targets within these subgroups.

Background: In high HIV burden settings, maximising the coverage of prevention strategies is crucial to achieving epidemic control. However, little is known about the reach and effect of these strategies in some communities., Methods: We did a cross-sectional community survey in the adjacent Greater Edendale and Vulindlela areas in the uMgungundlovu district, KwaZulu-Natal, South Africa. Using a multistage cluster sampling method, we randomly selected enumeration areas, households, and individuals. One household member (aged 15-49 years) selected at random was invited for survey participation. After obtaining consent, questionnaires were administered to obtain sociodemographic, psychosocial, and behavioural information, and exposure to HIV prevention and treatment programmes. Clinical samples were collected for laboratory measurements. Statistical analyses were done accounting for multilevel sampling and weighted to represent the population. A multivariable logistic regression model assessed factors associated with HIV infection., Findings: Between June 11, 2014, and June 22, 2015, we enrolled 9812 individuals. The population-weighted HIV prevalence was 36·3% (95% CI 34·8-37·8, 3969 of 9812); 44·1% (42·3-45·9, 2955 of 6265) in women and 28·0% (25·9-30·1, 1014 of 3547) in men (p<0·0001). HIV prevalence in women aged 15-24 years was 22·3% (20·2-24·4, 567 of 2224) compared with 7·6% (6·0-9·3, 124 of 1472; p<0·0001) in men of the same age. Prevalence peaked at 66·4% (61·7-71·2, 517 of 760) in women aged 35-39 years and 59·6% (53·0-66·3, 183 of 320) in men aged 40-44 years. Consistent condom use in the last 12 months was 26·5% (24·1-28·8, 593 of 2356) in men and 22·7% (20·9-24·4, 994 of 4350) in women (p=0·0033); 35·7% (33·4-37·9, 1695 of 5447) of women's male partners and 31·9% (29·5-34·3, 1102 of 3547) of men were medically circumcised (p<0·0001), and 45·6% (42·9-48·2, 1251 of 2955) of women and 36·7% (32·3-41·2, 341 of 1014) of men reported antiretroviral therapy (ART) use (p=0·0003). HIV viral suppression was achieved in 54·8% (52·0-57·5, 1574 of 2955) of women and 41·9% (37·1-46·7, 401 of 1014) of men (p<0·0001), and 87·2% (84·6-89·8, 1086 of 1251) of women and 83·9% (78·5-89·3, 284 of 341; p=0·3670) of men on ART. Age, incomplete secondary schooling, being single, having more than one lifetime sex partner (women), sexually transmitted infections, and not being medically circumcised were associated with HIV-positive status., Interpretation: The HIV burden in specific age groups, the suboptimal differential coverage, and uptake of HIV prevention strategies justifies a location-based approach to surveillance with finer disaggregation by age and sex. Intensified and customised approaches to seek, identify, and link individuals to HIV services are crucial to achieving epidemic control in this community., Funding: The President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: We assessed whether women who acquired HIV during tenofovir gel prophylaxis trials can be safely and effectively treated with tenofovir-containing antiretroviral therapy (ART)., Methods: Between May 2011 and October 2014, HIV seroconvertors from two tenofovir gel trials were recruited when eligible for ART (CD4 + T-cell count <350 cells/μl, pregnancy or AIDS-defining illness). Women were randomized to tenofovir-containing (tenofovir + lamivudine/emtricitabine + efavirenz) or tenofovir-sparing (zidovudine + lamivudine/emtricitabine + efavirenz) antiretroviral treatment regimens. The proportion with virological suppression, adverse events and drug switches were compared., Results: Fifty-nine women were enrolled and followed-up for median 18 months (IQR 6-24). Twenty-nine women (7 tenofovir gel exposed, 22 tenofovir gel unexposed) were randomized to a tenofovir-containing and 30 (9 tenofovir gel exposed, 21 tenofovir gel unexposed) to a tenofovir-sparing regimen. Median baseline CD4 + T-cell count and viral load (VL) were 345 cells/μl (IQR 280-423) and 4.5 log copies/ml (sd 0.79), and did not differ by ART assignment. Overall VL suppression rates were 88.0% and 78.3% at 6 months (P=0.454) and 85.7% and 79.0% at 12 months (P=0.689) in women on the tenofovir-containing and tenofovir-sparing regimens, respectively. Toxicity-related drug switches were more frequent in women on the tenofovir-sparing than tenofovir-containing regimen (36.7% versus 0.0%, P<0.001)., Conclusions: Preliminary data show that tenofovir-containing ART was effective and more tolerable in HIV seroconvertors from tenofovir gel prophylaxis trials and may be considered for use in women with prior tenofovir gel exposure. Clinical trials.gov NCT01387022.

Objective: Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV coinfected patients. In patients with CD4 counts <50 cells per cubic millimeter, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost-effectiveness of starting ART at various time points during TB treatment in patients with CD4 counts ≥50 cells per cubic millimeter., Methods: In the SAPiT trial, 642 HIV-TB coinfected patients were randomized to 3 arms: receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct health care costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes., Results: For patients with CD4 count ≥50 cells per cubic millimeter, median monthly variable costs per patient were US $116, US $113, and US $102 in Arm-1, Arm-2 and Arm-3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2, and 19 deaths in 172 patients in Arm-3. Although the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was US $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive., Conclusions: Initiation of ART after the completion of the intensive phase of TB treatment is cost-effective for patients with CD4 counts ≥50 cells per cubic millimeter.

Background: Women in Africa, especially young women, have very high human immunodeficiency virus (HIV) incidence rates that cannot be fully explained by behavioral risks. We investigated whether genital inflammation influenced HIV acquisition in this group., Methods: Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (interleukin [IL]-1α, IL-1β, IL-6, tumor necrosis factor-α, IL-8, interferon-γ inducible protein-10 [IP-10], monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1α, MIP-1β), hematopoietic IL-7, and granulocyte macrophage colony-stimulating factor, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconverters and 58 matched uninfected controls and in plasma from a subset of 107 of these women from the Centre for the AIDS Programme of Research in South Africa 004 tenofovir gel trial., Results: HIV seroconversion was associated with raised genital inflammatory cytokines (including chemokines MIP-1α, MIP-1β, and IP-10). The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised (odds ratio, 3.2; 95% confidence interval, 1.3-7.9; P = .014). Genital cytokine concentrations were persistently raised (for about 1 year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections and systemic cytokines., Conclusions: Elevated genital concentrations of HIV target cell-recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine if urinary lipoarabinomannan (LAM) may serve as a biomarker to monitor antituberculosis (TB) therapy response, and whether LAM results before and after treatment are predictive of patient outcomes., Design: Prospective cohort., Setting: Outpatient referral clinic and tertiary hospital in South Africa., Participants: Adults (≥18 years) with ≥2 TB-related symptoms (cough, fever, weight loss, night sweats) for ≥2 weeks being initiated on anti-TB therapy., Interventions: On enrolment, we obtained urine and nebulised sputum specimens, offered HIV testing and started participants on anti-TB therapy for ≥6 months. We collected urine samples after the 2-month intensive treatment phase and at the completion of anti-TB therapy. Positive LAM results were graded from 1 (low) to 5 (high). Participants were followed for >3 years., Outcome Measures: The primary outcome was change in urine LAM results during anti-TB therapy. The secondary outcome was all-cause mortality., Results: Among 90 participants, 57 (63%) had culture-confirmed pulmonary TB. Among the 88 participants tested, 82 (93%) were HIV-infected with median CD4 168/mm(3) (IQR 89-256/mm(3)). During anti-TB therapy, the percentage of LAM-positive participants decreased from baseline to 2 months (32% to 16%), and from baseline to 6-months (32% to 10%) (p values <0.005). In multivariate longitudinal analyses, urine LAM positivity and grade decreased among those with culture-confirmed pulmonary TB (p<0.0001), and had no change in sputum culture-negative participants. At the 2-month visit, participants with positive laboratory-based LAM or rapid LAM with ≥2+ grade had a significantly greater risk of mortality. In analyses adjusted for age, sex, baseline Karnofsky score and HIV status, participants with a rapid LAM ≥2+ grade after 2 months of anti-TB therapy had a 5.6-fold (95% CI 1.2 to 25.2) greater risk of mortality., Conclusions: Rapid urine LAM testing may be a valuable tool to monitor anti-TB therapy response and to assess prognosis of patients being treated for pulmonary TB in HIV-endemic regions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Precise knowledge of the prevalence and spectrum of skin diseases in a population allows for effective planning for provision of dermatology services and distribution of resources. There are no published data on the epidemiology of skin disorders in Durban, KwaZulu-Natal., Objective: We investigated the prevalence of skin diseases in black African patients attending a predominantly black private healthcare facility and profiled the patients., Methods: Clinical charts of all black African patients seen between January 2003 and December 2010 in a private practice in Durban were reviewed. The diseases seen were described and the prevalence calculated., Results: A total of 6664 patient charts were reviewed. The five most common conditions were acne, eczemas, dyschromias, infections, and hair disorders. These data agree with reports from other parts of the world., Limitations: Selection bias was presented by a single private practice, thus data may not be fully representative of our population., Conclusion: Acne, eczemas, dyschromias, infections, and hair disorders are, in that order, the five most common disorders encountered., (© 2014 The International Society of Dermatology.)

Objective: Adolescents in southern African high schools are a key population for HIV prevention interventions. We report on the prevalence of HIV, HSV-2 and pregnancy as indicators of high-risk sexual behaviour among high school students in rural KwaZulu-Natal., Design: Bio-behavioural cross-sectional survey., Methods: Students completed a self-administered structured, standardised demographic and sexual behavioural questionnaire. Dried blood spot specimens were collected for HIV and HSV-2 testing. Urine specimens were used for pregnancy testing in female students., Results: A total of 2675 (1423 females, 1252 males) consenting students were enrolled from 14 high schools between September and November 2010. The median age of students was 16 years (IQR 15-18). HIV prevalence was 1.4% (95% CI 0.9 to 1.9) in males and 6.4% (95% CI 4.6 to 8.3) in females (p<0.001). HSV-2 prevalence was 2.6% (95% CI 1.6 to 3.7) in males and 10.7% (95% CI 8.8 to 12.6) in females (p<0.001). Pregnancy prevalence was 3.6% (95% CI 2.6 to 4.5). Risk factors for prevalent HIV infection in female students included being over 18 years of age (adjusted OR (aOR)=2.67, 95% CI 1.67 to 4.27; p<0.001), prevalent HSV-2 infection (aOR=4.35, 95% CI 2.61 to 7.24; p<0.001), previous pregnancy (aOR=1.66, 95% CI 1.10 to 2.51; p=0.016) and experience of two or more deaths in the household in the previous year (aOR=1.97, 95% CI 1.13 to 3.44; p=0.016)., Conclusions: The high prevalence of HIV, HSV-2 and pregnancy underscore the need for school-based sexual and reproductive health services, and provide further impetus for the inclusion of adolescents in behavioural and biomedical trials with HIV incidence endpoints., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Anaemia is a common clinical finding in HIV infected women and has been associated with advanced disease. The use of antiretroviral drugs such as Zidovudine (ZDV) either for prevention of mother to child transmission (MTCT) of HIV or used in combination with other antiretrovirals have been implicated in the development or increased severity of anaemia. We report the prevalence, type, severity and incidence of anaemia in a cohort of HIV infected women who initiated antiretroviral prophylaxis or treatment during pregnancy., Methods and Materials: This is a retrospective cohort data analysis of 408 HIV infected pregnant women who participated in a breastfeeding intervention study (HPTN 046 Study, ClinicalTrials.gov NCT 00074412) in South Africa. Women initiated zidovudine prophylaxis for PMTCT or triple antiretroviral treatment in pregnancy according to the standard of care. Laboratory and clinical data in pregnancy, <72 hours and 2 weeks postdelivery were extracted from the main database and analysed., Results: The mean Hb concentration was 10.6 g/dL at baseline and 262/408 (64.2%) women were diagnosed with anaemia (Hb<11 g/dL) in pregnancy, 48/146 (32.9%) subsequently developed anaemia intrapartum or postpartum and 89/310 (28.7%) of all cases of anaemia remained unresolved by 2 weeks postdelivery. In a univariate analysis, CD4 count and gravidity were significant risk factors for anaemia in pregnancy, RR 1.41; 1.23-1.61 (p<0.001) and 1.10; 1.01-1.18 (p = 0.02) respectively. After adjusting for antiretroviral regimen, age and gravidity in a multivariable analysis, only the CD4 count remains a significant risk factor for anaemia in pregnancy and postdelivery., Conclusion: In conclusion, anaemia was most common among women in the advanced stage of HIV infection (CD4<200 cells/mm3). There was no evidence of an association between ZDV or triple ARVs and anaemia.

Background: Skin-lightening products are commonly used by black communities in South Africa and worldwide. This practice has deep historical and cultural roots and is associated with adverse cutaneous effects., Methods: A cross-sectional survey of 579 African and Indian women aged 18-70 years was conducted in two large public hospitals in Durban, South Africa., Results: There were 292 Africans and 287 Indians included in the survey sample. Of these 32.3% had used skin-lightening products (60% of Africans and 40% of Indians). Most of those who had used skin lighteners (85 of Africans and 76% of Indians) claimed awareness of the adverse effects of the products, although this did not appear to inform knowledge of the product, how it was used, nor the decision to use the product. Most users (90%) expressed satisfaction with results achieved but 32% reported adverse events., Conclusion: Skin-lightening products are used by a third of African and Indian women in South Africa Cultural and historical perceptions equating a fairer skin with social advantage are pervasive and strongly reinforced by the media. There is a poor understanding of the risks associated with the use of these products. Public education campaigns are required to teach consumers about these risks and the importance of concomitant use of sunscreens with these products., (© 2014 Wiley Periodicals, Inc.)

High adherence is key to microbicide effectiveness. Here we provide a description of adherence interventions and the adherence rates achieved in the CAPRISA 004 Tenofovir gel trial. Adherence support for the before-and-after dosing strategy (BAT 24) was provided at enrolment and at each monthly study visit. This initially comprised individual counselling and was replaced midway by a structured theory-based adherence support program (ASP) based on motivational interviewing. The 889 women were followed for an average of 18 months and attended a total of 17,031 monthly visits. On average women reported five sex acts and returned 5.9 empty applicators per month. The adherence rate based on applicator count in relation to all reported sex acts was 72.2 % compared to the 82.0 % self-reported adherence during the last sex act. Adherence support activities, which achieve levels of adherence similar to or better than those achieved by the CAPRISA 004 ASP, will be critical to the success of future microbicide trials.

Background: Tenofovir gel, used vaginally before and after coitus, reduced women's acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters., Methods: In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated., Results: Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group., Conclusions: No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile.

Background: Although recent World Health Organization (WHO) guidelines recommend withdrawing stavudine (d4T) from first-line antiretroviral therapy (ART), it remains commonly used in resource-limited settings. In 2006, WHO recommended decreasing the dose of d4T from 40 mg to 30 mg to mitigate toxicities. We compared the incidence and severity of peripheral neuropathy by d4T dose in a retrospective cohort study., Methods: Patients' charts from an ART-naive population at a rural clinic in KwaZulu-Natal, South Africa, were retrospectively reviewed for signs and symptoms of incident peripheral neuropathy and were graded for severity using the DAIDS scale. Patients enrolled prior to the WHO guideline change were included in the study if they were on d4T 40 mg for ≥6 months. After the guideline change all patients were initiated on d4T 30 mg., Results: A total of 475 patients were analysed, including 235 in the 40 mg cohort (152.7 person-years [py]) and 240 in the 30 mg cohort (244.7 py). Incidence of peripheral neuropathy was 90.4/100 py (95% CI 75.9, 106.8) in the 40 mg cohort versus 40.5/100 py (95% CI 32.9, 49.3) in the 30 mg group (incidence rate ratio 0.45; P<0.0001). There was no difference in proportion of severe peripheral neuropathy cases (grade 3/4) between the cohorts: 8.3% in the 40 mg group and 8.9% in the 30 mg group (P=1.0). In a multivariate analysis, risk of peripheral neuropathy was associated with increasing age (hazard ratio [HR] 1.65, 95% CI 1.24, 2.19), 40 mg dose (HR 2.1, 95% CI 1.61, 2.74) and concurrent tuberculosis therapy (HR 1.41, 95% CI 1.06, 1.87)., Conclusions: Incidence of peripheral neuropathy in the 40 mg cohort was extremely high and, although lower, the rate in the 30 mg cohort was nonetheless unacceptably high.

Background: The high prevalence of anaemia and the increased morbidity and mortality associated with anaemia during AIDS has been well described yet there has been little information about anaemia and changes in haemoglobin levels during acute and early HIV-1 infection., Methods: HIV-negative women (n = 245) were enrolled into an observational cohort as part of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) Acute Infection Study. Acute infection was diagnosed following a positive HIV RNA PCR in the absence of antibodies, or detection of HIV-1 antibodies within 3 months of a previously negative antibody test. Haemotologic parameters were assessed before infection and at regular intervals in the first twelve months of HIV infection., Results: Fifty-seven participants with acute HIV infection were identified at a median of 14.5 days post-infection (range 10-81) and were enrolled in the CAPRISA Acute Infection cohort at a median of 41 days post-infection (range 15-104). Mean haemoglobin prior to HIV-1 infection was 12.7 g/dL, with a mean decline of 0.46 g/dL following infection. The prevalence of anaemia increased from 25.0% prior to HIV-1 infection to 52.6% at 3 months post-infection, 61.1% at 6 months post-infection, and 51.4% at 12 months post-infection., Conclusions: Haematologic derangements and anaemia with a trend towards iron deficiency are common with acute HIV-1 subtype C infection in this small cohort. The negative impact of anaemia concurrent with established HIV infection upon morbidity and mortality has been well documented but the prognostic potential and long-term effects of anaemia during acute HIV-1 infection remain unknown.