Women's knowledge and perception of male circumcision before and after its roll-out in the South African township of Orange Farm from community-based cross-sectional surveys.

The roll-out of medical male circumcision (MC) is progressing in Southern and Eastern Africa. Little is known about the effect of this roll-out on women. The objective of this study was to assess the knowledge and perceptions of women regarding MC in a setting before and after the roll-out. This study was conducted in the South African township of Orange Farm where MC prevalence among men increased from 17% to 53% in the period 2008-2010. Data from three community-based cross sectional surveys conducted in 2007, 2010 and 2012 among 1258, 1197 and 2583 adult women, respectively were studied. In 2012, among 2583 women, 73.7% reported a preference for circumcised partners, and 87.9% knew that circumcised men could become infected with HIV. A total of 95.8% preferred to have their male children circumcised. These three proportions increased significantly during the roll-out. In 2007, the corresponding values were 64.4%, 82.9% and 80.4%, respectively. Among 2581 women having had sexual intercourse with circumcised and uncircumcised men, a majority (55.8%, 1440/2581) agreed that it was easier for a circumcised man to use a condom, 20.5% (530/2581) disagreed; and 23.07 (611/2581) did not know. However, some women incorrectly stated that they were fully (32/2579; 1.2%; 95%CI: 0.9% to 1.7%) or partially (233/2579; 9.0%; 95%CI: 8.0% to 10.2%) protected when having unprotected sex with a circumcised HIV-positive partner. This study shows that the favorable perception of women and relatively correct knowledge regarding VMMC had increased during the roll-out of VMMC. When possible, women should participate in the promotion of VMMC although further effort should be made to improve their knowledge.

Obtaining a male circumcision prevalence rate of 80% among adults in a short time: An observational prospective intervention study in the Orange Farm township of South Africa.

World Health Organization recommends a target for the male circumcision prevalence rate of 80%. This rate will have a substantial impact on the human immunodeficiency virus-acquired immunodeficiency syndrome epidemic in Eastern and Southern Africa. The objective of the study was to assess whether an innovative intervention can lead to an increased voluntary male medical circumcision (VMMC) uptake among adults in a short time. This prospective observational study of a demand generation intervention was conducted in the township of Orange Farm (South Africa) in August to November 2015. In this community male circumcision prevalence rate among adults was stable between 2010 and 2015 at 55% and 57%, despite regular VMMC campaigns at community level and the presence of a VMMC clinic that offered free VMMC. The intervention took place in a random sample of 981 households where 522 men aged 18 to 49 years accepted to participate in the study. Among the 226 uncircumcised men, 212 accepted to be enrolled in the intervention study. A personal male circumcision adviser trained in interpersonal communication skills was assigned to each uncircumcised participant. The male circumcision advisers were trained to explain the risks and benefits of VMMC, and to discuss 24 possible reasons given by men for not being circumcised. Participants were then followed for 9 weeks. Each participant had a maximum of 3 motivational interviews at home. Participants who decided to be circumcised received financial compensation for their time equivalent to 2.5 days of work at the minimum South African salary rate. Among the 212 uncircumcised men enrolled in the intervention, 69.8% (148/212; 95% confidence interval [CI]; 63.4%-75.7%) agreed to be circumcised, which defines the uptake of the intervention. The male circumcision prevalence rate of the sample increased from 56.7% (296/522) to 81.4% (425/522; 77.9%-84.6%), P < 0.001, corresponding to a relative increase of 43.6% (95% CI: 35.4%-53.7%). The reported reasons for accepting circumcision were motivational interviews with the male circumcision adviser (83.1%), and time compensation (39.4%).Increased uptake of VMMC uptake can be obtained in a short time among adult males but requires an intense intervention centered on uncircumcised men at an individual level and time compensation.

Sequential Cross-Sectional Surveys in Orange Farm, a Township of South Africa, Revealed a Constant Low Voluntary Medical Male Circumcision Uptake among Adults despite Demand Creation Campaigns and High Acceptability.

BACKGROUND: WHO recommends a male circumcision (MC) prevalence rate higher than 80% to have a substantial impact on the HIV-AIDS epidemic in Eastern and Southern Africa. Orange Farm, a township in South Africa, has a free-for-service voluntary medical male circumcision (VMMC) clinic in operation since 2008. Following an intense campaign from 2008 to 2010, MC prevalence rate increased to 55.4% (ANRS-12126). Ongoing and past VMMC campaigns focused on youths, through school talks, and adults at a community level. The main objective of the study was to assess the change in MC prevalence rate among adults aged 18-19 and 18-49 years in the past 5 years. METHODS: A cross-sectional survey (ANRS-12285) was conducted among a random sample of 522 adult men in 2015. MC status and characteristics of participants were collected through a genital examination and a face-to-face questionnaire. RESULTS: MC prevalence rate among young adult men aged 18-19 years increased markedly from 61.2% (95%CI: 57.4% to 65.0%) in 2010 to 87.5% (76.0% to 94.6%) in 2015 (p<0.001). In the same period, among men aged 18-49 years, MC prevalence rate varied slightly from 55.4% (53.6% to 57.1%) to 56.7% (52.4% to 60.9%). In 2015, 84.9% (79.2% to 89.5%) of uncircumcised adult men reported that they were willing to be circumcised. However, we estimated that only 4.6% (11/237; 2.5% to 7.9%) of the uncircumcised men underwent circumcision in 2015, despite 117/185 (63.2%; 95%CI: 56.1% to 69.9%) who reported that they were definitely willing to become circumcised. CONCLUSIONS: In Orange Farm, VMMC campaigns were successful among the youth and led to a sufficiently high MC prevalence rate to have a substantial impact in the future on the HIV-AIDS epidemic. However, despite high acceptability and a free VMMC service, VMMC campaigns since 2010 have failed to increase MC prevalence rate among adults to above 80%. These campaigns should be revisited.

Level of viral suppression and the cascade of HIV care in a South African semi-urban setting in 2012.

OBJECTIVE: In 2012, 7 years after the introduction of antiretroviral treatment (ART) in the South African township of Orange Farm, we measured the proportion of HIV-positive people who were virally suppressed, especially among high-risk groups (women 18-29 years and men 25-34 years). DESIGN: A community-based cross-sectional representative survey was conducted among 3293 men and 3473 women. METHODS: Study procedures included a face-to-face interview and collection of blood samples that were tested for HIV, 11 antiretroviral drugs and HIV-viral load. RESULTS: HIV prevalence was 17.0% [95% confidence interval: 15.7-18.3%] among men and 30.1% [28.5-31.6%] among women. Overall, 59.1% [57.4-60.8%] of men and 79.5% [78.2-80.9%] of women had previously been tested for HIV. When controlling for age, circumcised men were more likely to have been tested compared with uncircumcised men (66.1 vs 53.6%; P < 0.001). Among HIV+, 21.0% [17.7-24.6%] of men and 30.5% [27.7-33.3%] of women tested positive for one or more antiretroviral drugs. Using basic calculations, we estimated that, between 2005 and 2012, ART programs prevented between 46 and 63% of AIDS-related deaths in the community. Among antiretroviral-positive, 91.9% [88.7-94.3%] had viral suppression (viral load <400 copies/ml). The proportion of viral suppression among HIV+ was 27.0% [24.3-29.9%] among women and 17.5% [14.4-20.9%] among men. These proportions were lower among the high-risk groups: 15.6% [12.1-19.7%] among women and 8.4% [5.0-13.1%] among men. CONCLUSION: In Orange Farm, between 2005 and 2012, ART programs were suboptimal and, among those living with HIV, the proportion with viral suppression was still low, especially among the young age groups. However, our study showed that, in reality, antiretroviral drugs are highly effective in viral suppression at an individual level.

Influence of trial duration on the bias of the estimated treatment effect in clinical trials when individual heterogeneity is ignored.

In randomized clinical trials where the times to event of two treatment groups are compared under a proportional hazards assumption, it has been established that omitting prognostic factors from the model entails an underestimation of the hazards ratio. Heterogeneity due to unobserved covariates in cancer patient populations is a concern since genomic investigations have revealed molecular and clinical heterogeneity in these populations. In HIV prevention trials, heterogeneity is unavoidable and has been shown to decrease the treatment effect over time. This article assesses the influence of trial duration on the bias of the estimated hazards ratio resulting from omitting covariates from the Cox analysis. The true model is defined by including an unobserved random frailty term in the individual hazard that reflects the omitted covariate. Three frailty distributions are investigated: gamma, log-normal, and binary, and the asymptotic bias of the hazards ratio estimator is calculated. We show that the attenuation of the treatment effect resulting from unobserved heterogeneity strongly increases with trial duration, especially for continuous frailties that are likely to reflect omitted covariates, as they are often encountered in practice. The possibility of interpreting the long-term decrease in treatment effects as a bias induced by heterogeneity and trial duration is illustrated by a trial in oncology where adjuvant chemotherapy in stage 1B NSCLC was investigated.

Mixture models for calibrating the BED for HIV incidence testing.

A number of antibody biomarkers have been developed to distinguish between recent and established Human Immunodeficiency Virus (HIV) infection and used for HIV incidence estimation from cross-sectional specimens. In general, a cut-off value is specified, and estimates of the following parameters are needed: (i) the mean time interval .w/ between seroconversion and reaching that cut-off; (ii) the probability of correctly identifying individuals who became infected in the last w years (sensitivity); and (iii) the probability of correctly identifying individuals who have been infected for more than w years (specificity). We develop two statistical methods to study the distribution of a biomarker and derive a formula for estimating HIV incidence from a cross-sectional survey. Both methods allow handling interval censored data and basically consist of using a generalized mixture model to model the growth of the biomarker as a function of time since infection. The first uses data from all followed-up individuals and allows incidence estimation in the cohort, whereas the second only uses data from seroconverters. We illustrate our methods using repeated measures of the IgG capture BED enzyme immunoassay. Estimates of calibration parameters, that is, mean window period, mean recency period, sensitivity, and specificities obtained from both models are comparable. The formula derived for incidence estimation gives the maximum likelihood estimate of incidence which, for a given window period, depends only on sensitivity and specificity. The optimal choice of the window period is discussed. Numerical simulations suggest that data from seroconverters can provide reasonable estimates of the calibration parameters.

Association of the ANRS-12126 male circumcision project with HIV levels among men in a South African township: evaluation of effectiveness using cross-sectional surveys.

BACKGROUND: Randomized controlled trials have shown that voluntary medical male circumcision (VMMC) reduces HIV infection by 50% to 60% in sub-Saharan African populations; however, little is known about the population-level effect of adult male circumcision (MC) as an HIV prevention method. We assessed the effectiveness of VMMC roll-out on the levels of HIV in the South African township of Orange Farm where the first randomized controlled trial (RCT) to test the effect of VMMC on HIV acquisition was conducted in 2002-2005. METHODS AND FINDINGS: The Bophelo Pele project is a community-based campaign against HIV, which includes the roll-out of free VMMC. A baseline cross-sectional biomedical survey was conducted in 2007-2008 among a random sample of 1,998 men aged 15 to 49 (survey response rate 80.7%). In 2010-2011, we conducted a follow-up random survey among 3,338 men aged 15 to 49 (survey response rate 79.6%) to evaluate the project. Participants were interviewed, blood samples were collected and tested for HIV and recent HIV infection (using the BED HIV incidence assay), and MC status was assessed through a clinical examination. Data were analyzed using multivariate and propensity statistical methods. Owing to the VMMCs performed in the context of the RCT and the Bophelo Pele project, the prevalence rate of adult MC increased from 0.12 (95% CI 0.10-0.14) to 0.53 (95% CI 0.51-0.55). Without these VMMCs, the HIV prevalence rate in 2010-2011 would have been 19% (95% CI 12%-26%) higher (0.147 instead of 0.123). When comparing circumcised and uncircumcised men, no association of MC status with sexual behavior was detected. Among circumcised and uncircumcised men, the proportion consistently using condoms with non-spousal partners in the past 12 months was 44.0% (95% CI 41.7%-46.5%) versus 45.4% (95% CI 42.2%-48.6%) with weighted prevalence rate ratio (wPRR) = 0.94 (95% CI 0.85-1.03). The proportion having two or more non-spousal partners was 50.4% (95% CI 47.9%-52.9%) versus 44.2% (95% CI 41.3%-46.9%) with wPRR = 1.03 (95% CI 0.95-1.10). We found a reduction of BED-estimated HIV incidence rate ranging from 57% (95% CI 29%-76%) to 61% (95% CI 14%-83%) among circumcised men in comparison with uncircumcised men. CONCLUSIONS: Findings suggest that the roll-out of VMMC in Orange Farm is associated with a significant reduction of HIV levels in the community. The main limitation of the study is that it was not randomized and cannot prove a causal association. The roll-out of VMMC among adults in sub-Saharan Africa should be an international priority and needs to be accelerated to effectively combat the spread of HIV. Please see later in the article for the Editors' Summary.

Association of genital human papillomavirus infection with HIV acquisition: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and a meta-analysis of epidemiological studies investigating the association of genital human papillomavirus (HPV) infection and HIV acquisition. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Scientific databases and conference abstracts were systematically searched to identify all relevant studies published up to 31 January 2012. Search terms included 'HIV', 'HPV', 'humanpapillomavirus' and 'papillomaviridae' as keywords or text, in the title or abstract. METHODS: To be eligible for inclusion, a study had to be conducted among humans, report data on HIV incidence, and assess genital HPV infection. Summary ORs and 95% CIs were estimated from the extracted data using random-effect meta-analysis. Subgroup analyses were conducted for high-risk (HR) and low-risk(LR) HPV oncogenic risk groups. Between-study heterogeneity and publication bias were assessed. RESULTS: Of 2601 identified abstracts, six observational studies, comprising 6567 participants were retained for the systematic review and the meta-analysis. HIV acquisition was significantly associated with HPV infection (summary OR=1.96; 95% CI 1.55 to 2.49). HIV incident infection was significantly associated with HR-HPV in five of six studies and with LR-HPV in two out of five. The association was significant for HR-HPV(summary OR=1.92; 95% CI 1.49 to 2.46) and borderline for LR-HPV. No between-study heterogeneity was detected. There was a borderline indication of publication bias. CONCLUSIONS: Further research is needed to elucidate the biological mechanisms involved, and assess the effect of HPV vaccination on HIV acquisition, using vaccines with broad coverage of HPV genotypes. Such research could have important public health implications for HIV prevention.

Prospective assessment of incidence of Tako-Tsubo cardiomyopathy in a very large urban agglomeration.

BACKGROUND: Tako-Tsubo cardiomyopathy (TTC) is a recently described medical entity and the incidence of TTC in a global population is still uncertain. We sought to prospectively assess the incidence of TTC in a large urban area. METHODS AND RESULTS: We included all consecutive patients referred for coronary angiography in three hospitals located in Paris and its suburbs. We prospectively estimated the percentage of TTC among patients referred for coronary angiography and extrapolated the number of cases of TTC in the greater Paris area (11,598,866 inhabitants) according to the CARDIO-ARHIF registry (government agency). Among 2547 patients (2972 coronary angiographies) including 815 acute coronary syndromes, 20 patients presented with TTC (19 women, mean age 66 ± 13 years). The percentage of TTC among suspected acute coronary syndromes was 2.5% (8.2% in women versus 0.2% in men, p<0.001). In the CARDIO-ARHIF registry, we individualized 51,403 coronary angiographies performed in all catheterization laboratories in one year (13,820 women and 10,246 women ≥ 60 years). In this region, the yearly number of TTC cases is estimated to be 346 (95% CI: 216-520). The annual incidence of TTC is estimated to be 29.8 per 1,000,000 inhabitants (95% CI: 18.6-44.9), 48.2 per 1,000,000 inhabitants (95% CI: 29.7-73.0) among women and 187.4 per 1,000,000 inhabitants (95% CI: 103.3-307.2) among women ≥ 60 years. CONCLUSIONS: Within a large urban agglomeration, the incidence of TTC is high in women ≥ 60 years. The current rate of this recently described cardiomyopathy has been underestimated in previous retrospective studies and will probably rise with the increase of life expectancy.

Adult male circumcision as an intervention against HIV: an operational study of uptake in a South African community (ANRS 12126).

BACKGROUND: To evaluate the knowledge, attitudes and beliefs about adult male circumcision (AMC), assess the association of AMC with HIV incidence and prevalence, and estimate AMC uptake in a Southern African community. METHODS: A cross-sectional biomedical survey (ANRS-12126) conducted in 2007-2008 among a random sample of 1198 men aged 15 to 49 from Orange Farm (South Africa). Face-to-face interviews were conducted by structured questionnaire. Recent HIV infections were evaluated using the BED incidence assay. Circumcision status was self-reported and clinically assessed. Adjusted HIV incidence rate ratios (aIRR) and prevalence ratios (aPR) were calculated using Poisson regression. RESULTS: The response rate was 73.9%. Most respondents agreed that circumcised men could become HIV infected and needed to use condoms, although 19.3% (95%CI: 17.1% to 21.6%) asserted that AMC protected fully against HIV. Among self-reported circumcised men, 44.9% (95%CI: 39.6% to 50.3%) had intact foreskins. Men without foreskins had lower HIV incidence and prevalence than men with foreskins (aIRR = 0.35; 95%CI: 0.14 to 0.88; aPR = 0.45, 95%CI: 0.26 to 0.79). No significant difference was found between self-reported circumcised men with foreskins and other uncircumcised men. Intention to undergo AMC was associated with ethnic group and partner and family support of AMC. Uptake of AMC was 58.8% (95%CI: 55.4% to 62.0%). CONCLUSIONS: AMC uptake in this community is high but communication and counseling should emphasize what clinical AMC is and its effect on HIV acquisition. These findings suggest that AMC roll-out is promising but requires careful implementation strategies to be successful against the African HIV epidemic.

Partial inactivation of CCR5- and CXCR4- tropic HIV-1 by human urine.

Human urine has been poorly investigated with regard to infection with human immunodeficiency virus (HIV). Here, we have studied the anti-infective functional properties of human urine against HIV. The effect of fresh urine pools on CCR5- and CXCR4-tropic HIV-1 was evaluated by using four in vitro mucosal models: reduction of infectivity of urine-treated HIV-1 particles, HIV-1 attachment to immature monocyte-derived dendritic cells (iMDDC), transfer of HIV-1 particles from iMDDC to autologous CD4 T cells, and HIV-1 transcytosis through epithelial cells. Human urine partially disrupted both CCR5- and CXCR4-tropic HIV-1 particles, moderately decreased the adsorption of HIV-1 on dendritic cells, and partially decreased the transfer of HIV-1 particles from dendritic cells to autologous T cells. These findings demonstrate partial inactivation of HIV infectivity and suggest that voiding urine after coitus could play a potential role in reducing the risk of HIV infection by both mechanically flushing out and neutralizing the infectivity of HIV-1 particles present in the genital tract.

Statistical power and estimation of incidence rate ratios obtained from BED incidence testing for evaluating HIV interventions among young people.

BACKGROUND: The objectives of this study were to determine the capacity of BED incidence testing to a) estimate the effect of a HIV prevention intervention and b) provide adequate statistical power, when used among young people from sub-Saharan African settings with high HIV incidence rates. METHODS: Firstly, after having elaborated plausible scenarios based on empirical data and the characteristics of the BED HIV-1 Capture EIA (BED) assay, we conducted statistical calculations to determine the BED theoretical power and HIV incidence rate ratio (IRR) associated with an intervention when using BED incidence testing. Secondly, we simulated a cross-sectional study conducted in a population among whom an HIV intervention was rolled out. Simulated data were analyzed using a log-linear Poisson model to recalculate the IRR and its confidence interval, and estimate the BED practical power. Calculations were conducted with and without corrections for misclassifications. RESULTS: Calculations showed that BED incidence testing can yield a BED theoretical power of 75% or more of the power that can be obtained in a classical cohort study conducted over a duration equal to the BED window period. Statistical analyses using simulated populations showed that the effect of a prevention intervention can be estimated with precision using classical statistical analysis of BED incidence testing data, even with an imprecise knowledge of the characteristics of the BED assay. The BED practical power was lower but of the same magnitude as the BED theoretical power. CONCLUSIONS: BED incidence testing can be applied to reasonably small samples to achieve good statistical power when used among young people to estimate IRR.

High-risk human papillomavirus is associated with HIV acquisition among South African female sex workers.

BACKGROUND: Mounting evidence suggests an association between human papillomavirus (HPV) and HIV acquisition. This study aimed to explore this association among South African female sex workers (FSWs). METHODS: We used data from 88 HIV-negative FSWs who participated in a vaginal gel (COL-1492) trial. Cervicovaginal rinse samples, obtained before HIV-seroconversion, were genotyped into high-risk (HR-) and low-risk (LR-) HPV. HIV-adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) were estimated using Cox survival analysis. RESULTS: HR- and LR-HPV prevalences were 70.5% (95% CI:60.5-79.2) and 60.2% (95% CI:49.9-70.0), respectively. Twenty-five women HIV seroconverted. Controlling for background characteristics and other sexually transmitted infections, HIV aHR increased by a factor of 1.7 (95% CI:1.01-2.7, P(linear trend) = 0.045) for an increase of one unit of the number of HR-HPV genotypes. CONCLUSIONS: HIV seroconversion among FSWs is associated with genital HR-HPV infection. Further investigation is warranted, including testing the possible protective effect of available HPV vaccines on HIV acquisition.

Association of recent HIV infection and in-utero HIV-1 transmission.

OBJECTIVE: We previously developed a multiassay algorithm (MAA) to identify recent HIV infection that includes the BED-capture enzyme immunoassay, an avidity assay based on the Genetic Systems HIV-1/HIV-2 + O enzyme immunoassay, CD4 cell count, and HIV viral load. We used this MAA to evaluate the association between recent maternal HIV infection and in-utero transmission of HIV. METHODS: Plasma samples were collected at delivery from 2561 HIV-infected women in the postexposure prophylaxis of infants-Malawi trial. The MAA described above was used to identify women with recent HIV infection. Logistic regression models assessed association between recent HIV infection and in-utero HIV transmission (defined as a positive infant HIV DNA test at birth). RESULTS: Seventy-three women were identified as recently infected using the MAA. Those women were younger and had lower parity than women who were identified as not recently infected using the MAA (P < 0.0001 for age and parity). The frequency of in-utero HIV transmission was 17.8% among women identified as recently infected, compared with 6.7% among women identified as not recently infected (13/73 vs. 166/2488, P = 0.001). In a multivariate model, three factors were independently associated with in-utero HIV transmission: recent infection [adjusted odds ratio (AOR): 2.49, 95% confidence interval (CI): 1.30-4.78, P = 0.006], log(10) HIV viral load at delivery (AOR: 2.01, 95% CI: 1.60-2.51, P < 0.0001), and younger age (per 10 year increase, AOR: 0.66, 95% CI: 0.43-0.93, P = 0.02). CONCLUSION: Results obtained using a MAA suggest that recent maternal HIV acquisition is strongly associated with in-utero HIV transmission, independent of HIV viral load at delivery.

Association of low-risk human papillomavirus infection with male circumcision in young men: results from a longitudinal study conducted in Orange Farm (South Africa).

BACKGROUND: Low-Risk Human Papillomavirus (LR-HPV) genotypes 6 and 11 cause genital warts. This study investigated the association of LR-HPV infection with male circumcision (MC). METHODS: We used data from the South African MC trial conducted among young men. Urethral swabs, collected among intervention (circumcised) and control (uncircumcised) groups, were analyzed using HPV linear array. Adjusted LR-HPV prevalence rate ratio (aPPR) and Poisson mean ratio (aPMR) of number of LR-HPV genotypes were estimated using log-Poisson regression, controlling for background characteristics, sexual behaviour, and HIV and HSV-2 statuses. RESULTS: Compared to controls, LR-HPV prevalence and mean number of genotypes were significantly lower among the intervention group ((8.5% versus 15.8%; aPRR: 0.54, P < .001) and (0.33 versus 0.18; aPMR: 0.54, P < .001), resp.). Mean number of LR-HPV genotypes increased with number of lifetime sexual partners and decreased with education level and consistent condom use. CONCLUSIONS: This study shows a reduction in LR-HPV infection among circumcised men.

The effect of heterogeneity on HIV prevention trials.

BACKGROUND: Randomized controlled trials (RCTs) for the prevention of HIV heterosexual acquisition are usually conducted among adult African populations with high heterogeneity in individual risk of infection. PURPOSE: The objectives were to (a) review how this heterogeneity has been considered when designing and interpreting such RCTs, (b) evaluate its effect on the findings and the statistical power of these trials, and (c) assess the potential advantages of using the crossover design with single failure-time endpoint. METHODS: Individual-level HIV prevention RCTs conducted in Africa and published in the period 1998-2008 were reviewed. Using Monte Carlo simulations and statistical calculations, we assessed the effect of heterogeneity on the findings and the statistical power of HIV prevention RCTs. RESULTS: All reviewed RCTs used the parallel design. The heterogeneity in individual risk of infection within study sites was not used for stratification nor generally considered in the design and interpretation of RCTs. Simulations showed that in the context of high HIV incidence, high heterogeneity can lead to a substantial underestimation of the impact of an intervention and reduced statistical power. Calculations demonstrated that the crossover design allowed for similar or better estimation and statistical power. The crossover design has the ethical advantage of sharing the potential benefits and risks of the intervention between participants. LIMITATIONS: Only trials with two treatment arms and two follow-up periods were modeled. The baseline risk of infection of each participant was assumed to be constant over time and HIV status was assessed at the end of each follow-up period. CONCLUSIONS: The heterogeneity in individual risk of HIV infection is an underestimated problem which should be taken into account when designing and interpreting RCTs that test prevention methods of HIV heterosexual acquisition in adult African populations with high HIV incidence. When the effects of tested interventions are rapidly reversible, the use of the crossover design should be considered.

Exposé of misleading claims that male circumcision will increase HIV infections in Africa.

Despite over two decades of extensive research showing that male circumcision protects against heterosexual acquisition of HIV in men, and that includes findings from large randomized controlled trials leading to acceptance by the WHO/UNAIDS and the Cochrane Committee, opponents of circumcision continue to generate specious arguments to the contrary. In a recent issue of the Journal of Public Health in Africa, Van Howe and Storms claim that male circumcision will increase HIV infections in Africa. Here we review the statements they use in support of their thesis and show that there is no scientific basis to such an assertion. We also evaluate the statistics used and show that when these data are properly analyzed the results lead to a contrary conclusion affirming the major role of male circumcision in protecting against HIV infection in Africa. Researchers, policy makers and the wider community should rely on balanced scholarship when assessing scientific evidence. We trust that our assessment may help refute the claims by Van Howe and Storms, and provide reassurance on the importance of circumcision for HIV prevention.

Expose of Fallacious Claims that Male Circumcision will Increase HIV Infections in Africa

Despite over two decades of extensive research showing that male circumcision protects against heterosexual acquisition of HIV in men; and that includes findings from large randomized controlled trials leading to acceptance by the WHO/UNAIDS and the Cochrane Committee; opponents of circumcision continue to generate specious arguments to the contrary. In a recent issue of the Journal of Public Health in Africa; Van Howe and Storms claim that male circumcision will increase HIV infections in Africa. Here we review the statements they use in support of their thesis and show that there is no scientific basis to such an assertion. We also evaluate the statistics used and show that when these data are properly analyzed the results lead to a contrary conclusion affirming the major role of male circumcision in protecting against HIV infection in Africa. Researchers; policy makers and the wider community should rely on balanced scholarship when assessing scientific evidence. We trust that our assessment may help refute the claims by Van Howe and Storms; and provide reassurance on the importance of circumcision for HIV prevention

Prevalence, characteristics, and outcomes of patients presenting with cardiogenic unilateral pulmonary edema.

BACKGROUND: Cardiogenic unilateral pulmonary edema (UPE) is a rare entity, frequently leading to initial misdiagnosis. We sought to assess the prevalence of UPE and to determine its impact on prognosis compared with bilateral pulmonary edema. METHODS AND RESULTS: We studied the characteristics and outcomes of patients admitted to our institution for cardiogenic pulmonary edema during an 8-year period. The study population included 869 consecutive patients. The prevalence of UPE was 2.1%: 16 right-sided UPE (89%) and 2 left-sided UPE (11%). In patients with UPE, blood pressure was significantly lower (P≤0.01), whereas noninvasive or invasive ventilation and catecholamines were used more frequently (P=0.0004 and P<0.0001, respectively). The prevalence of severe mitral regurgitation in patients with bilateral pulmonary edema and UPE was 6% and 100%, respectively (P<0.0001). In patients with UPE, use of antibiotic therapy and delay in treatment were significantly higher (P<0.0001 and P=0.003, respectively). In-hospital mortality was 9%: 39% for UPE versus 8% for bilateral pulmonary edema (odds ratio, 6.9; 95% confidence interval, 2.6 to 18; P<0.001). In multivariate analysis, unilateral location of pulmonary edema was independently related to death whatever the model used (adjusted odds ratio, 6.5; 95% confidence interval, 1.3 to 32; P=0.021 for model A; and adjusted odds ratio, 6.8; 95% confidence interval, 1.1 to 41; P=0.037 for model B). CONCLUSIONS: Unilateral pulmonary edema represented 2.1% of cardiogenic pulmonary edema in our study, usually appeared as an opacity involving the right lung, and was always associated with severe mitral regurgitation. Unilateral pulmonary edema is related to an independent increased risk of mortality and should be promptly recognized to avoid delays in treatment.