Circumcision Status and Risk of HIV Acquisition during Heterosexual Intercourse for Both Males and Females: A Meta-Analysis

Lei, Jun; Liu, Liang Ren; Wang, Qiang; Yan, Shi bing; Yang, Lu; Song, Tu R.; Yuan, Hai Chao; Lv, Xiao; Han, Ping

doi:10.1371/journal.pone.0125436

Cited by 34 publications

(33 citation statements)

References 30 publications

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“…The protective effect of voluntary medical male circumcision (VMMC) against sexually transmitted diseases has been well-documented [10,11], and integration with existing HIV prevention strategies is expected to maximize benefits both for men and women [3, 12]. There is strong evidence from observational data and three randomized controlled trials that medically circumcising men lowers their risk of acquiring HIV through heterosexual intercourse by between 38% and 66% [13–15, 7, 8, 10]. In turn, as a result, VMMC also provides long-term indirect protection to women [3, 12].…”

Section: Introductionmentioning

confidence: 99%

The Cost of Voluntary Medical Male Circumcision in South Africa

Tchuenche

Palmer²,

Haté

et al. 2016

PLoS ONE

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Given compelling evidence associating voluntary medical male circumcision (VMMC) with men’s reduced HIV acquisition through heterosexual intercourse, South Africa in 2010 began scaling up VMMC. To project the resources needed to complete 4.3 million circumcisions between 2010 and 2016, we (1) estimated the unit cost to provide VMMC; (2) assessed cost drivers and cost variances across eight provinces and VMMC service delivery modes; and (3) evaluated the costs associated with mobilize and motivate men and boys to access VMMC services. Cost data were systematically collected and analyzed using a provider’s perspective from 33 Government and PEPFAR-supported (U.S. President's Emergency Plan for AIDS Relief) urban, rural, and peri-urban VMMC facilities. The cost per circumcision performed in 2014 was US$132 (R1,431): higher in public hospitals (US$158 [R1,710]) than in health centers and clinics (US$121 [R1,309]). There was no substantial difference between the cost at fixed circumcision sites and fixed sites that also offer outreach services. Direct labor costs could be reduced by 17% with task shifting from doctors to professional nurses; this could have saved as much as $15 million (R163.20 million) in 2015, when the goal was 1.6 million circumcisions. About $14.2 million (R154 million) was spent on medical male circumcision demand creation in South Africa in 2014—primarily on personnel, including community mobilizers (36%), and on small and mass media promotions (35%). Calculating the unit cost of VMMC demand creation was daunting, because data on the denominator (number of people reached with demand creation messages or number of people seeking VMMC as a result of demand creation) were not available. Because there are no “dose-response” data on demand creation ($X in demand creation will result in an additional Z% increase in VMMC clients), research is needed to determine the appropriate amount and allocation of demand creation resources.

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Section: Introductionmentioning

confidence: 99%

The Cost of Voluntary Medical Male Circumcision in South Africa

Tchuenche

Palmer²,

Haté

et al. 2016

PLoS ONE

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“…Male circumcision may reduce HIV-1 transmission by up to 70% [115–117], suggesting that intravesicular HIV-1 sequestration in foreskin epithelium in vivo may occur, and therefore removal of epithelium prevents the spread of sequestered virus.…”

Section: Discussionmentioning

confidence: 99%

Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction

et al. 2017

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Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual transmission of virus, respectively. To study the mechanisms of HIV-1 transmission through mucosal epithelium, we established polarized tonsil, cervical and foreskin epithelial cells. Analysis of HIV-1 transmission through epithelial cells showed that approximately 0.05% of initially inoculated virions transmigrated via epithelium. More than 90% of internalized virions were sequestered in the endosomes of epithelial cells, including multivesicular bodies (MVBs) and vacuoles. Intraepithelial HIV-1 remained infectious for 9 days without viral release. Release of sequestered intraepithelial HIV-1 was induced by the calcium ionophore ionomycin and by cytochalasin D, which increase intracellular calcium and disrupt the cortical actin of epithelial cells, respectively. Cocultivation of epithelial cells containing HIV-1 with activated peripheral blood mononuclear cells and CD4+ T lymphocytes led to the disruption of epithelial cortical actin and spread of virus from epithelial cells to lymphocytes. Treatment of epithelial cells with proinflammatory cytokines tumor necrosis factor-alpha and interferon gamma also induced reorganization of cortical actin and release of virus. Inhibition of MVB formation by small interfering RNA (siRNA)-mediated silencing of its critical protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) expression reduced viral sequestration in epithelial cells and its transmission from epithelial cells to lymphocytes by ~60–70%. Furthermore, inhibition of vacuole formation of epithelial cells by siRNA-inactivated rabankyrin-5 expression also significantly reduced HIV-1 sequestration in epithelial cells and spread of virus from epithelial cells to lymphocytes. Interaction of the intercellular adhesion molecule-1 of epithelial cells with the function-associated antigen-1 of lymphocytes was important for inducing the release of sequestered HIV-1 from epithelial cells and facilitating cell-to-cell spread of virus from epithelial cells to lymphocytes. This mechanism may serve as a pathway of HIV-1 mucosal transmission.

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“…He then attempts to adjust for suspected heterogeneity by fitting a meta-regression model that explains the heterogeneity in terms of study-level covariates. A positive finding would add to existing RCTs and statistical analyses that have consistently found MC lowers the risk HIV acquisition during heterosexual intercourse (Auvert et al, 2005;Bailey et al, 2007;Gray et al, 2007;Lei et al, 2015;Siegfried et al, 2009;Weiss et al, 2008). But the manner in which Van Howe performs his meta-regression is somewhat opaque, as we explained.…”

Section: Discussionmentioning

confidence: 83%

Circumcision is a primary preventive against HIV infection: Critique of a contrary meta-regression analysis by Van Howe

Morris

Barboza

Wamai

et al. 2016

Global Public Health

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A meta-analysis by Van Howe of 109 populations confirms the well-known association of male circumcision (MC) with reduced HIV prevalence. He then performed meta-regression adjusting for location, risk and MC prevalence. When one or two of these adjustments in combination were applied MC appeared protective, but when all three were introduced the association remained significant in high-risk populations, but not in general populations within Africa with a hypothetical MC prevalence of <25% or elsewhere with hypothetical MC prevalence of <75%. However, many MC prevalence values given differed from those reported in references cited (including all US studies). This and other problems invalidate his adjustments for MC prevalence, undermining most of his meta-regression results. Meta-regression is a highly sophisticated statistical tool and is prone to error if not applied correctly. The study contained a high risk of bias arising from confounding. We also question his use of crude, rather than adjusted, odds ratios and his inclusion of unpublished data, so precluding replication by others. Flawed statistics, opaque presentation of results and inclusion of previously repudiated arguments downplaying a role for MC in HIV prevention programmes should lead readers to be sceptical of the findings and conclusions of Van Howe's study.

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Circumcision Status and Risk of HIV Acquisition during Heterosexual Intercourse for Both Males and Females: A Meta-Analysis

Cited by 34 publications

References 30 publications

The Cost of Voluntary Medical Male Circumcision in South Africa

The Cost of Voluntary Medical Male Circumcision in South Africa

Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction

Circumcision is a primary preventive against HIV infection: Critique of a contrary meta-regression analysis by Van Howe

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