Articles tagged as "Biomedical interventions and prevention tools"

August
2
2010

Microbicides

Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women

Abdool Karim Q, Abdool Karim S, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany ABM, Sibeko S, Mlisana KP,Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L,Taylor D, on behalf of the CAPRISA 004 Trial Group. Science. 2010; July [Epub ahead of print]

The CAPRISA 004 trial assessed 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) with placebo gel (n = 444) in sexually active, HIV uninfected 18 to 40 year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behaviour 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, i.e. person time of study observation, (38/680.6 women-years) compared to 9.1 per 100 women-years (60/660.7 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 seroconvertors. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.

For full text access click here:

Editors’ note: Following 20 years of research, including 11 effectiveness trials of 6 microbicide candidates that did not protect women from HIV, this groundbreaking study has responded to Zena Stein’s 1990 call for a women-controlled method for HIV prevention (Am J Pub Health 80, 460-462). The vaginal gel was inserted anytime in the 12 hours before anticipated sex and once in the 12 hours after sex. This dosing strategy was inspired by the effectiveness of antiretroviral prophylaxis at the time of exposure for preventing mother-to-child transmission. Whatever way the data are analysed, the results show effectiveness. Women who used the gel more consistently had more protection. WHO and UNAIDS are convening a meeting at the end of August 2010 at the invitation of the South African government to consider what further research is needed, what would be the regulatory pathway for tenofovir gel, and what programmatic issues would need to be addressed. An example of the latter would be the optimal frequency of HIV testing - having a test every month, as was done in the trial, would not be practical. When the results were presented in Vienna at IAS 2010 there was a standing ovation – an extremely rare event in science. You can download the slides and watch the presentation at: http://globalhealth.kff.org/AIDS2010/July-20/Safety-and-Effectiveness.aspx

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August
2
2010

Male circumcision

Male circumcision for HIV prevention - a cross-sectional study on awareness among young people and adults in rural Uganda.

Wilcken A, Miiro-Nakayima F, Hizaamu RN, Keil T, Balaba-Byansi D. BMC Public Health. 2010;10:209.

Medical male circumcision is now part of a comprehensive approach to HIV prevention. It has been shown that awareness of the protective effect of male circumcision leads to high acceptability towards the introduction of medical male circumcision services within countries. The objective of this survey was to identify factors determining awareness of male circumcision for HIV prevention. The authors interviewed 452 participants (267 adults >24 years of age; 185 youths 14-24 years) living in three rural Ugandan districts in 2008. Using a standardized questionnaire, they assessed socio-demographic parameters, awareness of male circumcision for HIV prevention, general beliefs/attitudes regarding male circumcision and male circumcision status. Determinants for awareness of male circumcision for HIV prevention were examined with multiple logistic regression models. Out of all adults, 52.1% were male  (mean+/-SD age 39.8+/-11 years), of whom 39.1% reported to be circumcised. Out of all youths, 58.4% were male (18.4+/-2.5), 35.0% circumcised. Adults were more aware of male circumcision for HIV prevention than youths (87.1% vs. 76.5%; p=0.004). In adults, awareness was increased with higher educational level compared to no school: primary school (adjusted OR 9.32; 95%CI 1.80-48.11), secondary (5.04; 1.01-25.25), tertiary (9.91; 0.76-129.18), university education (8.03; 0.59-109.95). Younger age and male sex were further significant determinants of increased awareness, but not marital status, religion, district, ethnicity, employment status, and circumcision status. In youths, they found a borderline statistically significant decrease of awareness of male circumcision for HIV prevention with higher educational level, but not with any other socio-demographic factors. Particularly Ugandans with low education, youths, and women, playing an important role in decision-making of male circumcision for their partners and sons, should be increasingly targeted by information campaigns about positive health effects of male circumcision.

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Editors’ note: While Ugandans wait for a clear endorsement by the government and community leaders of male circumcision for HIV prevention, information from the media and from nongovernmental and community-based organizations is increasing the understanding of those who will make the decisions at family level about male circumcision. Women are involved as mothers and sexual partners in such decisions, fathers can discuss male circumcision with their sons, and community advocates can raise the call for safe male circumcision services. As this study demonstrates, there is already a high level of awareness in rural Uganda. In such situations, the risk often increases that unsafe circumcision by untrained, poorly equipped operators working in unsanitary conditions will result in avoidable morbidity, mutilations, and mortality.

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June
21
2010

Vaccines

Neutralization of genetically diverse HIV-1 strains by IgA antibodies to the gp120-CD4-binding site from long-term survivors of HIV infection.

Planque S, Salas M, Mitsuda Y, Sienczyk M, Escobar MA, Mooney JP, Morris MK, Nishiyama Y, Ghosh D, Kumar A, Gao F, Hanson CV, Paul S. AIDS. 2010;24:875-84

The aim of the study was to identify an HIV epitope suitable for vaccine development.  Diverse HIV-1 strains express few structurally constant regions on their surface   vulnerable to neutralizing antibodies. The mostly conserved CD4-binding site of gp120 is essential for host cell binding and infection by the virus.  Antibodies that recognize the CD4-binding site are rare, and one component of the CD4-binding site, the 421-433 peptide region, expresses B-cell superantigenic character, a property predicted to impair the anti-CD4-binding site adaptive immune response. IgA samples purified from the plasma of patients with HIV infection were analyzed for the ability to bind synthetic mimetics containing the 416-433 gp120 region and full-length gp120. Infection of peripheral blood mononuclear cells by clinical HIV isolates was measured by p24 ELISA. IgA preparations from three patients with subtype B infection for 19-21 years neutralized heterologous, coreceptor CCR5-dependent subtype A, B, C, D, and AE strains with exceptional potency. The IgAs displayed specific binding of a synthetic 416-433 peptide mimetic dependent on recognition of the CD4-binding residues located in this region. Immunoadsorption, affinity chromatography, and mutation procedures indicated that HIV neutralization occurred by IgA recognition of the CD4-binding site.  These observations identify the 421-433 peptide region as a vulnerable HIV site to which survivors of infection can produce powerful neutralizing antibodies. This indicates that the human immune system can bypass restrictions on the adaptive B cell response to the CD4-binding site, opening the route to targeting the 421-433 region for attaining control of HIV infection. 

For abstract access click here:

Editors’ note: Studying the immune response of 3 long-term survivors, who had contracted HIV as children from contaminated blood products 19-21 years previously, revealed a region of HIV that is structurally conserved in genetically diverse HIV strains around the world and is immunogenic, meaning that it stimulates a robust immune response. Purified plasma IgA preparations from each of these 3 patients who were infected with sub-type B neutralized 18 genetically diverse clinical isolates from subtypes A, B, C, D, and AE. This is exciting news because the search for such a conserved epitope, i.e. the part of the virus that is recognized by the immune system and to which an antibody binds, is a holy grail. The site is the 421-433 region of the CD4 binding site of the virus. Interestingly, the autoimmune disease systemic lupus erythematosus produces antibodies to this epitope - and HIV and lupus rarely co-exist.

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June
21
2010

Vaccines

Mosaic vaccines elicit CD8(+) T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys.

Santra S, Liao HX, Zhang R, Muldoon M, Watson S, Fischer W, Theiler J, Szinger J, Balachandran H, Buzby A, Quinn D, Parks RJ, Tsao CY, Carville A, Mansfield KG,Pavlakis GN, Felber BK, Haynes BF, Korber BT, Letvin NL. Nat Med. 2010;16:324-8

An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses. It must generate CD8(+) T lymphocytes that control HIV replication and CD4(+) T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents a key challenge for creating an HIV vaccine. Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates. Here Santra and colleagues immunized rhesus monkeys by plasmid DNA prime and recombinant vaccinia virus boost with vaccine constructs expressing either consensus or polyvalent mosaic proteins. As compared to consensus immunogens, the mosaic immunogens elicited CD8(+) T lymphocyte responses to more epitopes of each viral protein than did the consensus immunogens and to more variant sequences of CD8(+) T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.

For abstract access click here: 

Editor’s note: In this macaque study, a mosaic immunogen was created by combining the gag and nef genes from geographically and sub-type diverse natural strains of HIV. A much broader immune response was elicited in macaques with this recombinant mix than with a consensus protein. Cellular immune responses to mosaic immunogens recognized a greater diversity of viral epitope variants, with CD+8 T lymphocytes showing significantly greater cross-reactivity, not only to more epitopes but also to more variant sequences of specific epitopes. Keeping up with viral evolution means expanding the breadth and depth of our CD8+ cytotoxic T lymphocyte responses – it looks like mosaic vaccines may be able to give us the leg up that we will need.

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May
13
2010

Post-exposure prophylaxis

Nonoccupational HIV post-exposure prophylaxis: a 10-year retrospective analysis.

Tissot F, Erard V, Dang T, Cavassini M. HIV Med. 2010 Mar. [Epub ahead of print]

The authors conducted a retrospective analysis of administration of non-occupational HIV post-exposure prophylaxis in a single centre where tracing and testing of the source of exposure were carried out systematically over a 10-year period. Files of all non-occupational HIV post-exposure prophylaxis requests between 1998 and 2007 were reviewed. Characteristics of the exposed and source patients, the type of exposure, and clinical and serological outcomes were analysed. Request for non-occupational HIV post-exposure prophylaxis increased by 850% over 10 years. Among 910 events, 58% were heterosexual exposures, 15% homosexual exposures, 6% sexual assaults and 20% nonsexual exposures. In 208 events (23%), the source was reported to be HIV positive. In the remaining cases, active source tracing enabled 298 HIV tests to be performed (42%) and identified 11 HIV infections (3.7%). Non-occupational HIV post-exposure prophylaxis was able to be avoided or interrupted in 31% of 910 events when the source tested negative. Of 710 patients who started non-occupational HIV post-exposure prophylaxis, 396 (56%) reported side effects, among whom 39 (5%) had to interrupt treatment. There were two HIV seroconversions, and neither was attributed to non-occupational HIV post-exposure prophylaxis failure. Non-occupational HIV post-exposure prophylaxis requests increased over time. HIV testing of the source person avoided non-occupational HIV post-exposure prophylaxis in 31% of events and was therefore paramount in the management of potential HIV exposures. Furthermore, it allowed active screening of populations potentially at risk for undiagnosed HIV infection, as shown by the increased HIV prevalence in these groups (3.7%) compared with a prevalence of 0.3% in Switzerland as a whole.

For abstract access click here:
http://www.ncbi.nlm.nih.gov/pubmed/20345883
Editors’ note: Conducting a randomised controlled trial to determine the efficacy of n-PEP (nonoccupational post-exposure prophylaxis) is not possible for ethical reasons but animal studies, prevention of mother-to-child transmission, and case-control studies after needle stick injuries support a protective effect. This large study conducted in Lausanne, Switzerland over 10 years found that the best way to prevent unnecessary exposure to antiretroviral drugs for 28 days (64% of people reported side effects, treatment costs are charged directly to the patient who gets partially reimbursed through insurance) was to contact the source and encourage them to learn their HIV status. Interestingly, police officers were significantly more likely to be able do this than people who were not police officers (57 vs. 32%; p<0.001). If the source was negative, then n-PEP was stopped. If the source was HIV-positive (23%), then the n-PEP drug regimen was adapted to the treatment history and available drug resistance profile. After 2006, if the source person had a viral load below 50 copies/mL while taking antiretroviral therapy for more than 6 months, n-PEP was not prescribed. One advantage of this programme was that it identified 11 source people who had no idea that they were HIV-positive – a prevalence 10 times that of the general Swiss population. What was the cost? There are likely enough data here for a cost-effectiveness analysis.
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April
11
2010

Condoms

Does it fit okay? Problems with condom use as a function of self-reported poor fit.

Crosby RA, Yarber WL, Graham CA, Sanders SA. Sex Transm Infect. 2010;86:36-8.

The study was set up to identify associations between men's self-reports of ill-fitting condoms and selected condom use problems, using an event-specific analysis. A convenience sample of men was recruited via advertisements in newspapers (two urban and one small town) and a blog on the website of a condom sales company. Men completed a questionnaire posted on the website of The Kinsey Institute for Research in Sex, Gender, and Reproduction. Inclusion criteria were: at least 18 years old, used condoms for penile-vaginal intercourse in the past 3 months and the ability to read English. In controlled, event-specific, analyses of 436 men, those reporting ill-fitting condoms (44.7%) were significantly more likely to report breakage (adjusted odds ratio (AOR 2.6), slippage (AOR 2.7), difficulty reaching orgasm, both for their female partners (AOR 1.9) and for themselves (AOR 2.3). In addition, they were more likely to report irritation of the penis (AOR 5.0) and reduced sexual pleasure, both for their female partner (AOR 1.6) and for themselves (AOR 2.4). Furthermore, they were more likely to report that condoms interfered with erection (AOR 2.0), caused erection loss (AOR 2.3), or became dry during sex (AOR 1.9). Finally, they were more likely to report removing condoms before penile-vaginal sex ended (AOR 2.0). Men and their female sex partners may benefit from public health efforts designed to promote the improved fit of condoms.

For abstract access click here: http://www.ncbi.nlm.nih.gov/pubmed/20157178
Editors’ note: Given that condoms are widely used to prevent pregnancy and that correct and consistent condom use is the cornerstone of HIV prevention for sexually active people, it is amazing that more research on the effects of ill-fitting condoms on penile erection, sexual pleasure, and discontinuation before the end of the sex act has not been done. This convenience sample of men from 28 countries (74% living in the US) defined ‘ill-fitting’ as ‘too long or too short’ and/or too narrow or too wide’. Almost 45% of men reporting ill-fitting condom use at the last sex act. It is not clear whether the problem is with the product itself or how it is applied. No wonder condoms get bad press! Much more work is needed to find out how this problem can be rectified – too many lives depend upon correct and consistent condom use.
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April
11
2010

Condoms

Low-Level CD4(+) T Cell Activation in HIV-Exposed Seronegative Subjects: Influence of Gender and Condom Use.

Camara M, Dieye TN, Seydi M, Diallo AA, Fall M, Diaw PA, Sow PS, Mboup S, Kestens. J Infect Dis. 2010;201:835-42

Immune activation has been suggested to increase susceptibility to human immunodeficiency virus type 1 (HIV-1) transmission, while at the same time it could be deemed essential for mounting an effective antiviral immune response. In this study, Camara and colleagues compared levels of T cell activation between exposed seronegative partners in HIV-1 discordant couples and HIV-unexposed control subjects in Dakar, Senegal. Exposed seronegative subjects showed lower levels of CD38 expression on CD4(+) T cells than did control subjects. However, this was found to be associated with concurrent differences in the use of condoms: exposed seronegative subjects reported a higher degree of condom use than did control subjects, which correlated inversely with CD38 expression. In addition, they observed markedly higher levels of T cell activation in women compared with men, irrespective of sexual behaviour. These findings question the relevance of low-level CD4(+) T cell activation in resistance to HIV-1 infection and underscore the need to take gender and sexual behaviour characteristics of high-risk populations into account when analyzing correlates of protective immunity

For abstract access click here: http://www.ncbi.nlm.nih.gov/pubmed/20136413
Editors’ note: Basic scientists have found that host factors such as genetic predisposition (e.g. CCR5-delta 32 mutation), intrinsic cellular defences (e.g. β-chemokines), and innate or adaptive immune responses (e.g. natural killer cell activity) may help explain why HIV-seronegative people resist HIV infection when they are exposed sexually multiple times. It is true that viral load in the partner is important, as are the characteristics of the infecting virus, however the low levels of immune activation found in a number of studies of exposed, seronegative people have been intriguing. It may mean fewer activated T cells are around for HIV to invade. However, this study suggests that basic scientists should be paying more attention to human behaviour and to sex. HIV-negative partners in Senegalese serodiscordant couples that always used condoms had decreased CD4+ T- cell activation compared to HIV-negative low risk controls. This was likely due to less exposure to genital secretions that can cause immune activation. This finding was independent of infection with herpes simplex virus-2 and was more marked in men (85% of male versus 46% of female seronegative partners reported always using condoms). More than condom use may be playing a role too since women generally seem to have higher T-cell activation. In studies of seronegative exposed individuals aimed at finding promising avenues for therapeutics and vaccine development, it is important to know about the people behind the samples: their sex and their condom use practices.
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April
11
2010

Vaccines

Immunology and the elusive AIDS vaccine.

Virgin HW, Walker BD. Nature. 2010;464:224-31.

Developing a human immunodeficiency virus (HIV) vaccine is critical to end the global acquired immunodeficiency syndrome (AIDS) epidemic, but many question whether this goal is achievable. Natural immunity is not protective, and despite immunogenicity of HIV vaccine candidates, human trials have exclusively yielded disappointing results. Nevertheless, there is an indication that success may be possible, but this will be dependent on understanding the antiviral immune response in unprecedented depth to identify and engineer the types of immunity required. Here the authors outline fundamental immunological questions that need to be answered to develop a protective HIV vaccine, and the immediate need to harness a much broader scientific community to achieve this goal.

For abstract access click here: http://www.ncbi.nlm.nih.gov/pubmed/20220841
Editors’ note: This thorough review of the state of our knowledge of HIV-related immunology points out that an effective HIV vaccine is an achievable goal but that there are ‘knowable unknowns’ that must be explored to gain the knowledge that is essential for translation into vaccine-induced protection. There are signals that vaccination may work from the Thai RV144 trial and from monkey studies but huge gaps in our knowledge remain, starting with the means by which the vast majority of HIV exposures do not result in infection. Making the case for ‘re-embracing CD4 T cells’ because basic rules of immunology indicate that it will be impossible to generate long-lived, stable, high-level vaccine-induced immunity without them, the authors also bring B cells and antibody back into focus. They argue that unexplored interactions between B cells, antibody responses, and T cells are ‘knowable unknowns’ critical to HIV vaccine strategies. The possibility of creating an evolutionary trap by driving HIV into a fitness dead-end, targeting epitopes in fitness-critical regions of viral proteins, is appealing, but the overarching call for attracting experts from other fields to tap into the wealth of current knowledge on HIV pathogenesis is perhaps the most compelling argument. Their insights could enhance our understanding of HIV immunology and that would have spin-offs beyond HIV for hepatitis B, hepatitis C, malaria, cancer, and tuberculosis, all of which face similar immunological issues.
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April
11
2010

Male circumcision

Complications of circumcision in male neonates, infants and children: a systematic review.

Weiss HA, Larke N, Halperin D, Schenker I. BMC Urol. 2010;10(1):2.

Approximately one in three men are circumcised globally, but there are relatively few data on the safety of the procedure. The aim of this paper is to summarize the literature on frequency of adverse events following paediatric circumcision, with a focus on developing countries. PubMed and other databases were searched with keywords and MeSH terms including infant/newborn/paediatric/child, circumcision, complications, and adverse events. Searches included all available years and were conducted on November 6th 2007 and updated on February 14th 2009. Additional searches of the Arabic literature included searches of relevant databases and University libraries for research theses on male circumcision. Studies were included if they contained data to estimate frequency of adverse events following neonatal, infant and child circumcision. There was no language restriction. A total of 1349 published papers were identified, of which 52 studies from 21 countries met the inclusion criteria. The Arabic literature searches identified 46 potentially relevant papers, of which six were included. Sixteen prospective studies evaluated complications following neonatal and infant circumcision. Most studies reported no severe adverse events (SAE), but two studies reported severe adverse event frequency of 2%. The median frequency of any complication was 1.5% (range 0-16%). Child circumcision by medical providers tended to be associated with more complications (median frequency 6%; range 2-14%) than for neonates and infants. Traditional circumcision as a rite of passage is associated with substantially greater risks, more severe complications than medical circumcision or traditional circumcision among neonates. Studies report few severe complications following circumcision. However, mild or moderate complications are seen, especially when circumcision was undertaken at older ages, by inexperienced providers or in non-sterile conditions. Paediatric circumcision will continue to be practiced for cultural, medical and as a long-term HIV/sexually transmitted infection prevention strategy. Risk-reduction strategies including improved training of providers, and provision of appropriate sterile equipment, are urgently needed.

For full text access click here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835667/?tool=pubmed
Editors’ note: Circumcision of neonates and infant boys is cheaper than adult male circumcision, does not generally require suturing, and healing occurs much faster than in older boys, adolescents, and men. As this review of 16 prospective studies reveals, complication rates are low with bleeding and infection being the most common adverse events for methods using the Plastibell, Gomco clamp, freehand circumcision, or a combination of methods. Freehand circumcision had the highest complication rate (27%) and midwives (19%) had higher rates than doctors (7%). But different levels of training and supervision among doctors resulted in complication rates of 1.6% in a public teaching hospital versus 20% at private hospitals. WHO and UNAIDS recommend that high HIV prevalence countries consider neonatal circumcision in addition to adult male circumcision as a longer-term HIV prevention strategy and several African countries are planning to implement pilot projects for neonatal and infant circumcision, having assessed acceptability. Modelling shows that the effects of introducing neonatal circumcision now will take up to 20 years to show epidemic impact but in the grand scheme of things this investment could pay off over the short to medium term in improved hygiene and reduced urinary tract infections in infant boys and reduced HIV infections and genital ulcer diseases in young men down the line.
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February
15
2010

Male circumcision

Male circumcision and risk of male-to-female HIV-1 transmission: a multinational prospective study in African HIV-1-serodiscordant couples.

Baeten JM, Donnell D, Kapiga SH, Ronald A, John-Stewart G, Inambao M, Manongi R, Vwalika B, Celum C; for the Partners in Prevention HSV/HIV Transmission Study Team. AIDS. 2009. Dec [Epub ahead of print].

Male circumcision reduces female-to-male HIV-1 transmission risk by approximately 60%. Data assessing the effect of circumcision on male-to-female HIV-1 transmission are conflicting, with one observational study among HIV-1-serodiscordant couples showing reduced transmission but a randomized trial suggesting no short-term benefit of circumcision. Data were collected as part of a prospective study among African HIV-1-serodiscordant couples were analyzed for the relationship between circumcision status of HIV-1-seropositive men and risk of HIV-1 acquisition among their female partners. Circumcision status was determined by physical examination. Cox proportional hazards analysis was used. A total of 1096 HIV-1-serodiscordant couples in which the male partner was HIV-1-infected were followed for a median of 18 months; 374 (34%) male partners were circumcised. Sixty-four female partners seroconverted to HIV-1 (incidence 3.8 per 100 person-years). Circumcision of the male partner was associated with a nonstatistically significant approximately 40% lower risk of HIV-1 acquisition by the female partner (hazard ratio 0.62, 95% confidence interval 0.35-1.10, P = 0.10). The magnitude of this effect was similar when restricted to the subset of HIV-1 transmission events confirmed by viral sequencing to have occurred within the partnership (n = 50, hazard ratio 0.57, P = 0.11), after adjustment for male partner plasma HIV-1 concentrations (hazard ratio 0.60, P = 0.13), and when excluding follow-up time for male partners who initiated antiretroviral therapy (hazard ratio 0.53, P = 0.07). Among HIV-1-serodiscordant couples in which the HIV-1-seropositive partner was male, the authors observed no increased risk and potentially decreased risk from circumcision on male-to-female transmission of HIV-1.

For access to abstract click here: 1 

Editors’ note: The trend seen here among 1096 couples toward a protective effect of male circumcision for HIV-negative women in discordant partnerships is intriguing. Sexual behaviours of couples with circumcised men were similar to those in which the man was not circumcised, only genetically-linked transmissions (i.e. transmissions within the couple) were considered (incidence 3.0 per 100 person years), and follow-up time after initiation of antiretroviral treatment (when viral loads presumably fell) was excluded. The result was a borderline statistically significant 47 per cent reduced risk of HIV-1 acquisition in women. Possible mechanisms that might explain lower risk for women are reduced risk of sexually transmitted infections in circumcised men or reduced likelihood of direct HIV transmission that would have otherwise occurred as a result of microtrauma or inflammation of the foreskin.

The effects of circumcision on the penis microbiome.

Price LB, Liu CM, Johnson KE, Aziz M, Lau MK, Bowers J, Ravel J, Keim PS, Serwadda D, Wawer MJ, Gray RH., PLoS One. 2010. 5:e8422.

Circumcision is associated with significant reductions in HIV, HSV-2, and HPV infections among men and significant reductions in bacterial vaginosis among their female partners. The authors assessed the penile (coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3-V4 hypervariable regions. Taxonomic classification was performed using the RDP Naïve Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significantdecrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families-Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)-were uniquely abundant before circumcision. Within these families they identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp. The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.

For full text access click here: 1

Editors’ note: Although molecular analyses have been used to characterise the microbiota or microbial community in the vagina, this is the first molecular assessment of the bacterial diversity found in the male genital mucosa. This pre-post circumcision study of 12 men shows that removing the foreskin removes the oxygen-poor environment of the mucosa under the foreskin that provides a warm, moist home for bacteria, many of which are anaerobic and are associated with bacterial vaginosis in women. This helps explain why the female partners of circumcised men have fewer sexually transmitted infections and less bacterial vaginosis. Getting rid of these bacteria through circumcision reduces mucosal inflammation and may provide part of the explanation for the reduced risk of HIV, herpes simplex-2, and human papilloma virus (HPV) infections in circumcised men.

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