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Barriers to Male Circumcision HIV Prevention
 
 
  Male circumcision to cut HIV risk in the general population COMMENT
 
The Lancet Feb 24, 2007; 369:617-619
 
Marie-Louise Newell a b and Till Barnighausen a c
a. Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, KwaZulu-Natal 3935, South Africa
b. Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, UK
c. Department of Population and International Health, Harvard School of Public Health, Boston, Massachusetts, USA
 
".....whether and how the clinical evidence can be translated into routine practice....Will circumcision reduce condom use and increase risk taking? Although in the trials presented today there was no evidence of increased risky sexual behaviour associated with circumcision, such findings need cautious interpretation, because the declining incidence in the control group in Rakai-which, although not statistically significant, reduces the difference between the groups-possibly suggests an effect of counselling and education in this setting...... Acceptance of the clinical evidence that male circumcision is effective in preventing transmission of HIV does not automatically imply that governments and international organisations should strive to start circumcision programmes. Before male circumcision can become a health policy, countries need to develop capacity to educate and counsel people about the operation. The challenge will be to learn how to convey the public-health message that, although circumcision reduces the risk of HIV, it is nevertheless necessary to always use condoms because circumcised individuals can still become infected.... Also needed are studies to investigate whether male circumcision will be accepted, and whether traditional circumcision rites could be integrated into a general policy.... The ethics of mass circumcisions to reduce HIV transmission need to be addressed. Is it ethical to circumcise everybody even if many will not benefit from the intervention..."
 
In today's Lancet, results from two randomised trials show considerable benefit of male circumcision in reducing HIV incidence in men,1,2 confirming findings from an earlier trial in South Africa.3 The recent focus on antiretroviral treatment-although necessary and appropriate-has made primary prevention a secondary issue. Renewed interest in HIV prevention is welcome.
 
The South African trial was done in a periurban setting near Johannesburg,3 in 3274 men aged 18-24 years randomised to immediate (n=1617) or later (n=1657) circumcision. The trial was stopped after a planned interim analysis showed a significant 60% relative reduction in HIV risk associated with circumcision. The participants were from the general population and loss to follow-up was low, supporting the generalisability of the findings. However, concern was expressed about the randomisation procedures, the slight imbalance in baseline characteristics between groups, and potential selection bias. WHO and other UN agencies issued a supportive statement,4 but urged restraint while awaiting the results of two ongoing trials, presented today.
 
Robert Bailey and colleagues' trial1 in Kisumu, Kenya, was also done in men aged 18-24 years, randomly assigned to circumcision (n=1391) or delayed circumcision (n=1393).1 The trial was stopped after an unscheduled interim analysis in December, 2006, when evidence emerged of a significant benefit from circumcision. The HIV incidence rate was high, at 11 per 100 person-years in the circumcised men and 21 per 100 person-years in the control group (or 21% and 42%, respectively, over 2 years). There was an estimated 53% (unadjusted modified intention-to-treat analysis) to 60% (as-treated analysis) reduction in relative risk of HIV infection associated with male circumcision.
 
Ronald Gray and co-workers' study2 in Rakai, Uganda, included 4996 men aged 15-49 years; 2474 were randomised to immediate and 2522 to delayed circumcision. As with the trial in Kenya, this trial was stopped early after an interim analysis showed significant efficacy. HIV incidence was 066 per 100 person-years in the circumcision group and 133 per 100 person-years in the control group.2 The estimated reduction in the relative risk of infection with HIV was 51% (unadjusted modified intention-to-treat analysis) to 55% (as-treated analysis). Both trials were methodologically and analytically sound.
 
Thus three randomised trials now provide firm evidence that the risk of acquiring HIV is halved by male circumcision. Applying the circumcision efficacy2 to the age-specific HIV incidence rates from a large population-based longitudinal HIV survey5 in rural KwaZulu-Natal, South Africa, we find that circumcision would prevent an estimated 35 000 new HIV infections in 2007 alone in the 25 million mostly uncircumcised men in the province (figure 1).6
 
However, male circumcision does not provide 100% protection, and condoms remain an important part of HIV prevention. With the acknowledgment that consistent condom use is difficult and rare, the finding of considerable benefit of circumcision with inconsistent condom use is noteworthy.2 Will circumcision reduce condom use and increase risk taking? Although in the trials presented today there was no evidence of increased risky sexual behaviour associated with circumcision, such findings need cautious interpretation, because the declining incidence in the control group in Rakai-which, although not statistically significant, reduces the difference between the groups-possibly suggests an effect of counselling and education in this setting.2
 
Acceptance of the clinical evidence that male circumcision is effective in preventing transmission of HIV does not automatically imply that governments and international organisations should strive to start circumcision programmes. Before male circumcision can become a health policy, countries need to develop capacity to educate and counsel people about the operation. The challenge will be to learn how to convey the public-health message that, although circumcision reduces the risk of HIV, it is nevertheless necessary to always use condoms because circumcised individuals can still become infected. Also needed are studies to investigate whether male circumcision will be accepted, and whether traditional circumcision rites could be integrated into a general policy. Evidence seems to indicate that the acceptability of circumcision in Africa is high;7,8 80% of eligible control participants in the Ugandan trial had agreed to be circumcised by the time the study was closed.2 However, acceptability could vary greatly across African communities,7,8 and could be different in other populations with a high burden of HIV-eg, in southeast Asia. In South Africa, dozens of boys and young men are injured or die every year after traditional circumcisions.9 Can traditional practices be adapted to maintain their cultural meaning while ensuring the safety of the circumcised, or can clinical circumcision take on the cultural function (figure 2)?
 
Operational studies are needed to compare different technologies and health-systems approaches to scale up male circumcision and establish safety and cost-effectiveness. Although safe adult male circumcisions can be delivered in resource-poor settings, health workers that can do circumcision without much further training are likely to be scarce.10 Circumcisions should be done by individuals with primary-care surgical skills in facilities that can guarantee the sterility of the operation and appropriate wound dressing to ensure low rates of adverse events similar to those seen in the trials.1-3,10
 
The ethics of mass circumcisions to reduce HIV transmission need to be addressed. Is it ethical to circumcise everybody even if many will not benefit from the intervention-eg, people who do not engage in risky sexual behaviour or are HIV positive? Whether circumcised men who are infected with HIV are also less likely to transmit the infection to their uninfected partners is not known; a trial studying the male-to-female preventive effect of circumcision is in progress. Is it ethical to circumcise infants and young children who cannot consent to the procedure? A recent law in South Africa banning circumcision under the age of 16 years is an example of an effort to protect children from unsafe circumcision.11
 
We now have proof of a permanent intervention that can reduce the risk of HIV infection in men, which is positive news about prevention after past and current disappointments.12,13 The excitement that the results of these trials will surely generate should not cause us to forgo due diligence in investigating whether and how the clinical evidence can be translated into routine practice. Otherwise, a historic opportunity to save lives could be squandered.
 
Newer approaches to HIV prevention EDITORIAL
 
The Lancet Feb 24, 2007; 369:615
 
The publication of two randomised trials in today's Lancet signals a new era for HIV prevention. The studies, in Uganda and Kenya, show that male circumcision halves the risk of adult males contracting HIV through heterosexual intercourse.
 
This success is extremely welcome news. The results of these trials, along with the findings of a preliminary South African trial published in 2005, now provide a solid evidence-base to inform health policy. Large-scale implementation of male circumcision has the potential to substantially reduce HIV transmission, particularly in sub-Saharan Africa. But, as an accompanying Comment and Viewpoint highlight, this new intervention presents many opportunities but also raises many questions.
 
One such question is the effect of male circumcision on women. Initially, wide-scale implementation of male circumcision will lower HIV infection in men. But modelling studies suggest that over time women could benefit from an effect similar to the herd immunity seen with mass immunisation. Male circumcision might also directly protect against male-to-female transmission of HIV. A trial to test this hypothesis is under way in Uganda, with results expected in 2008.
 
In the meantime, new approaches for HIV prevention in women are urgently needed. According to UNAIDS, during the past 2 years, the number of women and girls infected with HIV has increased in every region of the world. Although condoms can provide a high level of protection (80-90%) against sexual transmission of HIV if used consistently and properly, many women are not in a position to persuade partners to use them. The development of new technologies that put HIV prevention in the hands of women is therefore crucial.
 
Microbicides-vaginally applied antimicrobial medications that can kill, block, or inactivate HIV-are one such intervention. According to a Review of microbicide drug candidates, published online by The Lancet on Feb 14, a large number of compounds-more than 60 at the start of 2006-are in the development pipeline. And, at the beginning of this year, five phase III trials testing different formulations were under way.
 
Sadly, however, the microbicide field was hit with bad news on Feb 1, when the International AIDS Society announced that two phase III trials of the candidate microbicide cellulose sulphate had been stopped because preliminary results suggested a potential increased risk for HIV in women who used the compound. At present, there is no explanation as to why cellulose sulphate was associated with a higher risk of HIV infection than placebo.
 
Although the halting of these trials is a disappointing setback for microbicide research, the investigators deserve praise for acting quickly as soon as an adverse effect became apparent. In the development of any new product, ruling out potential candidates is essential for progress. As for the remaining late-stage microbicide trials, if they prove successful, first-generation products could be available by 2009. If they fail, second-generation products could become available by 2012.
 
A much more distant hope for HIV prevention is the development of an effective vaccine that can offer long-term protection against the wide spectrum of HIV variants that exist. Despite the fact that there are now more than 30 vaccine candidates in clinical trials, and three of these are in advance stage testing (phase IIb and phase III), many obstacles still lie in the way of the development of a truly effective HIV preventive vaccine.
 
The genetic diversity of HIV presents an enormous challenge for researchers. And, because the virus has the ability to evade neutralising antibodies produced by natural immunity, the standard vaccine strategy of mimicking natural infection to induce antibodies has so far proved impossible. Strengthening cell-mediated immunity offers another possible route to success. About 90% of candidate HIV vaccines in development use this approach. These products will not prevent infection. But it is hoped that they will lower viral load and therefore progression to AIDS and secondary transmissions. Whether even this will be possible remains to be seen. Some observers believe that a vaccine to prevent HIV will never be achieved.
 
Ultimately, even if an HIV preventive vaccine or microbicide were to be developed, they are unlikely to be 100% effective. This prospect, together with the knowledge that male circumcision offers only partial protection against HIV infection, means that the future of HIV prevention will involve combining new methods with existing approaches, such as condom use. The emerging truth is that no single approach alone will be able to stem the spread of HIV.
 
 
 
 
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