Primary source: Proceedings of the National Academy of Sciences

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CAPE TOWN, South Africa, July 20 — From the female point of view, male circumcision is either no big deal or a positive improvement, Ugandan researchers said.

• Explain to interested patients that circumcision has been shown to reduce the risk of acquiring HIV for heterosexual men in Africa.
• Note that this study shows that an overwhelming majority of women think their own sexual satisfaction remains the same or even gets better after the procedure.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Among women whose partners took part in the landmark circumcision trial in Rakai, Uganda, only a handful reported that the procedure reduced their sexual satisfaction, according to Godfrey Kigozi, MD, of the Rakai Health Sciences Program.

The remaining 97% said their satisfaction was unchanged or improved, he said during a poster discussion session at the fifth International AIDS Society conference on pathogenesis, treatment, and prevention of HIV.

The Rakai circumcision trial is one of three studies that have shown that the procedure reduces the risk acquiring HIV for heterosexual men by more than 50%.

As a follow-up to the Rakai study, Dr. Kigozi and colleagues enrolled 455 women whose partners had the procedure during the trial and asked them to report their sexual satisfaction before and after.

Among the 2.9% who said their sexual satisfaction was reduced, the top two reasons — each reported by six of 13 participants — were lower levels of desire on both sides. (Participants could give multiple reasons, Dr. Kigozi said.)

Among the 39.8% who said things were better, the top reason — reported by 51 of 177 women — was better hygiene.

Interestingly, 45 of the 177 reported better sex because their partner took longer to achieve orgasm — the same reason two unhappy women gave for their dissatisfaction.

Among other reasons for better sex:

• 44 women said their partner wanted sex more often, a reason also given by one woman who was unhappy with her state of sexual satisfaction
• 26 said their partner had less or no difficulty maintaining an erection and 18 said he had less or no difficulty getting an erection in the first place
• 20 said they achieved orgasm more often

The findings are good news because they show that one possible barrier to the widespread use of circumcision to fight HIV — objections from women — doesn’t exist, according to Naomi Block, MD, of the CDC, who chaired a session at which the study was presented.

On the other hand, Dr. Block said, the result is not unexpected — more than a dozen earlier reports had said that women didn’t expect much to change after a partner’s circumcision.

“Women were very positive about it,” she said.

But those reports, she said, were based on interviews with women whose partners had not been circumcised, while the Rakai study involved women with experience both before and after the procedure.

Dr. Kigozi said the finding parallels earlier research on men’s opinions of sexual satisfaction after circumcision, with 97% saying it was either unchanged or better.

Primary source: IAS Conference on HIV Pathogenesis and Treatment

Source reference:
Kigozi G et al. “Sexual satisfaction of women partners of circumcised men in a randomized trial of male circumcision in Rakai, Uganda” IAS 2009; Abstract MOPDC104.

CAPE TOWN, South Africa, July 21 — In places like South Africa, starting anti-HIV treatment earlier than current WHO guidelines suggest for the developing world would save lives and reduce opportunistic infections, researchers said.

• Explain to interested patients that evidence is mounting that early treatment of HIV results in better clinical outcomes but that guidelines in Africa still suggest waiting until the disease is relatively advanced.
• Add that clinical trials aimed at seeing if earlier therapy would improve outcomes in sub-Saharan Africa are under way, but won’t report results for several years.
• Note that this study, using a mathematical model, suggests that in the meantime, clinicians should start treatment earlier.

Such a change in clinical practice would also be cost-effective, according to Rochelle Walensky, MD, of the Massachusetts General Hospital in Boston, and colleagues.

The conclusions are based on a mathematical model of the HIV epidemic in South Africa and are intended to guide clinical practice until several formal clinical trials studying the issue are complete, Dr. Walensky and colleagues reported in the Aug. 4 issue of the Annals of Internal Medicine.

The researchers also reached similar conclusions using data from Cote d’Ivoire and presented them in a poster here at the fifth International AIDS Society conference on pathogenesis, treatment, and prevention of HIV.

The current standard for starting HIV treatment in South Africa followed World Health Organization guidelines for the developing world — a patient is eligible for treatment when his or her CD4-positive T cell count falls below 200 per cubic millimeter of plasma or when there is an AIDS-defining illness.

But guidelines in the developed world now suggest starting at a higher level — 350 cells per cubic millimeter — and some recent studies have suggested that clinical outcomes would be even better if the threshold were set to 500 cells or more.

Clinical trials are under way in Africa to settle the issue, but they won’t report for another five years. In the meantime, Dr. Walensky and colleagues said, their model may provide guidance to clinicians.

The bottom line, they said, is that in all cases, starting therapy at the 350-cell threshold saved more lives, prevented more disease, and cost more, compared with a threshold of 250 cells.

The researchers estimated that such a threshold would mean 4.7 million people would be eligible for therapy in South Africa over the next five years.

Under the assumption that 10% of those patients would be identified and given care, Dr. Walensky and colleagues said, using the 350-cell threshold would result in 1,599,900 deaths compared with 1,622,000 for the lower level.

There would also be 1,664,500 opportunistic infections, compared with 1,689,700 using the lower threshold.

On the other hand, costs would increase by $141,977,100 (U.S.), they found.

At the other extreme, if all eligible patients were identified and linked to care, the higher threshold would avert 221,000 opportunistic diseases and 253,000 deaths.

The additional costs in that scenario would rise to $1.4 billion, the researchers said.

Either scenario would increase long-term survival by at least 7.9 years, with an average per-person life expectancy of 3.8 years with no therapy and 12.5 years at the 350-cell threshold.

Compared with the 250-cell threshold, starting at 350 had an incremental cost-effectiveness ratio of $1,200 per year of life saved, the researchers said.

“It is probably both effective and cost-effective” to allow therapy to start at the higher level, the researchers said.

Primary source: Annals of Internal Medicine

Source reference:

Walensky RP et al. “When to Start Antiretroviral Therapy in Resource-Limited Settings” Ann Intern Med 2009; 151.

CAPE TOWN, South Africa, July 24 — Men infected with human papillomavirus have an 80% increase in the risk of getting HIV, a researcher said here.

• Explain to interested patients that many sexually transmitted diseases are known to increase the risk of getting HIV.
• Note that this study found that infection with human papillomavirus, responsible for cervical cancer in women, is associated with and increased risk of getting HIV in men.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The finding comes from analysis of data collected during the landmark trial of male circumcision in Kisumu, Kenya, according to Jennifer Smith, PhD, of the University of North Carolina Chapel Hill.

That study showed that circumcision reduced the risk of getting HIV by more than 50%, Dr. Smith noted at the 2009 International AIDS Society conference.

But as part of the study, researchers also collected data regarding other sexually transmitted diseases, including human papillomavirus (HPV), she said in a late-breaker session in the final day of the conference.

“Many (sexually transmitted infections) have been previously found to be associated with increased risk of HIV infection,” Dr. Smith said. “However, surprisingly few data are available currently on any potential effect of HPV on HIV acquisition risk.”

To help fill the gap, she and colleagues studied participants in the Kisumu trial, looking at the 42-month risk of HIV seroconversion among men positive for HPV at the start of the study, compared with those who were not.

The study had data on HPV status for 2,168 men, including 1,089 who had the virus at baseline. Of those, 754 had high-risk strains of HPV (those that cause cancer in women) and 335 had low-risk strains.

Samples were taken from the penile shaft and foreskin, and from the glans and coronal sulcus, Dr. Smith said. The researchers controlled for the effect of circumcision, the main intervention in the study.

It turned that that only positive samples from the glans were associated with increased risk of HIV, she said.

For those men, the risk of getting HIV over the study period was 5.8%, compared with 3.7% for men whose glans samples were negative at baseline. The difference was significant at P=0.01.

The acquisition rates translated into a hazard ratio of 1.8 (95% CI 1.1 to 2.9), Dr. Smith said. (In contrast, the hazard ratio for positive samples collected from the shaft was 1.1, but the confidence interval crossed unity.)

The type of HPV isolated (high- or low-risk) was not associated with any difference in the chance of getting HIV.

Dr. Smith said more research is needed to explain the increase in risk. Possible explanations, she said, include residual confounding because of sexual behavior, or some sort of biological mechanism.

For instance, she said, the HPV virus might induce local cytokines, such as macrophage inflammatory protein-3 and interleukin-8, which play a role in susceptibility to HIV.

Or, the immunological process of clearing an HPV infection might bring increased numbers of CD4-positive T cells — the targets of HIV — to sites where they could be infected, she said.

The association “could be a marker for (risky) sexual behavior,” said Timothy Farley, PhD, of the World Health Organization’s reproductive health department, who chaired the session at which the research was presented.

Whatever the case, he said, it’s interesting to theorize that the process of clearing the papillomavirus — which can occur repeatedly — may have immunological consequences that increase susceptibility to HIV.

“It’s speculation as to what the mechanism might be, but it’s an intriguing one,” he said.

Whether a vaccine approach might affect the risk is also up in the air, he said, noting that current vaccines target the high-risk, cancer-causing strains of HPV, while Dr. Smith’s study showed no difference in HIV risk based on the HPV strain involved.

Dr. Farley noted that another circumcision trial, conducted in South Africa, had also showed an increased HIV risk for men infected with HPV.

Primary source: IAS Conference on HIV Pathogenesis and Treatment

Source reference:
Smith JS et al. “Risk of HIV acquisition among men with and without human papillomavirus infection in Kisumu, Kenya” IAS 2009; abstract WELBC104.

TORONTO, July 16 — Circumcision lowers the risk of getting HIV for men but doesn’t stop them from passing it on to women once they’re infected, researchers said.

• Explain to interested patients that three major clinical trials have demonstrated that circumcision reduces the risk that men will acquire HIV.
• Note that this study, on the other hand, said that circumcision does not prevent men from passing the virus on to their female partners once they have acquired HIV.

That’s the result of a randomized, controlled trial in Rakai, Uganda, that was run in parallel with one of the clinical trials that established the protective effect of circumcision for men, according to Maria Wawer, MD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues.

The trial was stopped early because its data safety monitoring committee said there was little chance continuing would demonstrate a benefit, Dr. Wawer and colleagues wrote in the July 18 issue of The Lancet.

The finding was disappointing because it contradicted previous observational studies which suggested that partners of circumcised HIV-positive men had a lower risk of getting HIV than women whose infected partners were not circumcised, the researchers said.

Early results of the trial were presented in Boston at the 2008 Conference on Retrovir uses and Opportunistic Infections. (See CROI: Circumcising HIV-Positive Men Doesn’t Block Transmission)

The finding has implications for widespread circumcision programs now being implemented in Africa, Dr. Wawer and colleagues said. Despite the lack of benefit for uninfected partners, HIV-positive men should not be barred from such programs, they said.

Among other things, they said, barring HIV-positive men might result in stigmatization, and such men might then seek the procedure from unsafe sources in order to mask their infection.

The larger circumcision trial randomized men to immediate circumcision or waiting 24 months for the procedure. Those with delayed circumcision formed the control group.

This study enrolled HIV-negative female partners of men in the larger trial, including 93 women whose partners were in the intervention group and 70 with partners in the control group.

A modified intent-to-treat analysis included 92 couples in the intervention group and 67 couples in the control group. The researchers found:

• 17 women in the intervention group (or 18%) got HIV during follow-up, compared with eight women (or 12%) in the control group. The difference was not significant, at P=0.36.
• At 24 months, cumulative probabilities of female HIV acquisition were 21.7% in the intervention group and 13.4% in the control group. The adjusted hazard ratio was 1.49, with a 95% confidence interval from 0.62 to 3.57, which was not significant (at P=0.368).

In a subanalysis that was not part of the study’s original plan, the researchers found that early resumption of sexual intercourse after the procedure increased the risk of transmission.

Specifically, 27.8% of women whose partners were in the intervention group and who resumed sex early (more than five days before the wound was certified as completely healed) got HIV.

In contrast, only 9.5% of women with partners in the intervention group but who delayed sex acquired the virus.

“The possibility of higher risk of transmission in couples who resumed sexual intercourse before complete wound healing cannot be excluded,” the researchers said.

One implication of the research is that condom use after circumcision remains important, Dr. Wawer and colleagues said.

Indeed, “circumcision programs should make the most of the opportunity to provide condoms and risk-reduction counseling, and to offer voluntary HIV testing,” argued Jared Baeten, MD, of the University of Washington in Seattle, and colleagues.

In an accompanying comment article, they wrote that such counseling should emphasize the need to wait until healing is complete before resuming sexual intercourse.

And despite the lack of a direct effect, women will benefit from widespread circumcision, they said, because of decreased HIV prevalence and because circumcision will prevent some men from getting the virus and passing it on.

The investigators noted that “a higher proportion of female partners in the intervention group were enrolled in the study (78%) than were partners in the control group (69%, P=0.007). This finding suggests differential motivation to participate between trial groups, which could have introduced bias.”

They also pointed out that “for reasons of safety, we excluded HIV-infected men with CD4-cell counts less than 350 cells per ?L or with WHO clinical stage 3 or 4 disease. Thus, the current study cannot establish possible effects on female partners of circumcision in men with more advanced HIV infection.”

Primary source: The Lancet

Source reference:
Wawer MJ, et al “Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial” Lancet 2009; 374: 229-37.

Additional source: The Lancet

Source reference:
Baeten JM, et al “Male circumcision and HIV risks and benefits for women” Lancet 2009; 374:182-84.

Related Article(s):

• CROI: Circumcising HIV-Positive Men Doesn’t Block Transmission