Single daily poly-pill for HIV

In a prospective, randomized trial, a single daily tablet containing efavirenz, emtricitabine, and tenofovir (Atripla; Bristol Myers Squibb & Gilead Sciences LLC) maintained viral suppression in HIV-1 infected patients as well as the standard multiple-pill regimen.

The report of the study, published in the Journal of the Acquired Immune Deficiency Syndrome, notes that at baseline, all 300 participants were on stable antiretroviral therapy (ART) regimens, with viral loads of less than 200 copies/mL for at least 3 months. Their mean CD4 count was 540 cells/�L, and 96% of subjects had HIV-1 RNA <50>

On randomization, 203 were assigned to the Atripla regimen while 97 remained on their baseline regimen. The entire 48-week study was completed by 266 patients.

In the intent-to-treat analysis, it was found that at 48 weeks, the primary endpoint -- HIV-1 RNA below 200 copies/mL -- had been achieved by 89% of the patients in the single-tablet group versus 88% of those on unmodified antiretroviral regimens, "indicating noninferiority" of the newer approach.

Similarly, there was no significant difference between groups in maintenance of viral load below 50 copies/mL and no significant changes in CD4 cell counts within or between the two arms of the study.

Discontinuation rates were similar between the groups, but more patients in the single-tablet group discontinued due to adverse events, "most commonly for nervous system symptoms," according to the investigators.

Three patients in the single-tablet group and one in the control group had virologic failure.

"In summary," the researchers conclude, "patients who were stable and virologically suppressed while receiving a wide array of non-nucleoside reverse transcriptase inhibitor- and protease inhibitor-based antiretroviral regimens and had their treatment simplified to a single-tablet regimen of efavirenz, emtricitabine, and tenofovir maintained high rates of virologic suppression compared to those who continued their regimen unmodified."

Source: J Acquir Immune Defic Syndr 2009;51:163-174.

Circumcision reduced the incidence of human immunodeficiency virus (HIV), HSV 2, HPV infections

Male circumcision significantly reduced the incidence of HIV and herpes simplex virus type 2 (HSV-2) infection and the prevalence of human papillomavirus (HPV) infection, suggesting potential public health benefits, according to the results of a randomized controlled trial reported in the March 26 issue of the New England Journal of Medicine.

"Male circumcision significantly reduced the incidence of...HIV infection among men in three clinical trials," write Aaron A.R. Tobian, MD, PhD, from Bloomberg School of Public Health, Johns Hopkins University in Baltimore, Maryland, and colleagues. "We assessed the efficacy of male circumcision for the prevention of...HSV-2 and...HPV infections and syphilis in HIV-negative adolescent boys and men."

Two trials of male circumcision to prevent HIV and other sexually transmitted infections in a rural Ugandan population enrolled a total of 5534 HIV-negative, uncircumcised male subjects aged 15 to 49 years. Of 3393 subjects (61.3%) who were HSV-2 seronegative at enrollment, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). Subjects were tested for HSV-2 and HIV infection and syphilis and underwent physical examinations and interviews at baseline and at 6, 12, and 24 months. A subgroup of subjects was also evaluated for HPV infection at baseline and at 24 months.

The cumulative probability of HSV-2 seroconversion by 24 months was 7.8% in the intervention group vs 10.3% in the control group. High-risk HPV genotypes were present at 24 months in 18.0% of the intervention group vs 27.9% of the control group.

"In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure," the study authors write. "These findings, in conjunction with those of previous trials, indicate that circumcision should now be accepted as an efficacious intervention for reducing heterosexually acquired infections with HSV-2, HPV, and HIV in adolescent boys and men. However, it must be emphasized that protection was only partial, and it is critical to promote the practice of safe sex."

Points to remember

• Uncircumcised men may be at higher risk for sexually transmitted infection because of greater exposure of the lightly keratinized inner preputial mucosa during intercourse, a higher risk for microtears, and a favorable environment in the subpreputial cavity for incubation of infection.
• In the current study, circumcision reduced the risk for infection with HSV-2 and HPV

(ClinicalTrials.gov numbers, NCT00425984 [ClinicalTrials.gov] and NCT00124878 [ClinicalTrials.gov] .)

Aaron A.R. Tobian et al. Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis. New England Journal of Medicine. 360 (13) :1298-1309, March 26, 2009