Kristin N. Harper

Two recent studies find Depo-Provera use increases HIV risk.

Depo-Provera (DMPA), a shot given every 3 months, is the most widely used hormonal contraceptive in subSaharan Africa. Recently, two meta-analyses focusing on sub-Saharan Africa have concluded that DMPA use increases HIV risk. The first study, by Lauren Ralph of the University of California at San Francisco and colleagues, included 12 studies and found that women using DMPA were roughly 40% more likely to contract HIV than women who used nonhormonal contraceptives or no contraceptives (Lancet Infect Dis 2015; 15 : 181–189). The second study, by Charles Morrison of FHI 360 and colleagues, analysed data from 18 studies – eight of which had not previously assessed the relationship between hormonal contraceptives and HIV – and found that women using DMPA were 50% more likely to contract HIV than those who did not use a hormonal form of birth control and roughly 40% more likely than combined oral contraceptive users (PLoS Med 2015; 12:e1001778). ‘The similarity in our findings is striking’, says Ralph, pointing out that her study used pooled individual study estimates, while the study by Morrison et al. used individual participant data. In addition, only eight studies were included in both analyses, so different women contributed to their estimates.

Simplified HIV testing and treatment reduces mortality rate by over 60% in a trial in China.

In a recent article in PLoS Medicine (2015; 12:e1001874), Zunyou Wu of the Chinese Center for Disease Control and Prevention and colleagues presented the results of an intervention to simplify HIV diagnosis and treatment in two Chinese counties. Wu explains that the study was motivated by the high number of patients in some areas who were being diagnosed at an advanced stage of disease and dying in the same year; the goal was to intervene in the months between diagnosis and death. In the target counties, patients who screened positive for HIV infection received rapid testing, and antiretroviral therapy (ART) was initiated immediately upon receiving a positive result, irrespective of CD4þ cell count. This reduced the average time from HIV confirmation to ART initiation from around 50 to 5 days and increased the percentage of patients who initiated ART from below 36% to above 90%. Most importantly, this intervention reduced mortality rates by 62%. Wu says the lesson to draw from this dramatic improvement is to ‘look at AIDS as a reality and pragmatically analyze how to provide simplified services for patients’.

A decade of learning about the HIV reservoir: new insights into latent infection

One longstanding question is how cells become latently infected. In 2007, Suha Saleh (Monash University, Australia) and colleagues published an article that provided one of the first pieces of the puzzle. They demonstrated that when resting CD4+ T cells are incubated with certain chemokines and then infected with HIV, many copies of the virus are able to integrate into the cells’ genomes. [1] Sharon Lewin (University of Melbourne), the senior author of the article, observes that this study “was the first to show that latency

Preexposure prophylaxis on-demand dramatically reduces HIV incidence in MSM.

Recently, multiple clinical trials have shown that preexposure prophylaxis (PrEP) is an effective means of preventing HIV infection – but only if individuals adhere to the treatment, which involves a daily dose of drugs. In a recent issue of the New England Journal of Medicine (2015; 373: 2237–2246), Jean-Michel Molina of the Hôpital Saint-Louis and colleagues reported the results of IPERGAY, a randomized controlled trial that assessed a different PrEP dosage system: two pills 2–24 h before sex, a third pill 24 h after the first pill, and a fourth pill 24 h after that. In MSM, the group being studied, this treatment was associated with an 86% reduction in new HIV infections, one of the largest reported to date for PrEP. Jared Baeten of the University of Washington comments, ‘While the Molina et al. results are just one study, they are pretty powerful and are backed up by animal model data that suggested an on-demand approach would work in the first place.’ Cécile Tremblay of the Université de Montréal observes, ‘We have already seen an effect of the IPERGAY results on PrEP uptake. These results validated the efficacy of PrEP and increased confidence in both patients and doctors that the approach was effective. On-demand PrEP gives more flexibility and options to patients.’

No changes in sexual behaviour after voluntary medical male circumcision in the Dominican Republic.

Multiple trials have demonstrated that voluntary medical male circumcision (VMMC) has a protective effect against HIV infection. These studies have been conducted in sub-Saharan Africa, however, leading some to question whether the same effects would be observed elsewhere, and one frequently raised concern is that circumcision may lead men to adopt riskier behaviours out of a false sense of security. At IDWeek 2015, Maximo Brito of the University of Illinois College of Medicine and colleagues presented data from a study conducted in the Dominican Republic. This study involved 454 men who underwent VMMC, 80% of whom returned for a follow-up visit 6–8 months after their surgery, at which time data about their sexual behaviour, penile trauma after intercourse and their satisfaction with the circumcision were collected and compared with data gathered prior to the surgery. After circumcision, no changes in condom use or the number of female partners in the past 6 months were reported, and there was a significant decrease in the number of men who reported having sex with a woman they met on the same day. Thus, there was no evidence of risk compensation. In addition, 98% of men reported they were either ‘very satisfied’ or ‘somewhat satisfied’ with their circumcision, and the prevalence of penile trauma after intercourse significantly decreased. Brito concludes, ‘The big takeaway from this study is that VMMC programs can be exported to settings outside of Africa, men’s satisfaction with their sexual life after the procedure is quite high, and it dramatically improves penile trauma’. Noting the relatively large sample size, he also points out that the study shows that men in this

The emergence of acquired HIV-1 drug resistance has nearly stopped in Switzerland.

Alexandra Scherrer from University Hospital Zürich and colleagues recently published an article in Clinical Infectious Diseases (2016; 62 : 1310–317) on the near disappearance of acquired drug resistance in Switzerland. Their study followed 11 094 antiretroviral therapy (ART)-experienced patients from 1999 to 2013. During that period, the emergence of new drug resistance mutations declined from 401 in 1999 to 23 in 2013, and at the end of the study nearly 95% of patients who had initiated ART before 1999 still had good remaining treatment options. Coauthor Huldrych Günthard, also of University Hospital Zürich, says that these findings show that ‘it is possible on the population level to halt the emergence of drug resistance in HIV-treated patients under the best possible circumstances: unrestricted access to healthcare, availability of all drugs for all people, systematic monitoring, and baseline resistance testing’.