Antiretroviral prophylaxis: a defining moment in HIV control

A defining moment in the global AIDS response has been reached. The discourse is no longer about HIV prevention or HIV treatment; it is now about HIV control through the implementation of antiretrovirals as key components of combination interventions. Barely a year ago, visions of HIV control would have been considered far-fetched. The impetus for this change in mindset, which has been building since the XVIII International AIDS Conference in Vienna last year, emanates from the compelling evidence that antiretroviral drugs prevent HIV infection in the general heterosexual population, which is released this week and presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome by the Partners PrEP and Botswana TDF2 trials

AIDS research must link to local policy

HIV research in South Africa is world class. To halt the country's epidemic, scientists need to shift focus from global problems to priorities at home

Contraceptive Choices, Pregnancy Rates, and Outcomes in a Microbicide Trial

OBJECTIVE: Women who become pregnant during the conduct of biomedical human immunodeficiency virus prevention trials are taken off the study product for safety reasons. High pregnancy rates can compromise statistical integrity in these trials. The comprehensive contraceptive curriculum developed for the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial was evaluated for its ability to enhance contraceptive uptake, reduce pregnancy rates, and preserve statistical integrity. METHODS: Contraceptive- and pregnancy-related eligibility criteria were specified in the protocol. We enrolled women who opted for a nonbarrier method of contraceptive and provided hormonal contraceptives onsite at no cost. At each monthly study visit, we provided pregnancy prevention counseling and performed pregnancy testing. Study product was withheld on pregnancy diagnosis, but women continued with monthly follow-up. RESULTS: Contraceptive use was high throughout the study with 100% uptake at baseline and 94.71% use after a mean of 18 months follow-up at exit. Injectable progestins, particularly medroxyprogesterone acetate, remained the preferred choice of contraceptive. After 30 months of follow-up, 54 pregnancies were reported out of 889 participants, giving a pregnancy incidence rate of 3.95 per 100 woman-years (95% confidence interval 2.96-5.17). Of all pregnancies, two thirds (64.81%) resulted in a full-term live birth, whereas 18.52% and 11.11% pregnancies culminated as miscarriage and terminated pregnancies, respectively. There were no congenital anomalies in the early neonatal period. Pregnancies resulted in 1.56% of woman-years of study follow-up lost as a result of temporary product withdrawal. CONCLUSION: The CAPRISA 004 contraceptive curriculum was an effective strategy for maintaining low pregnancy rates, thereby minimizing product withdrawal and loss of follow-up time

Design challenges facing clinical trials of the effectiveness of new HIV prevention technologies

Recent successes of antiretroviral pre-exposure prophylaxis (PrEP) in preventing HIV infection have raised questions whether further placebo controlled trials of new HIV-prevention technologies are ethically justifiable. A trial with active agent(s) in the comparator group can be designed either as a superiority or non-inferiority trial. In a non-inferiority trial the hypothesis tested is that the intervention is not inferior to, by a predefined clinically relevant amount, or at least as effective as, the comparator. Non-inferiority trials pose challenges in data interpretation.Firstly it is possible to show equivalence of two non-effective interventions. If the active comparator intervention is ineffective, the new intervention would be shown to be non-inferior to this inactive intervention, while neither intervention is superior to placebo or no intervention. The second challenge is that any effect that dilutes the true efficacy of an intervention in a trial, such as non-adherence, loss to follow-up or protocol violations, makes it easier for the two interventions to be declared equivalent. Non-differential low adherence is unlikely to lead to the conclusion that an inferior intervention is non-inferior. However, differential adherence between study arms, which is more likely in non-blinded trials, is likely to bias the results and lead to incorrect conclusions. Investigators conducting non-inferiority trials will have to pay special attention to supporting, measuring and maintaining high adherence. The goal in future non-inferiority trials should be to maintain similar levels of high adherence in all study arms, but at a minimum to reduce the likelihood of differential adherence across study arms

Results of effectiveness trials of PRO 2000 gel: lessons for future microbicide trials

Despite numerous scientific, ethical and methodological challenges, microbicides provide real potential to influence the course of the HIV epidemic as they could fill an important gap for women-initiated prevention methods

Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women

The early closure of a clinical trial assessing the effectiveness of oral antiretroviral pre-exposure prophylaxis (PrEP) in women, FEM-PrEP, is a substantial setback for HIV prevention. Expectations of this trial were high in view of favourable results from the pre-exposure prophylaxis initiative (iPrEX) trial, which studied the same drug and dosing strategy in men who have sex with men, and the Centre for the AIDS Programme of Research in South Africa (CAPRISA 004) trial,3 which tested tenofovir gel (a topical PrEP formulation) in heterosexual women. As a result, the interim FEM-PrEP trial results, announced on April 18, 2011, which showed no protection against HIV infection, were disappointing. Using publicly available information and data from other PrEP studies, we offer a potential explanation for the results of the FEM-PrEP trial

Underreporting and overreporting of hepatitis B at a tertiary hospital

Objective. To assess the level of underreporting and overreporting of hepatitis B infection at a tertiary hospital.Design. Retrospective record review.Setting. King Edward VIII Hospital, Durban.Main outcome measures. Hepatitis B notification was assessed. Underreporting was ascertained on the basis of the proportion of hepatitis B-positive laboratory results that were not notified. Overreporting was indicated by duplication of notifications and the reporting of patients who have not tested positive for hepatitis B.Results. 83.7% (95% confidence interval 79.4 - 88.0%) of patients with hepatitis B virus infection were not reported. no hospital outpatients were reported and 6% (95% confidence interval 0 - 12.6%) of the reported hepatitis B cases were not hepatitis B.Conclusion. Underreporting of hepatitis B virus infection is the result of an inadequate notification system at a health institution level. A new, user-friendly system of surveillance that actively monitors the reporting rate is recommended to improve the reporting rate and thus generates useful information

Stigma impedes AIDS prevention

Thirty years since the first cases of AIDS were described, there is much to celebrate regarding progress in the treatment and prevention of the disease. Within the past year alone, several studies have revealed that antiretroviral drugs can prevent the sexual transmission of HIV. Yet worldwide, many people who are potentially exposed to the virus avoid finding out whether they carry it, or deny that they are at risk of contracting it. Unless people establish whether they are infected, they will not be able to be adopt the most appropriate preventive measures. As scientists and clinicians, our ability to overcome this denialism will determine whether we ultimately succeed in using combinations of all the preventive and therapeutic tools now available to slow, and eventually stop, the HIV/AIDS pandemic

Medical education after the first decade of democracy in South Africa.

No abstract available

Assessing progress with HIV incidence in national cohorts.

CAPRISA., 2017.Abstract available in pdf