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

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

Public-private health sector partnerships for STD control in South Africa perspectives from the Hlabisa experience

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SARS-CoV-2 variants and ending the COVID-19 pandemic

International audienc

Recent Semen Exposure Impacts the Cytokine Response and Bacterial Vaginosis in Women

BackgroundThe presence of semen in the vagina from unprotected sex may influence the immune and microbial environment of the female genital tract. Inflammatory cytokine concentrations and BV-associated bacteria in female genital secretions may influence HIV risk, although the effect of recent sexual intercourse on incident BV and the cytokine milieu of cervicovaginal secretions has rarely been measured in previous studies. Here, we investigated the extent to which partner semen impacts the cytokine response and incident BV.MethodsAt baseline, we assessed the recency of semen exposure in menstrual cup supernatants by quantifying prostate specific antigen (PSA) levels using ELISA in 248 HIV-uninfected women at high risk for HIV infection. Luminex was used to measure 48 cytokines in menstrual cup supernatants and vaginal swabs to diagnose BV by Nugent score. Point-of-care screening for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted using GeneXpert while OSOM was used for Trichomonas vaginalis detection. Multivariable models, adjusted for age, sexually transmitted infections, BV, current contraception use and condom use, were used to assess the impact of semen exposure on biomarkers of inflammation and BV.ResultsPresence of PSA, indicating recent semen exposure within 48 hours prior to sampling, was observed in menstrual cup supernatants of 17% (43/248) of women. Of these women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had BV (Nugent score >7). PSA presence was significantly associated with prevalent BV (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029). Furthermore, women with detectable PSA had high median concentrations of macrophage inflammatory protein- beta (MIP-1α, p=0.047) and low median concentration of the stem cell growth factor beta (SCGF-β, p=0.038) compared to those without PSA.ConclusionA degree of discordance between self-reports of consistent condom use and PSA positivity was observed. There was also evidence of a relationship between recent semen exposure, BV prevalence and altered cytokine concentrations. These findings suggest that PSA, as a semen biomarker, should be taken into consideration when investigating biological markers in the female genital tract and self-reported condom use in studies on reproductive and sexual health

Ratio of monocytes to lymphocytes in peripheral blood identifies adults at risk of incident tuberculosis among HIV-infected adults initiating antiretroviral therapy.

Background. Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases. Methods. The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted. Results. The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4⁺ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002). Conclusions. The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis

Enrolling adolescents in research on HIV and other sensitive Issues: lessons from South Africa.

The article discusses the challenge of enrolling adolescents in HIV studies in South Africa. It is practically impossible in some instances to seek parental consent or to determine who, if anyone, is the legal guardian to authorize an adolescent's participation in research. The South African Medical Research Council research ethics guidelines prescribe 14 years of age as the autonomous age of consent for therapeutic research but not observational studies

Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression

BACKGROUND: Both T-cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown. OBJECTIVES: To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression. DESIGN: Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection. METHODS: The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set point 12 months postinfection and time taken for CD4 cell counts to fall below 350 cells/microl were determined using multivariate and Cox proportional hazards regression. RESULTS: We found that the concentrations of five plasma cytokines, IL-12p40, IL-12p70, IFN-gamma, IL-7 and IL-15 in women with acute infection predicted 66% of the variation in viral load set point 12 months postinfection. IL-12p40, IL-12p70 and IFN-gamma were significantly associated with lower viral load, whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and granulocyte-macrophage colony-stimulating factor during acute infection were associated with maintenance of CD4 cell counts above 350 cells/microl, whereas IL-1alpha, eotaxin and IL-7 were associated with more rapid CD4 loss. CONCLUSION: A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women