HIV prevention Research Unit

Durban, South Africa

HIV prevention Research Unit

Durban, South Africa
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Marrazzo J.M.,University of Washington | Ramjee G.,HIV Prevention Research Unit | Richardson B.A.,Fred Hutchinson Cancer Research Center | Gomez K.,FHI 360 | And 23 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS: Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 personyears. In the modified intention-to-treat analysis, the effectiveness was-49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29),-4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. Copyright © 2015 Massachusetts Medical Society.

Mayer K.H.,Beth Israel Deaconess Medical Center | Ramjee G.,HIV Prevention Research Unit | Ramjee G.,London School of Hygiene and Tropical Medicine
Current Opinion in HIV and AIDS | Year: 2015

Purpose of review This review was designed to evaluate the progress in studies of the use of oral and topical antiretroviral (ARV) medication for primary HIV prevention. Recent findings Nonhuman primate data have suggested that the administration of ARV medication before or after retroviral exposure can protect against the establishment of chronic infection. Over the past two decades, observational studies have demonstrated the safety of ARV agents for postexposure prophylaxis and more recent efficacy studies have demonstrated that tenofovir with or without emtricitabine can protect against HIV when used as preexposure prophylaxis (PrEP). Efficacy studies have been conducted in diverse populations, including men and transgender women who have sex with men, young African heterosexuals, and injection drug users. Three studies in African women evaluating oral and topical tenofovir-based regimens did not demonstrate efficacy, in large part because of suboptimal medication adherence. Further research is underway to determine the optimal ways to provide chemoprophylaxis, the optimal medications, and dosing regimens. Summary PrEP can be effective in decreasing HIV transmission to at-risk uninfected persons, but further research is needed to determine the optimal modes of delivery. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Ramjee G.,HIV Prevention Research Unit | Ramjee G.,London School of Hygiene and Tropical Medicine
Current Opinion in HIV and AIDS | Year: 2010

PURPOSE OF REVIEW: Microbicide research has been in the forefront of scientific literature in recent months. Results of large-scale clinical trials have been announced with resultant investigations into the factors that may have contributed to the disappointing outcomes of the most promising candidates. This review takes into consideration clinical, basic scientific and behavioural research published on microbicides in the past 12-18 months. RECENT FINDINGS: Two trials testing PRO 2000, a sulphated polymer, suggested that it has no effect on HIV. Basic science research revealed several facts such as the loss of antiviral activity of microbicides in the presence of seminal plasma. Methodological models suggested that dilution factors might impact on measures of efficacy. Advancement into safety testing of highly specific antiretroviral products such as tenofovir and UC781 for both rectal and vaginal use shows promise. Development of drug delivery systems such as intravaginal rings may alleviate some of the adherence challenges faced when using coitally dependant products. SUMMARY: In the recent past, microbicide research has had disappointing outcomes. However, it has also provided a better understanding of factors that may reduce effectiveness of promising products, enabling the field to be better equipped to select and test new products. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Wand H.,University of New South Wales | Ramjee G.,HIV Prevention Research Unit
AIDS and Behavior | Year: 2012

Semiparametric regression models based on smoothing splines were used to examine the associations between the risk of HIV seropositivity and a continuous covariate. For example, in the fully parametric logistic regression model, age was associated with a decreased risk of HIV seropositivity [Odds ratio (OR): 0.94 per 5 year increase, 95% Confidence Interval (CI): 0.90-0.98]. This association was not evident when the age was dichotomized at the median [i.e. >26 years vs. ≤26 years (reference)] (OR: 1.06, 95% CI: 0.92-1.21). Understanding the relationship between a continuous covariate and an outcome variable of interest involves determining the shape and strength of that relationship. The choice of the most appropriate approach depends on the specific problem and available data. We showed that using semiparametric regression techniques may be helpful in understanding the best way to do the categorization when it is desired. © 2011 Springer Science+Business Media, LLC.

Wand H.,University of New South Wales | Ramjee G.,HIV Prevention Research Unit
BMJ Open | Year: 2012

Objectives: To investigate the impact of early sexual debut on HIV seroprevalence and incidence rates among a cohort of women. Design: Prospective study. Setting: KwaZulu-Natal, South Africa. Participants: A total of 3492 sexually active women who consented to screen a HIV prevention trial during September 2002 to September 2005; a total of 1485 of them were followed for approximately 24 months. Primary and secondary outcome measures: HIV seroprevalence among those who were screened for the trial and HIV seroconversion among those who seroconverted during the study. Results: Lowest quintiles of age at sexual debut, less than high school education, a higher number of lifetime sexual partners and lack of cohabitation, being diagnosed as having herpes simplex virus 2 and other sexually transmitted infections were all significantly associated with prevalent HIV infection in multivariate analysis. During follow-up, 148 (6.8 per 100 personyears, 95% CI 5.8 to 8.0) women seroconverted. Highest seroconversion rate was observed among women who had reported to have had sex 15 years or younger (12.0 per 100 person-years, 95% CI 8.0 to 18.0). Overall, impact of risk factors considered in this study was associated with considerable potential reductions in HIV prevalence and incidence rates (population attributable risk: 85%, 95% CI 84% to 87% and population attributable risk: 77%, 95% CI 72% to 82%, respectively). Conclusions: The association of HIV status with younger age at sexual debut may likely due to an increased number of lifetime partners. This increase could result from longer duration of sexual life. Prevention of HIV infection should include efforts to delay age at first sex in young women.

Background: In South Africa, poverty and the dual epidemics of HIV and tuberculosis underscore the need for prevention efforts for obesity. The aim of this study was to describe the prevalence of obesity in a cohort of South African women and discuss the implications for public health practices. Methods. A total of 5,495 HIV-negative women from KwaZulu-Natal, South Africa enrolled in three microbicide trials during the period of 2002-2008 were categorised as normal weight (body mass index (BMI: 18.6-<25), overweight (BMI: 25-<30) or obese (BMI: 30+). Incidence of HIV and other sexually transmitted infections such as Chlamydia and gonorrhoea were also estimated and compared by BMI groups. Combined data was analysed using STATA 10.0. Results: Approximately 70% of the sample population was classified as being overweight or obese. Older age and lack of education were determined to be significant predictors of obesity. Women who were 35years or older were more than three times as likely to be overweight and more than 12 times as likely to be obese compared to the youngest group. The highest HIV and STI incidence rates were observed among those with BMI <25kg/m2 (normal weight) compared to women with BMI more than 25kg/m2 (8.1 and 19.8 per 100 person-year respectively, P<0.001, both). Conclusion: Effective obesity prevention strategies are needed to re-formulate HIV prevention programmes by incorporating healthy diet and life style messages to target those who are at highest risk not just for HIV infection but also for non-communicable diseases. © 2013 Wand and Ramjee; licensee BioMed Central Ltd.

Wand H.,University of New South Wales | Ramjee G.,HIV Prevention Research Unit
AIDS | Year: 2012

Objectives: To investigate the association between hormonal contraceptives and risk of HIV-1 seroconversion and prevalence of other sexually transmitted infections. Design: Prospective cohort. Methods: The study population was 2236 HIV-negative women who were screened in a biomedical intervention trial in Durban, South Africa. The association between the use of hormonal contraceptives and risk of HIV-1 seroconversion was modeled using Cox proportional hazards regression analysis. Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections were assessed using logistic regression models. Results: Hormonal injectables were the most common method of contraceptives (46.47%) followed by condom use (28.04%). Overall, compared with women who reported using condoms or other methods as their preferred form of contraceptive, those who reported using hormonal contraceptives (injectables and oral pills) were less likely to use condoms in their last sexual act. Using hormonal injectables during the study was significantly associated with increased risk for HIV-1 infection [adjusted hazard ratio 1.72, 95% confidence interval (CI) 1.19-2.49, P=0.005]; hormonal injectables were also significantly associated with higher prevalent of C. trachomatis infections (adjusted odds ratio 2.46, 95% CI 1.52-3.97, P<0.001). Conclusion: Hormonal injectables are highly effective and well tolerated family planning methods and have played an important role in reducing unplanned pregnancies and maternal and infant mortality. However, they do not protect against HIV-1 and other sexually transmitted infections. This study reinforces the importance of comprehensive contraceptive counseling to women about the importance of dual protection, such as male condoms and hormonal contraceptives use. © 2012 Wolters Kluwer Health Lippincott Williams & Wilkins.

Ramjee G.,HIV Prevention Research Unit | Kamali A.,HIV Prevention Research Programme | McCormack S.,Medical Research Council Clinical Trials Unit
AIDS | Year: 2010

Microbicide clinical trials have dominated biomedical HIV prevention research in the past decade. Two generations of microbicides have gone through large-scale human clinical trials. Candidate microbicides assessed in clinical trials in Africa have fallen into the categories of surfactants, polyanionic entry inhibitors, or vaginal milieu protectors. These include compounds such as nonoxynol-9, SAVVY, cellulose sulphate, Carraguard, PRO 2000, and BufferGel. Disappointingly, none of the products have shown efficacy against HIV. Each successive trial has benefited from the lessons learned in preceding trials. The trials have provided important lessons in basic, clinical, social, and behavioural science. More importantly, we have learned that the concept of a vaginally inserted product for HIV prevention is acceptable by women. We have now reached an end of an era of clinical testing with non-HIV-specific microbicides and move forward to testing novel strategies of antiretroviral therapeutic products such as preexposure prophylaxis (PrEP) for HIV prevention. PrEP for vaginal administration in various formulations is being tested to continue our commitment to providing more HIV prevention options to millions of women worldwide. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Wand H.,National Center in Epidemiology and Clinical Research | Ramjee G.,HIV Prevention Research Unit
Journal of the International AIDS Society | Year: 2010

Background. In South Africa, the severity of the HIV/AIDS epidemic varies according to geographical location; hence, localized monitoring of the epidemic would enable more effective prevention strategies. Our objectives were to assess the core areas of HIV infection in KwaZulu-Natal, South Africa, using epidemiological data among sexually active women from localized communities. Methods. A total of 5753 women from urban, peri-rural and rural communities in KwaZulu-Natal were screened from 2002 to 2005. Each participant was geocoded using a global information system, based on residence at time of screening. The Spatial Scan Statistics programme was used to identify areas with disproportionate excesses in HIV prevalence and incidence. Results. This study identified three hotspots with excessively high HIV prevalence rates of 56%, 51% and 39%. A total of 458 sexually active women (19% of all cases) were included in these hotspots, and had been exclusively recruited by the Botha's Hill (west of Durban) and Umkomaas (south of Durban) clinic sites. Most of these women were Christian and Zulu-speaking. They were also less likely to be married than women outside these areas (12% vs. 16%, p = 0.001) and more likely to have sex more than three times a week (27% vs. 20%, p < 0.001) and to have had more than three sexual partners (55% vs. 45%, p < 0.001). Diagnosis of genital herpes simplex virus type 2 was also more common in the hotspots. This study also identified areas of high HIV incidence, which were broadly consistent with those with high prevalence rates. Conclusions. Geographic excesses of HIV infections at rates among the highest in the world were detected in certain rural communities of Durban, South Africa. The results reinforce the inference that risk of HIV infection is associated with definable geographical areas. Localized monitoring of the epidemic is therefore essential for more effective prevention strategies - and particularly urgent in a region such as KwaZulu-Natal, where the epidemic is particularly rampant. © 2010 Wand and Ramjee; licensee BioMed Central Ltd.

Wand H.,National Center in Epidemiology and Clinical Research | Whitaker C.,HIV Prevention Research Unit | Ramjee G.,HIV Prevention Research Unit
International Journal of Health Geographics | Year: 2011

Background: The severity of the HIV/AIDS epidemic in South Africa varies between and within provinces, with differences noted even at the suburban scale. We investigated the geographical variability of HIV infection in rural areas of the eThekwini Metropolitan Municipality in KwaZulu-Natal province, South Africa.Method: We used geoadditive models to assess nonlinear geographical variation in HIV prevalence while simultaneously controlling for important demographic and sexual risk factors. A total of 3,469 women who were screened for a Phase-III randomized trial were included in the current analysis.Results: We found significant spatial patterns that could not be explained by demographic and sexual risk behaviors. In particular, the epidemic was determined to be much worse 44 km south of Durban after controlling for all demographic and sexual risk behaviors.Conclusion: The study revealed significant geographic variability in HIV infection in the eThekwini Metropolitan Municipality in KwaZulu-Natal, South Africa. © 2011 Wand et al; licensee BioMed Central Ltd.

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