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Durban, South Africa

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.

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.

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.

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.,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.

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