Biomedical subjects

Gita Ramjee

Publications and source records attributed to Gita Ramjee.

13 recordsLinked to original sources

PubMed2006

Microbicides 2006 conference.

Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23-26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities.

Journal Article↗

PubMed2006

The impact of the use of COL-1492, a nonoxynol-9 vaginal gel, on the presence of cervical human papillomavirus in female sex workers.

This study investigated the effectiveness of a nonoxynol-9 (52.5mg, 3.5%), vaginal gel (Advantage S), in the prevention of human papillomavirus (HPV) infection in female sex workers. We showed by HPV DNA determination in cervico-vaginal rinses a significant increase in multiple (>1) HPV infection in HIV-1 seropositive women compared with HIV-1 seronegative women (OR 4.0, 95% CI 1.3-11.9). We also demonstrated a significant increase in multiple HPV infections in HIV-1 seronegative women using nonoxynol-9 compared with HIV-1 seronegative women using placebo (OR 3.5 95% CI 1.0-11.8). We conclude that the use of nonoxynol-9 did not prevent genital HPV infection and could increase the virus' ability to infect or persist.

Administration, Intravaginal↗

PubMed2006

"We have our protector": misperceptions of protection against HIV among participants in a microbicide efficacy trial.

OBJECTIVES: We examined perceptions of the effectiveness and acceptability of a candidate microbicide among 94 South African female sex workers who had participated in a phase 3 microbicide trial for HIV prevention. METHODS: Sixteen focus groups were conducted in 2001, 12 to 15 months after participants were informed that the candidate microbicide had been determined to be ineffective in preventing HIV and other sexually transmitted infections (STIs). RESULTS: Participants clearly indicated that they understood the experimental nature of the candidate microbicide, and they recognized that they had been informed after the trial that the product was ineffective. Nevertheless, most continued to believe that the candidate microbicide helped prevent HIV and other STIs, alleviated reproductive tract pain and STI symptoms, and helped to clean the vagina. CONCLUSIONS: These findings underscore the importance of understanding women's perceptions of the efficacy of candidate microbicides and the rationale for these beliefs. These issues need to be addressed in counseling throughout microbicide trials for HIV prevention. These results also demonstrate how desperate many women at high risk of HIV infection may be for new HIV prevention technologies.

Adolescent↗

PubMed2005

The impact of incident and prevalent herpes simplex virus-2 infection on the incidence of HIV-1 infection among commercial sex workers in South Africa.

This study investigated the impact of prevalent and incident HSV-2 infection on the incidence of HIV-1 infection in a cohort of female commercial sex workers in KwaZulu-Natal, South Africa. Prior to a vaginal microbicide trial, 416 women were screened for antibodies to HIV-1 and herpes simplex virus-2 (HSV-2) infections and a questionnaire was used to establish behavioral, social, and demographic characteristics. A total of 187 HIV-1-seronegative women were followed up at monthly intervals when blood was drawn and used to detect HIV-1 and HSV-2 antibodies. The median duration of follow-up was 2.2 years. At screening 50% of the women were HIV-1 seropositive and 84% were HSV-2 seropositive. The hazards of HIV-1 among women who were HSV-2 seropositive or seronegative throughout, or among those who seroconverted during the study, were not significantly different. When HSV-2 seroconversion was analyzed as a time-dependent covariate, the hazard ratio for HIV-1 seroconversion was 6.0 (95% CI: 2.6-14.0) times greater among women with incident than among women with prevalent HSV-2 infections. Drawing on other recent studies these data suggest that incident HSV-2 infection increases the risk of HIV-1 infection; the effect wanes with time since infection; and the effect is significantly greater for men than it is for women.

Adolescent↗

PubMed2005

Microbicide acceptability research: current approaches and future directions.

With growing recognition of the potential value of microbicides for HIV/STI prevention, the importance of the acceptability of this brand-new technology has been widely acknowledged. We review the current body of microbicide acceptability research, characterize the limitations in assessment approaches, and suggest strategies for improvement. Electronic databases and abstracts of recent meetings were searched for acceptability data regarding vaginal and rectal products that may be used for HIV prevention. Of the 61 studies reviewed, more than half assessed acceptability based primarily on the description of a hypothetical microbicide, or with the demonstration of a spermicide or lubricant. Physical characteristics of microbicidal products, their effects after insertion, and their effects on sensation during intercourse (for both partners) were the dimensions most frequently assessed (measured in 77%, 49% and 49% of studies, respectively). Attention to the social context of use was inadequate. As acceptability is likely to be a key determinant in the use-effectiveness of microbicides, in-depth understanding of the social processes that shape microbicide acceptability across diverse populations will become increasingly valuable. This includes exploring the effects that sexual partners, health care providers, and key opinion leaders have on the acceptability of microbicides among women and men, including youth and people living with HIV. Future research will benefit from studies of the acceptability of other contraceptive-barrier methods (especially the female condom), use of an agreed-upon operationalization of acceptability, use of acceptability assessments within clinical trials, expansion of measurement domains, and assessment of changes in perceptions of acceptability and use over time. Failure to understand the key factors associated with microbicide acceptability is likely to hinder the adoption and continued use of products that are effective in preventing HIV infection.

Anti-Infective Agents, Local↗

PubMed2004

Heterosexual transmission of multiple highly conserved viral variants in HIV-1 subtype C-infected seronegative women.

Viral population diversity was assessed in samples collected from five HIV-infected women who were RNA positive and antibody negative. Similar to studies in men, highly conserved viral variants were detected (mean nucleotide diversity of 0.11% for p17p24, 0.32% for C2C3). In two individuals diversity was uncharacteristically lower in env C2C3 than in gag pl7p24, suggesting selection in env at this very early stage of infection.

Clone Cells↗

PubMed2004

Incidence of HIV-1 dual infection and its association with increased viral load set point in a cohort of HIV-1 subtype C-infected female sex workers.

This longitudinal study aimed to determine the incidence and pathogenic implications of dual human immunodeficiency virus type 1 (HIV-1) infection in a cohort of female sex workers. Blood samples from 31 recently infected women were screened by use of a heteroduplex mobility assay and sequencing. The median viral load set point was 5404 copies/mL (n=22), which was measured by use of the bDNA assay. Within 3 months of infection, 19% (6/31) of the women were dually infected with 2 distinct HIV-1 subtype C viruses. No evidence of superinfection was detected over the course of 24 months of follow-up, indicating that the risk of dual infection is highest around the time of the initial infection. There was a significant association between dual infection and elevated viral load set point.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Characterization and selection of HIV-1 subtype C isolates for use in vaccine development.

HIV-1 genetic diversity among circulating strains presents a major challenge for HIV-1 vaccine development, particularly for developing countries where less sequence information is available. To identify representative viruses for inclusion in candidate vaccines targeted for South Africa, we applied an efficient sequence survey strategy to samples from recently and chronically infected persons residing in potential vaccine trial sites. All 111 sequences were subtype C, including 30 partial gag, 26 partial pol, 27 V2-V3 env, and 28 V5-partial gp41 sequences. Of the 10 viruses cultured from recently infected individuals, 9 were R5 and 1 was R5X4. Two isolates, Du151 and Du422, collected within 2 months of infection, were selected as vaccine strains on the basis of their amino acid similarity to a derived South African consensus sequence The selection of recently transmitted R5 isolates for vaccine design may provide an advantage in a subtype C R5-dominant epidemic. The full-length Du422 gag and Du151 pol and env genes were cloned into the Venezuelan equine encephalitis (VEE) replicon particle (VRP) expression system. Du422 Gag protein expressed from the VRP accumulated to a high level and was immunogenic as demonstrated by cytotoxic T lymphocyte responses in mice vaccinated with gag-VRPs. Optimization of codon use for VRP expression in human cells did not enhance expression of the gag gene. The cloned Du151 env gene encoded a functional protein as demonstrated by fusion of VRP-infected cells with cells expressing CD4 and CCR5. Genes identified in this study have been incorporated into the VEE VRP candidate vaccines targeted for clinical trial in South Africa.

AIDS Vaccines↗

PubMed2002

Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial.

BACKGROUND: Nonoxynol-9 (rINN, nonoxinol-9) is an over-the-counter spermicide that has in-vitro anti-HIV-1 activity. Results of studies of its effectiveness in prevention of HIV-1 infection in women have been inconclusive. We aimed to assess effectiveness of this vaginal gel. METHODS: We did a randomised, placebo-controlled, triple-blinded, phase 2/3 trial with COL-1492, a nonoxynol-9 vaginal gel, in 892 female sex workers in four countries: Benin, Côte d'Ivoire, South Africa, and Thailand. 449 women were randomly allocated nonoxynol-9 and 443 placebo. Primary endpoint was incident HIV-1 infection. Secondary endpoints included Neisseria gonorrhoeae and Chlamydia trachomatis infections. Analysis was by intention to treat. FINDINGS: 765 women were included in the primary analysis. HIV-1 frequency in nonoxynol-9 users was 59 (16%) of 376 compared with 45 (12%) [corrected] of 389 in placebo users (402.5 vs 435.0 woman-years; hazard ratio adjusted for centre 1.5; 95% CI 1.0-2.2; p=0.047). 239 (32%) women reported use of a mean of more than 3.5 applicators per working day, and in these women, risk of HIV-1 infection in nonoxynol-9 users was almost twice that in placebo users (hazard ratio 1.8; 95% CI 1.0-3.2). 516 (68%) women used the gel less frequently than 3.5 times a day, and in these, risk did not differ between the two treatments. No significant effect of nonoxynol-9 on N gonorrhoeae (1.2; 0.9-1.6) or C trachomatis (1.2; 0.8-1.6) infections was reported. INTERPRETATION: This study did not show a protective effect of COL-1492 on HIV-1 transmission in high-risk women. Multiple use of nonoxynol-9 could cause toxic effects enhancing HIV-1 infection. This drug can no longer be deemed a potential HIV-1-prevention method. Assessment of other microbicides should continue.

Adult↗

PubMed2002

Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomised controlled trials including more than 5000 women.

We aimed to determine the effectiveness of the vaginally administered spermicide nonoxynol-9 (N-9) among women for the prevention of HIV and other sexually transmitted infections (STIs). We did a systematic review of randomised controlled trials. Nine such trials including 5096 women, predominantly sex workers, comparing N-9 with placebo or no treatment, were included. Primary outcomes were new HIV infection, new episodes of various STIs, and genital lesions. Five trials included HIV and nine included STI outcomes, and all but one (2% of the data) contributed to the meta-analysis. Overall, relative risks of HIV infection (1.12, 95% confidence interval 0.88-1.42), gonorrhoea (0.91, 0.67-1.24), chlamydia (0.88, 0.77-1.01), cervical infection (1.01, 0.84-1.22), trichomoniasis (0.84, 0.69-1.02), bacterial vaginosis (0.88, 0.74-1.04) and candidiasis (0.97, 0.84-1.12) were not significantly different in the N-9 and placebo or no treatment groups. Genital lesions were more common in the N-9 group (1.18, 1.02-1.36). Our review has found no statistically significant reduction in risk of HIV and STIs, and the confidence intervals indicate that any protection that may exist is likely to be very small. There is some evidence of harm through genital lesions. N-9 cannot be recommended for HIV and STI prevention.

Adult↗

PubMed2002

Prevalence of HIV among truck drivers visiting sex workers in KwaZulu-Natal, South Africa.

BACKGROUND: Although the role of mobile populations in the spread of HIV has been documented in several countries, there are few data on HIV among truck drivers in South Africa and the sex workers with whom they interact. GOAL: To determine HIV prevalence and risk behavior in a sample of truck drivers visiting commercial sex workers at truck stops. STUDY DESIGN: Two sex workers from each of five truck stops were trained to obtain informed consent, administer questionnaires to obtain data on demographic and migration patterns, and collect saliva samples for HIV testing from their clients. Data on HIV prevalence and demographic characteristics of sex workers operating at the truck stops were obtained from an ongoing vaginal microbicide trial. RESULTS: The mean age of the truck drivers (all men) was 37 years (range, 18-71 years), and that of the sex workers (all females) was 25 years (range, 15-49 years). Sixty-six percent of the men reported having a sexually transmitted infection in the previous six months, and 37% always stopped for sex along the route. Twenty-nine percent reported never using condoms with sex workers, whereas 13% had used condoms with their wives. All men traveled to more than one province in South Africa, and 65% traveled to neighboring countries. Anal sex was practiced by 42% of the men. The overall HIV prevalence (in the two groups combined) was 56%. CONCLUSION: Truck drivers may have facilitated the spread of HIV infection throughout southern Africa.

Adolescent↗

PubMed2002

Incidence of Sexually Transmitted Infections among HIV-positive sex workers in KwaZulu-Natal, South Africa.

BACKGROUND: Improved treatment of sexually transmitted infections (STIs) is associated with decreased HIV incidence. However, the success of such programs among HIV-positive sex workers has not been shown. GOAL The goal of the study was to determine the incidence of STIs ( and infections) among HIV-positive sex workers. STUDY DESIGN: A cohort of HIV-positive sex workers was treated for all STIs at baseline and observed monthly to detect and treat new infections. RESULTS: Seventy-seven HIV-positive sex workers were followed up for a total of 58.1 women-years. The incidence rate per 100 women-years was 150 (CI: 120-180) infections; 66 (CI: 45-87) infections; 30 (CI: 14-42) infections; and 244 (CI: 200-280) STIs of any type. CONCLUSION: In this cohort of HIV-positive sex workers the incidence of STIs was high, despite their participation in a prevention program comprising monthly STI treatment, counseling, and condom promotion.

AIDS-Related Opportunistic Infections↗

PubMed2002

Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa.

Clade C is one of the most prevalent genetic subtypes of human immunodeficiency virus type 1 (HIV-1) in the world today and one of the least studied with respect to neutralizing antibodies. Most information on HIV-1 serology as it relates to neutralization is derived from clade B. Clade C primary isolates of HIV-1 from South Africa and Malawi were shown here to resemble clade B isolates in their resistance to inhibition by soluble CD4 and their sensitivity to neutralization by human monoclonal antibody immunoglobulin G1b12 and, to a lesser extent, 2F5. Unlike clade B isolates, however, all 16 clade C isolates examined resisted neutralization by 2G12. Infection with clade C HIV-1 in a cohort of female sex workers in South Africa generated antibodies that neutralized the autologous clade C isolate and T-cell-line-adapted (TCLA) strains of clade B. Neutralization of clade B TCLA strains was much more sensitive to the presence of autologous gp120 V3 loop peptides compared to the neutralization of clade C isolates in most cases. Thus, the native structure of gp120 on primary isolates of clade C will likely pose a challenge for neutralizing antibody induction by candidate HIV-1 vaccines much the same as it has for clade B. The autologous neutralizing antibody response following primary infection with clade C HIV-1 in South Africa matured slowly, requiring at least 4 to 5 months to become detectable. Once detectable, extensive cross-neutralization of heterologous clade C isolates from South Africa was observed, suggesting an unusual degree of shared neutralization determinants at a regional level. This high frequency of cross-neutralization differed significantly from the ability of South African clade C serum samples to neutralize clade B isolates but did not differ significantly from results of other combinations of clade B and C reagents tested in checkerboard assays. Notably, two clade C serum samples obtained after less than 2 years of infection neutralized a broad spectrum of clade B and C isolates. Other individual serum samples showed a significant clade preference in their neutralizing activity. Our results suggest that clades B and C are each comprised of multiple neutralization serotypes, some of which are more clade specific than others. The clustering of shared neutralization determinants on clade C primary HIV-1 isolates from South Africa suggests that neutralizing antibodies induced by vaccines will have less epitope diversity to overcome at a regional level.

Amino Acid Sequence↗