Browsing by Author "Baxter, Cheryl."

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Adherence in the CAPRISA 004 tenofovir gel microbicide trial.
(Springer., 2014) Mansoor, Leila Essop.; Abdool Karim, Quarraisha.; Yende-Zuma, Fortunate Nonhlanhla.; MacQueen, Kathleen M.; Baxter, Cheryl.; Madlala, Bernadette T.; Grobler, Anneke.; Abdool Karim, Salim Safurdeen.
High adherence is key to microbicide effectiveness. Here we provide a description of adherence interventions and the adherence rates achieved in the CAPRISA 004 Tenofovir Gel Trial. Adherence support for the before-and-after dosing strategy (BAT 24) was provided at enrolment and at each monthly study visit. This initially comprised individual counselling and was replaced midway by a structured theory-based adherence support program (ASP) based on motivational interviewing. The 889 women were followed for an average of 18 months and attended a total of 17031 monthly visits. On average women reported 5 sex acts and returned 5.9 empty applicators per month. The adherence rate based on applicator count in relation to all reported sex acts was 72.2% compared to the 82.0% self-reported adherence during the last sex act. Adherence support activities, which achieve levels of adherence similar to or better than those achieved by the CAPRISA 004 ASP, will be critical to the success of future microbicide trials.
Antibodies for HIV prevention in young women.
(Wolters Kluwer., 2015) Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Baxter, Cheryl.
Abstract available.
Antiretroviral therapy : challenges and options in South Africa.
(Elsevier., 2003) Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Baxter, Cheryl.
No abstract available.
Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: study protocol for an open-label randomized controlled trial.
(BioMed Central., 2014) Mansoor, Leila Essop.; Abdool Karim, Quarraisha.; Mngadi, Kathryn Therese.; Dlamini, Sarah Alexandra.; Montague, Carl.; Nkomonde, Nelisiwe.; Mvandaba, Nomzamo.; Baxter, Cheryl.; Gengiah, Tanuja Narayansamy.; Samsunder, Natasha.; Dawood, Halima.; Grobler, Anna Christina.; Fröhlich, Janet Ann.; Abdool Karim, Salim Safurdeen.
Background: The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide post-trial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial. Methods/design: This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision. Discussion: This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scale-up of microbicides within the public health system of South Africa. Trial registration: This trial was registered with the South Africa Department of Health (reference: DOH-27-0812-4129) and ClinicalTrials.gov (reference: NCT01691768) on 05 July 2012.
Combination HIV prevention options for young women in Africa.
(National Inquiry Services Centre., 2016) Baxter, Cheryl.; Abdool Karim, Salim Safurdeen.
Abstract available in PDF file.
Contraceptive choices, pregnancy rates, and outcomes in a microbicide trial.
(Lippincott Williams & Wilkins., 2011) Sibeko, Sengeziwe.; Baxter, Cheryl.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Yende Zuma, Nonhlanhla.
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.
A drug evaluation of 1% tenofovir gel and tenofovir disoproxil fumarate tablets for the prevention of HIV infection.
(Informa Healthcare., 2011) Gengiah, Tanuja Narayansamy.; Baxter, Cheryl.; Mansoor, Leila Essop.; Kharsany, Ayesha Bibi Mahomed.; Abdool Karim, Salim Safurdeen.
Introduction: More than a million people acquire HIV infection annually. Pre-exposure prophylaxis (PrEP) using antiretrovirals is currently being investigated for HIV prevention. Oral and topical formulations of tenofovir have undergone preclinical and clinical testing to assess acceptability, safety and effectiveness in preventing HIV infection. Areas covered: The tenofovir drug development pathway from compound discovery, preclinical animal model testing and human testing were reviewed for safety, tolerability and efficacy. Tenofovir is well tolerated and safe when used both systemically or applied topically for HIV prevention. High drug concentrations at the site of HIV transmission and concomitant low systemic drug concentrations are achieved with vaginal application. Coitally applied gel may be the favored prevention option for women compared with the tablets, which may be more suitable for prevention in men and sero-discordant couples. However, recent contradictory effectiveness outcomes in women need to be better understood. Expert opinion: Emerging evidence has brought new hope that antiretrovirals can potentially change the course of the HIV epidemic when used as early treatment for prevention, as topical or oral PrEP. Although some trial results appear conflicting, behavioral factors, adherence to dosing and pharmacokinetic properties of the different tenofovir formulations and dosing approaches offer plausible explanations for most of the variations in effectiveness observed in different trials.
The effect of genital tract inflammation on HIV-specific binding antibodies, IgG subclass and Isotype transudation.
(2019) Pillay, Thevani.; Archary, Derseree.; Baxter, Cheryl.
Abstract available in PDF file.
Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women.
(American Association for the Advancement of Science., 2010) Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Fröhlich, Janet Ann.; Grobler, Anna Christina.; Baxter, Cheryl.; Mansoor, Leila Essop.; Kharsany, Ayesha Bibi Mahomed.; Sibeko, Sengeziwe.; Mlisana, Koleka Patience.; Omar, Zaheen.; Gengiah, Tanuja Narayansamy.; Maarschalk, Silvia.; Arulappan, Natasha.; Mlotshwa, Mukelisiwe.; Morris, Lynn.; Taylor, Douglas.
The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.
Functional assessment on non-neutralizing binding antibodies in the blood and genital tracts of women with breakthrough HIV infection from the CAPRISA 004 1% tenofovir gel trial.
(2017) Fisher, Kimone Leigh.; Archary, Derseree.; Baxter, Cheryl.
Abstract available in PDF file.
Genital inflammation and the risk of HIV acquisition in women.
(Oxford University Press., 2015) Masson, Lindi.; Passmore, Jo-Ann Shelley.; Liebenberg, Lenine Julie.; Werner, Lise.; Baxter, Cheryl.; Arnold, Kelly B.; Williamson, Carolyn.; Little, Francesca.; Mansoor, Leila Essop.; Naranbhai, Vivek.; Lauffenburger, Douglas A.; Ronacher, Katharina.; Walzl, Gerhard.; Garrett, Nigel Joel.; Williams, Brent L.; Couto-Rodriguez, Mara.; Hornig, Mady.; Lipkin, Walter Ian.; Grobler, Anna Christina.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.
Abstract available in pdf.
Global epidemiology of HIV-AIDS.
(WB Saunders., 2007) Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Gouws, Eleanor.; Baxter, Cheryl.
HIV, the cause of AIDS, has in the 25 years since its discovery spread rapidly to every region in the world [1]. To date, more than 65 million people have been infected with HIV and about 25 million people have died from AIDS [1]. In the current decade of the epidemic, there has been a substantial increase in HIV infection in women, and about 40% of all new infections among adults occurred in young people 15 to 24 years of age. At the end of 2006 [2], the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that there were a total of 39.5 million (34.1–47.1 million) adults and children living with HIV. In 2006, a total of 4.3 million (3.6–6.6 million) new infections occurred and 2.9 million (2.5–3.5 million) people died from AIDS.
HIV vaccines and immunity.
(Allergy Society of South Africa., 2003) Abdool Karim, Salim Safurdeen.; Baxter, Cheryl.
No abstract available.
The impact of semen exposure on cytokine response and bacterial vaginosis in the female genital tract.
(2018) Mngomezulu, Khanyisile Happiness.; Ngcapu, Sinaye.; Baxter, Cheryl.
Background: Diverse microbial communities and inflammatory cytokine responses in the lower female genital tract (FGT) are closely associated with increased human immunodeficiency virus (HIV-1) risk, possibly through increasing mucosal HIV target cell frequency and T-cell activation. The presence of semen in the vagina during unprotected sex has been associated with short-term activation of mucosal immunity. Here, we investigated the extent to which partner semen impacts on cytokine and microbial profiles measured in 248 HIV-uninfected women at high risk for HIV infection. Methods: We assessed the semen exposure in SoftCup supernatants by quantifying prostate specific antigen (PSA) levels using enzyme-linked immunosorbent assay (ELISA). Luminex was used to measure 48 cytokines in SoftCup supernatants and the vaginal swabs were used for diagnosis of bacterial vaginosis by Nugent score. Results: PSA, which denotes semen exposure within 48 hours prior to sampling, was detected in 19% (43/248) of SoftCup supernatants. Of the 43 PSA positive women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had non-Lactobacillus dominant microbiota (Nugent score >7). In addition, PSA was significantly associated with prevalent bacterial vaginosis (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029), after adjusting for potential confounders such as age, STIs, current contraceptive use and condom use. Furthermore, women with detectable PSA had high median concentrations of Macrophage inflammatory protein- beta (MIP-1β) (p=0.047) compared to those without PSA. Conclusion: These findings suggest that the presence of semen has a potential to alter the inflammatory response and microbial communities of the FGT, which may facilitate recruitment of HIV susceptible cells, resulting in increased susceptibility to HIV-1 infection.
The impact of semen exposure on cytokine response and bacterial vaginosis in the female genital tract.
(2018) Mngomezulu, Khanyisile Happiness.; Ngcapu, Sinaye.; Baxter, Cheryl.
Background: Diverse microbial communities and inflammatory cytokine responses in the lower female genital tract (FGT) are closely associated with increased human immunodeficiency virus (HIV-1) risk, possibly through increasing mucosal HIV target cell frequency and T-cell activation. The presence of semen in the vagina during unprotected sex has been associated with short-term activation of mucosal immunity. Here, we investigated the extent to which partner semen impacts on cytokine and microbial profiles measured in 248 HIV-uninfected women at high risk for HIV infection. Methods: We assessed the semen exposure in SoftCup supernatants by quantifying prostate specific antigen (PSA) levels using enzyme-linked immunosorbent assay (ELISA). Luminex was used to measure 48 cytokines in SoftCup supernatants and the vaginal swabs were used for diagnosis of bacterial vaginosis by Nugent score. Results: PSA, which denotes semen exposure within 48 hours prior to sampling, was detected in 19% (43/248) of SoftCup supernatants. Of the 43 PSA positive women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had non-Lactobacillus dominant microbiota (Nugent score >7). In addition, PSA was significantly associated with prevalent bacterial vaginosis (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029), after adjusting for potential confounders such as age, STIs, current contraceptive use and condom use. Furthermore, women with detectable PSA had high median concentrations of Macrophage inflammatory protein- beta (MIP-1β) (p=0.047) compared to those without PSA. Conclusion: These findings suggest that the presence of semen has a potential to alter the inflammatory response and microbial communities of the FGT, which may facilitate recruitment of HIV susceptible cells, resulting in increased susceptibility to HIV-1 infection.
Improving adolescent maternal health.
(South African Medical Association., 2015) Baxter, Cheryl.; Moodley, Dhayendre.
Abstract available in pdf.
Integration of antiretroviral therapy with tuberculosis treatment.
(Massachusetts Medical Society., 2011) Abdool Karim, Salim Safurdeen.; Naidoo, Kogieleum.; Grobler, Anna Christina.; Padayatchi, Nesri.; Baxter, Cheryl.; Gray, Andrew Lofts.; Gengiah, Tanuja Narayansamy.; Gengiah, Santhanalakshmi.; Naidoo, Anushka.; Jithoo, Niraksha.; Nair, Gonasagrie.; El-Sadr, Wafaa M.; Friedland, Gerald H.; Abdool Karim, Quarraisha.
Background. We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved. Methods. We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier- ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here. Results. At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P = 0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P = 0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P = 0.006). Conclusions. Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death.
Microbicides & their implications in HIV prevention.
(MedKnow Publications., 2010) Abdool Karim, Salim Safurdeen.; Baxter, Cheryl.
No abstract available.
Microbicides and their potential as a catalyst for multipurpose sexual and reproductive health technologies.
(Wiley Online Library., 2014) Abdool Karim, Quarraisha.; Baxter, Cheryl.; Abdool Karim, Salim Safurdeen.
Abstract available in pdf.
The need for multipurpose prevention technologies in sub-Saharan Africa.
(Wiley Online Library., 2014) Abdool Karim, Salim Safurdeen.; Baxter, Cheryl.; Fröhlich, Janet Ann.; Abdool Karim, Quarraisha.
Abstract available in pdf.