Browsing by Author "Mansoor, Leila Essop."

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Adherence challenges with drugs for pre-exposure prophylaxis to prevent HIV infection.
(Springer Verlag., 2013) Gengiah, Tanuja Narayansamy.; Moosa, Atika.; Naidoo, Anushka.; Mansoor, Leila Essop.
Background: There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy. Aim of the review: To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection. Methods: PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992–2013—all phase II and phase III safety and effectiveness studies—testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted. Results: Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence. Conclusion: Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important.
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.
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.
Cervicovaginal inflammation facilitates acquisition of less infectious HIV variants.
(Oxford University Press., 2017) Selhorst, Philippe.; Masson, Lindi.; Ismail, Sherazaan D.; Samsunder, Natasha.; Garrett, Nigel Joel.; Mansoor, Leila Essop.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Passmore, Jo-Ann Shelley.; Williamson, Carolyn.
Abstract available in pdf.
Disclosure of microbicide gel use to sexual partners: influence on adherence in the CAPRISA 004 trial.
(Springer., 2014) Mngadi, Kathryn Therese.; Maarschalk, Silvia.; Grobler, Anna Christina.; Mansoor, Leila Essop.; Fröhlich, Janet Ann.; Madlala, Bernadette T.; Ngcobo, Nelisiwe.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.
Abstract available in pdf.
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.
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.
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.
Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.
(Nature Publishing Group., 2018) McKinnon, Lyle R.; Liebenberg, Lenine Julie.; Yende-Zuma, Fortunate Nonhlanhla.; Archary, Derseree.; Ngcapu, Sinaye.; Sivro, Aida.; Nagelkerke, Nico.; Garcia Lerma, Gerardo.; Kashuba, Angela D. M.; Masson, Lindi.; Mansoor, Leila Essop.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Passmore, Jo-Ann Shelley.
Abstract available in pdf.
Genital—systemic chemokine gradients and the risk of HIV acquisition in women.
(Wolters Kluwer Health., 2017) Liebenberg, Lenine Julie.; Masson, Lindi.; Arnold, Kelly B.; McKinnon, Lyle R.; Werner, Lise.; Proctor, Elizabeth.; Archary, Derseree.; Mansoor, Leila Essop.; Lauffenburger, Douglas A.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Passmore, Jo-Ann Shelley.
Abstract available in pdf.
Impact of an adherence intervention on the effectiveness of tenofovir gel in the CAPRISA 004 trial.
(Springer., 2014) Mansoor, Leila Essop.; Abdool Karim, Quarraisha.; Werner, Lise.; Madlala, Bernadette T.; Ngcobo, Nelisiwe.; Cornman, Deborah H.; Amico, Kathy Rivet.; Fisher, Jeffrey D.; Fisher, William A.; MacQueen, Kathleen M.; Abdool Karim, Salim Safurdeen.
Abstract not available in pdf.
Influences of geo-spatial location on pre-exposure prophylaxis use in South Africa : positioning microbicides for better product uptake.
(Govender, E.M., Mansoor, L.E. and Abdool Karim, Q. 2017. Influences of geo-spatial location on pre-exposure prophylaxis use in South Africa: positioning microbicides for better product uptake. AIDS Care 29(6), 734-740., 2017) Abdool Karim, Quarraisha.; Govender, Eliza Melissa.; Mansoor, Leila Essop.
Abstract available in pdf.
Measurement of vaginal microbicide adherence using visual inspection as compared to ultra violet light assessment of returned empty gel applicators.
(2015) Upfold, Michele.; Mansoor, Leila Essop.
Introduction Finding a safe, effective and acceptable HIV prevention method is key to preventing new infections in women. Vaginal microbicide trials aim to do so, but adherence to study product remains a challenge in interpretation of study product effectiveness. Accurate and objective measures of adherence are critical in microbicide trials. Methods We compared two applicator tests, visual inspection of returned empty applicators (VIREA) and ultraviolet (UV) light assessment of empty applicators returned as used within a tenofovir (TFV) gel implementation trial. Sensitivity and specificity in a small pilot sample was assessed at two time points, approximately three months apart. Reliability and concordance of the techniques was also assessed. Results Sensitivity and specificity analysis of 24 sample applicators at time point 1 was 75.0% and 66.7% for VIREA and 83.3% and 91.7% for UV light assessment, respectively; Sensitivity and specificity at time point 2 was 100% and 58.3% for VIREA and 100% and 66.7% for UV light assessment, respectively. Participants (n=115, median age 28 years) enrolled in the implementation trial at the Vulindlela Research Clinic, returned 1316 empty TFV applicators as used in January 2015. Assessment outcomes showed 78.8% agreement between VIREA and UV light techniques. Methods concurred that 22% of the returned empty applicators did not appear to be used. UV light assessment identified about 28% less product used, as compared to that returned as used by women. Conclusion UV light assessment appears to be a more accurate and less subjective measure of adherence as compared to VIREA. Further studies are needed to verify accuracy of UV light inspection against available DNA/protein biomarkers. UV light assessment can be used in combination with other biomarkers to identify potential challenges to adherence and inform targeted adherence interventions with the intention of optimizing adherence during microbicide clinical trials.
Measuring adherence by visual inspection of returned empty gel applicators in the CAPRISA 004 microbicide trial.
(Springer., 2014) Gengiah, Tanuja Narayansamy.; Mansoor, Leila Essop.; Upfold, Michele.; Naidoo, Anushka.; Yende-Zuma, Fortunate Nonhlanhla.; Kashuba, Angela D. M.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.
Abstract not available in pdf.
Microbicide clinical trial adherence: insights for introduction.
(BioMed Central., 2012) Woodsong, Cynthia.; MacQueen, Kathleen M.; Amico, Kathy Rivet.; Friedland, Barbara A.; Gafos, Mitzy.; Mansoor, Leila Essop.; Tolley, Elizabeth E.; McCormack, Sheena.
After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants’ adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.
Monitoring microbicide gel use with real-time notification of the container’s opening events : results of the CAPRISA Wisebag study.
(Springer., 2014) Gengiah, Tanuja Narayansamy.; Upfold, Michele.; Naidoo, Anushka.; Mansoor, Leila Essop.; Feldblum, Paul J.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.
Accurate estimation of the effectiveness of a microbicide for HIV prevention requires valid measurement of adherence to product use. A microbicide gel applicator container (Wisebag), fitted with cell phone technology to transmit opening events and text message reminders, was developed to monitor each opening event of the container as a proxy for gel use and adherence. Ten women were enrolled in a pilot study and followed for up to 4 months. Wisebag opening (WBO) dates and times were recorded and correlated with self-reported sex acts and gel applicator returns. During the 33 monthly follow-up visits, 47.8% (77/161) of the recorded number of WBO events were concordant with the number of empty (used) applicators returned. The discrepancies were likely due to removal of more than one applicator during a single opening event. When the date and time of the WBO event data was assessed in relation to three different self-report adherence measures, agreement was fairly modest. The Wisebag was found to be acceptable as a storage container and the cell phone reminders generated were useful in supporting the dosing strategy. We recommend that the Wisebag be considered for larger scale and lengthier testing in microbicide trials.
Narratives from women using the dapivirine vaginal ring in an open label extension study by Kalendri Naidoo.
(2022) Naidoo, Kalendri.; Mansoor, Leila Essop.; Montgomery, Elizabeth T.
In sub-Saharan Africa, women and girls represented 63% of new Human Immunodeficiency Virus (HIV) infections in 2020. Adolescent girls and young women (AGYW) aged 15–24 years are twice as likely to be living with HIV as compared to young men. Therefore, efforts to develop and roll out safe, effective and acceptable HIV prevention products for women, are continuing. An important example of a female-initiated HIV prevention strategy is the dapivirine vaginal ring which showed a 27% reduction in HIV-1 incidence in the Microbicides Trials Network (MTN)-020/A Study to Prevent Infection with a Ring for Extended Use (ASPIRE) study and by 31% in the International Partnership for Microbicides (IPM)-027 The Ring study. The dapivirine vaginal ring was subsequently tested for safety and adherence in the Open Label Extension (OLE), MTN-025/HIV Open-label Prevention Extension (HOPE) study. The MTN-032/Adherence in HOPE and ASPIRE (AHA) study was a two-phase exploratory sub-study of the ASPIRE (AHA part 1, after ASPIRE and before HOPE study initiation) and HOPE (AHA part 2, after HOPE was completed) studies which utilised single qualitative indepth interviews (IDIs) to explore social conditions and issues related to participation around the use of the dapivirine vaginal ring as well as suitable approaches to market the study product. I report on the narratives from women participating in the AHA study (Part 2) within the context of known safety, partial product efficacy and choice, focusing on what motivated women to join the HOPE OLE study, women’s understanding of the vaginal rings’ efficacy, how they understood it to work in their bodies to prevent HIV and barriers and motivators to vaginal ring adherence.
The preventive misconception: experiences from CAPRISA 004.
(Springer., 2014) Dellar, Rachael Claire.; Abdool Karim, Quarraisha.; Mansoor, Leila Essop.; Grobler, Anna Christina.; Humphries, Hilton Richard.; Werner, Lise.; Ntombela, Fanelesibonge.; Luthuli, Londiwe R.; Abdool Karim, Salim Safurdeen.
Abstract available in pdf.
Recruitment of high risk women for HIV prevention trials: baseline HIV prevalence and sexual behavior in the CAPRISA 004 tenofovir gel trial.
(Biomed Central, 2010) Abdool Karim, Quarraisha.; Kharsany, Ayesha Bibi Mahomed.; Fröhlich, Janet Ann.; Baxter, Cheryl.; Yende Zuma, Nonhlanhla.; Mansoor, Leila Essop.; Mlisana, Koleka Patience.; Maarschalk, Silvia.; Arulappan, Natasha.; Grobler, Anna Christina.; Sibeko, Sengeziwe.; Omar, Zaheen.; Gengiah, Tanuja Narayansamy.; Mlotshwa, Mukelisiwe.; Samsunder, Natasha.; Abdool Karim, Salim Safurdeen.
Background: Young women in sub-Saharan Africa bear a disproportionate burden of HIV infection compared to men but have limited options to reduce their HIV risk. Microbicides could fill an important HIV prevention gap for sexually active women who are unable to successfully negotiate mutual monogamy or condom use. Purpose: This paper describes the baseline sample characteristics in the CAPRISA 004 trial which assessed the safety and effectiveness of the vaginal microbicide, 1% tenofovir gel for HIV prevention in South Africa. Methods: This analysis assessed the baseline demographic, clinical and sexual behavior data of women screened and enrolled into the trial. The characteristics were summarized using descriptive summary measures; expressed as means and percent for categorical variables. Results: HIV prevalence at screening was 25.8% [95% Confidence Interval (CI):23.9-27.7). Of the 889 eligibly enrolled women who contributed follow-up data, rural participants recruited from a family planning (FP) clinic were younger, more likely to be living apart from their regular partner, reported lower coital frequency, had lower condom use (p < 0.001). In contrast, urban participants recruited from a sexually transmitted disease (STD) clinic reported higher numbers of lifetime sexual partners, new partners in the last 30 days and receiving money in exchange for sex (p < 0.001). Conclusion: The populations selected provide suitable diverse target groups for HIV prevention intervention studies.
Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.
(International Medical Press., 2012) Sokal, David C.; Abdool Karim, Quarraisha.; Sibeko, Sengeziwe.; Yende Zuma, Nonhlanhla.; Mansoor, Leila Essop.; Baxter, Cheryl.; Grobler, Anna Christina.; Fröhlich, Janet Ann.; Kharsany, Ayesha Bibi Mahomed.; Miya, Nomsa.; Mlisana, Koleka Patience.; Maarschalk, Silvia.; Abdool Karim, Salim Safurdeen.
Background: Tenofovir gel, used vaginally before and after coitus, reduced women’s acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters. Methods: In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated. Results: Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group. Conclusions: No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile.