Research papers (Caprisa)

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The abandoned trials of pre-exposure prophylaxis for HIV : what went wrong?
(Plos., 2005) Singh, Jerome Amir.; Mills, Edward J.
Discusses the impact of irresponsible reporting and activism against the use of the oral antiretroviral drug tenofovir as a pre-exposure prophylaxis (PREP) for HIV/AIDS. Protests against trials of PREP; Concerns of the protestors; Threats to PREP trials.
Ability to develop broadly neutralizing HIV-1 antibodies is not restricted by the germline Ig gene repertoire.
(American Association of Immunologists., 2015) Scheepers, Cathrine.; Shrestha, Ram K.; Lambson, Bronwen Elizabeth.; Jackson, Katherine J. L.; Wright, Imogen A.; Naicker, Dshanta Dyanedi.; Goosen, Mark.; Berrie, Leigh.; Ismail, Arshad.; Garrett, Nigel Joel.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Moore, Penelope L.; Travers, Simon A.; Morris, Lynn.
Abstract available in pdf.
Acceptability of early antiretroviral therapy among South African women.
(Springer., 2018) Garrett, Nigel Joel.; Norman, Emily.; Leask, Kerry.; Naicker, Nivashnee.; Asari, Villeshni.; Majola, Nelisile.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.
Abstract available in pdf.
Acceptability of HIV self-testing in sub-Saharan Africa: scoping study.
(Springer., 2018) Harichund, Charlene.; Moshabela, Matlagolo Mosa.
Abstract available in pdf.
Achieving the health Millennium Development Goals for South Africa : challenges and priorities.
(Elsevier., 2009) Chopra, Mickey.; Lawn, Joy E.; Sanders, David.; Barron, Peter.; Abdool Karim, Salim Safurdeen.; Bradshaw, Debbie.; Jewkes, Rachel.; Abdool Karim, Quarraisha.; Flisher, Alan J.; Mayosi, Bongani M.; Tollman, Stephen M.; Churchyard, Gavin J.; Coovadia, Hoosen Mahomed.
15 years after liberation from apartheid, South Africans are facing new challenges for which the highest calibre of leadership, vision, and commitment is needed. The effect of the unprecedented HIV/AIDS epidemic has been immense. Substantial increases in mortality and morbidity are threatening to overwhelm the health system and undermine the potential of South Africa to attain the Millennium Development Goals (MDGs). However The Lancet’s Series on South Africa has identified several examples of leadership and innovation that point towards a different future scenario. We discuss the type of vision, leadership, and priority actions needed to achieve such a change. We still have time to change the health trajectory of the country, and even meet the MDGs. The South African Government, installed in April, 2009, has the mandate and potential to address the public health emergencies facing the country—will they do so or will another opportunity and many more lives be lost?
Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure.
(Elsevier., 2009) Treurnicht, Florette K.; Seoighe, Cathal.; Martin, Darren Patrick.; Wood, N.; Abrahams, Melissa-Rose.; de Assis Rosa, Debra.; Bredell, Helba.; Woodman, Zenda.; Hide, Winston.; Mlisana, Koleka Patience.; Abdool Karim, Salim Safurdeen.; Gray, Clive M.; Williamson, Carolyn.
It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential “transmission signatures”, we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission.
An adaptive design to bridge the gap between phase 2b/3 microbicide effectiveness trials and evidence required for licensure.
(Sage., 2012) Taylor, Douglas.; Grobler, Anna Christina.; Abdool Karim, Salim Safurdeen.
Background. Vaginally and rectally applied microbicides are being developed to help prevent sexual acquisition of HIV. Due to the lack of surrogate outcomes, the path toward licensure typically moves directly from expanded safety studies to expensive Phase 2b/3 trials with rare incident infection outcomes. The need to confirm an initial trial’s significant finding can lead to serious delays in implementing essential programs to reduce the spread of HIV. Purpose. To propose an adaptive design where a Phase 2b/3 study powered to detect a clinically meaningful effect with evidence of one trial (observing one-sided p < 0.025) is allowed to expand by a prespecified, feasible amount if interim data suggest the chance of further achieving a more robust evidence threshold ( p < 0.001, potentially sufficient for licensure from a single trial) is promising. Methods. As an example, prespecified conditional power criteria are used to determine whether a 90-event trial with 90% power to detect a 50% reduction in risk should be expanded to 130 events. Asymptotic results and simulations are used to assess false-positive error rates and other operating characteristics of the design. Results. False-positive error rates can be controlled at the desired 0.025 and 0.001 levels with appropriate choice of critical values or expansion criteria. The chance of achieving robust evidence can approach that of a 130-event trial with traditional stopping boundaries (controlling a = 0.001) but with substantially lower expected size for plausible effectiveness levels. Limitations. Conditional power calculations assume the interim estimate of effect is an unbiased estimate for the remainder of the trial, an assumption which may not hold if product adherence varies over time. Observing a measure of effect with p < 0.001 may not be sufficient for licensure. A decision to expand the trial would be informative to investigators regarding the interim effect size. Conclusions. A moderate increase in trial size can make the difference between a study with good power to detect a clinically meaningful effect and one which may reasonably obtain the robust evidence required for regulatory bodies and public health programs to consider making a new microbicide available to persons at risk of HIV infection. The proposed design allows for this possibility while not requiring investigators to make an up-front commitment to a prohibitively large trial.
Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol.
(Implementation Science., 2015) Naidoo, Kogieleum.; Gengiah, Santhanalakshmi.; Yende-Zuma, Fortunate Nonhlanhla.; Padayatchi, Nesri.; Barker, Pierre.; Nunn, Andrew.; Subrayen, Priashni.; Abdool Karim, Salim Safurdeen.
Abstract available in pdf.
Addressing ethical, social, and cultural issues in global health research.
(Plos., 2013) Lavery, James V.; Green, Shane K.; Bandewar, Sunita V. S.; Bhan, Anant.; Daar, Abdallah S.; Emerson, Claudia I.; Masum, Hassan.; Randazzo, Filippo M.; Singh, Jerome Amir.; Upshur, Ross Edward Grant.; Singer, Peter A.
The purpose of this paper is to encourage reflection among the global health research community and the research ethics community about how a wide range of ethical, social, and cultural (ESC) influences on the conduct, success, and impact of global health research can best be addressed by consultation services in research ethics (CSRE). We draw on lessons we have learned during our experiences with the ESC Program of the Grand Challenges in Global Health initiative to propose key features of CSRE that may prove useful for those designing or implementing similar programs.
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.
Adherence in the treatment of patients with extensively drug-resistant tuberculosis and HIV in South Africa: a prospective cohort study.
(Lippincott Williams & Wilkins., 2014) O'Donnell, Max Roe.; Wolf, Allison.; Werner, Lise.; Horsburgh, Charles Robert.; Padayatchi, Nesri.
Abstract available in pdf.
Adjusting the effect of integrating antiretroviral therapy and tuberculosis treatment on mortality for non-compliance: a time-varying instrumental variables analysis.
(Wolters Kluwer., 2019) Mwambi, Henry.; Vansteelandt, Stijn.; Yende-Zuma, Fortunate Nonhlanhla.
Abstract available in PDF.
Adolescent antiretroviral management: Understanding the complexity of non-adherence.
(South African Medical Association., 2015) Naidoo, Kala N.; Munsami, Adele.; Archary, Moherndran.
Abstract available in pdf.
Adolescent girls and young women: key populations for HIV epidemic control.
(International AIDS Society., 2015) Dellar, Rachael Claire.; Dlamini, Sarah Alexandra.; Abdool Karim, Quarraisha.
Abstract available in pdf.
Adolescent HIV treatment issues in South Africa.
(South African Medical Association., 2015) Dawood, Halima.
Abstract available in pdf.
Adolescents and HIV clinical trials: ethics, culture, and context.
(Elsevier., 2007) MacQueen, Kathleen M.; Abdool Karim, Quarraisha.
One quarter of HIV infections globally occur among young people 15-24 years of age and more than half of all new infections are to people younger than 25 years. Clearly, there is a need to identify and implement effective HIV prevention strategies among at-risk teens. Some of the most effective options for slowing the epidemic are biomedical and several promising methods are in development, including microbicides, vaccines, and pre-exposure prophylaxis (PREP) or the daily use of antiretrovirals to prevent the acquisition of HIV. There is widespread reluctance to enroll minors in such biomedical prevention trials due to concerns about vulnerability related to physical maturity, experiential maturity, and diminished autonomy as well as legal and social challenges that vary across and within nations. However, excluding minors from trials misses an important opportunity to evaluate the effectiveness, acceptability, and safety of innovative interventions under the best conditions for identifying and resolving potential problems. The challenges of including minors in HIV prevention trials are highlighted via the example of one rural South African community that has been particularly devastated by the HIV epidemic.
Advances in childhood immunisation in South Africa: where to now? Programme managers’ views and evidence from systematic reviews.
(BioMed Central., 2012) Wiysonge, Charles Shey.; Ngcobo, Nthombenhle J.; Jeena, Prakash M.; Madhi, Shabir A.; Schoub, Barry D.; Hawkridge, Anthony.; Shey, Muki Shehu.; Hussey, Gregory D.
Background: The Expanded Programme on Immunisation (EPI) is one of the most powerful and cost-effective public health programmes to improve child survival. We assessed challenges and enablers for the programme in South Africa, as we approach the 2015 deadline for the Millennium Development Goals. Methods: Between September 2009 and September 2010 we requested national and provincial EPI managers in South Africa to identify key challenges facing EPI, and to propose appropriate solutions. We collated their responses and searched for systematic reviews on the effectiveness of the proposed solutions; in the Health Systems Evidence, Cochrane Library, and PubMed electronic databases. We screened the search outputs, selected systematic reviews, extracted data, and assessed the quality of included reviews (using AMSTAR) and the quality of the evidence (using GRADE) in duplicate; resolving disagreements by discussion and consensus. Results: Challenges identified by EPI managers were linked to healthcare workers (insufficient knowledge of vaccines and immunisation), the public (anti-immunisation rumours and reluctance from parents), and health system (insufficient financial and human resources). Strategies proposed by managers to overcome the challenges include training, supervision, and audit and feedback; strengthening advocacy and social mobilisation; and sustainable EPI funding schemes, respectively. The findings from reliable systematic reviews indicate that interactive educational meetings, audit and feedback, and supportive supervision improve healthcare worker performance. Structured and interactive communication tools probably increase parents’ understanding of immunisation; and reminders and recall, use of community health workers, conditional cash transfers, and mass media interventions probably increase immunisation coverage. Finally, a national social health insurance scheme is a potential EPI financing mechanism; however, given the absence of high-quality evidence of effects, its implementation should be pilot-tested and the impacts and costs rigorously monitored. Conclusion: In line with the Millennium Development Goals, we have to ensure that our children’s right to health, development and survival is respected, protected and promoted. EPI is central to this vision. We found numerous promising strategies for improving EPI performance in South Africa. However, their implementation would need to be tailored to local circumstances and accompanied by high-quality monitoring and evaluation. The strength of our approach comes from having a strong framework for interventions before looking for systematic reviews. Without a framework, we would have been driven by what reviews have been done and what is easily researchable; rather than the values and preferences of key immunisation stakeholders.
Advancing STI care in low/middle-income countries : has STI syndromic management reached its use-by date?
(‎BMJ Group., 2017) Garrett, Nigel Joel.; McGrath, Nuala.; Mindel, Adrian.
Abstract available in pdf.
Aetiology, clinical presentation, and outcome of meningitis in patients coinfected with human immunodeficiency virus and tuberculosis.
(Hindawi Publishing Corporation., 2011) Bhagwan, Smita.; Naidoo, Kogieleum.
We conducted a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients.Mortality was 70% (7/10), with 4 deaths directly due to meningitis. In an HIV TB endemic region we identified cryptococcus followed by tuberculosis as the leading causes of meningitis. We highlight the occurrence of tuberculous meningitis in patients already receiving antituberculous therapy. The development of meningitis heralded poor outcomes, high mortality, and relapsing meningitis despite ART.

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