Browsing by Author "Yende-Zuma, Fortunate Nonhlanhla."

Now showing 1 - 20 of 25

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.
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.
Adjusting the effect of integrating antiretroviral therapy and tuberculosis treatment on mortality for non-compliance : an instrumental variables analysis using a time-varying exposure.
(2018) Yende-Zuma, Fortunate Nonhlanhla.; Mwambi, Henry Godwell.; Vansteelandt, Stijn.
In South Africa and elsewhere, research has shown that the integration of antiretroviral therapy (ART) and tuberculosis (TB) treatment saves lives. The randomised controlled trials (RCTs) which provided this compelling evidence used intent-to-treat (ITT) strategy as part of their primary analysis. As much as ITT is protected against selection bias caused by both measured and unmeasured confounders, but it is capable of drawing results towards the null and underestimate the e ectiveness of treatment if there is too much non-compliance. To adjust for non-compliance, \as-treated"and \per-protocol"comparisons are commonly made. These contrast study participants according to their received treatment, regardless of the treatment arm to which they were assigned, or limit the analysis to participants who followed the protocol. Such analyses are generally biased because the subgroups which they compare often lack comparability. In view of the shortcomings of the \as-treated"and \per-protocol"analyses, our objective was to account for non-compliance by using instrumental variables (IV) analysis to estimate the e ect of ART initiation during TB treatment on mortality. Furthermore, to capture the full complexity of compliance behaviour outside the TB treatment duration, we developed a novel IV-methodology for a time-varying measure of compliance to ART. This is an important contribution to the IV literature since IV-methodology for the e ect of a time-varying exposure on a time-to-event endpoint is currently lacking. In RCTs, IV analysis enable us to make use of the comparability o ered by randomisation and thereby have the capability of adjusting for unmeasured and measured confounders; they have the further advantage of yielding results that are less sensitive to random measurement error in the exposure. In order to carry out IV analysis, one needs to identify a variable called an instrument, which needs to satisfy three important assumptions. To apply the IV methodology, we used data from Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) trial which was conducted by the Centre for the AIDS Programme of Research in South Africa. This trial enrolled HIV and TB co-infected patients who were assigned to start ART either early or late during TB treatment or after TB treatment completion. The results from IV analysis demonstrate that survival bene t of fully integrating TB treatment and ART is even higher than what has been reported in the ITT analysis since non-compliance has been accounted for.
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.
Assessing adherence to antiretroviral therapy in a rural paediatric cohort in KwaZulu-Natal, South Africa.
(Springer., 2016) Smith, Chanelle.; Gengiah, Tanuja Narayansamy.; Yende-Zuma, Fortunate Nonhlanhla.; Upfold, Michele.; Naidoo, Kogieleum.
Abstract available in pdf.
Case report: mechanisms of HIV elite control in two African women.
(BioMed Central., 2018) Moosa, Yumna.; Tanko, Ramla F.; Ramsuran, Veron.; Singh, Ravesh.; Madzivhandila, Mashudu.; Yende-Zuma, Fortunate Nonhlanhla.; Abrahams, Melissa-Rose.; Selhorst, Philippe.; Gounder, Kamini.; Moore, Penelope L.; Williamson, Carolyn.; Abdool Karim, Salim Safurdeen.; Garrett, Nigel Joel.; Burgers, Wendy A.
Abstract available in pdf.
CD8+ T cell breadth and ex vivo virus inhibition capacity distinguish between viremic controllers with and without protective HLA class I alleles.
(American Society for Microbiology., 2016) Koofhethile, Catherine Kegakilwe.; Ndhlovu, Zaza Mtine.; Thobakgale, Christina Fanesa.; Prado, Julia G.; Ismail, Nasreen.; Mncube, Zenele.; Mkhize, Lungile.; Van der Stok, Mary Elizabeth.; Yende-Zuma, Fortunate Nonhlanhla.; Walker, Bruce D.; Goulder, Philip Jeremy Renshaw.; Ndung'u, Peter Thumbi.
Abstract available in PDF file.
Changes to antiretroviral drug regimens during integrated TB-HIV treatment: results of the SAPiT trial.
(International Medical Press., 2014) Naidoo, Anushka.; Naidoo, Kogieleum.; Yende-Zuma, Fortunate Nonhlanhla.; Gengiah, Tanuja Narayansamy.; Padayatchi, Nesri.; Gray, Andrew Lofts.; Bamber, Sheila.; Nair, Gonasagrie.; Abdool Karim, Salim Safurdeen.
Background—Frequency of drug changes in combination antiretroviral therapy among patients starting both tuberculosis (TB) and human immunodeficiency virus (HIV) therapy, as a result of treatment-limiting toxicity or virological failure, is not well established. Methods—Patients in the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) trial were randomized to initiate antiretroviral therapy either early or late during TB treatment or after completion of TB treatment. Drug changes due to toxicity (defined as due to grade 3 or 4 adverse events) or virological failure (defined as viral load > 1000 copies/ml on two occasions, taken at least 4 weeks apart) were assessed in these patients. Results—A total of 501 TB-HIV co-infected patients were followed for a mean of 16.0 (95% confidence interval (CI): 15.5 to 16.6) months after antiretroviral therapy (ART) initiation. The standard first-line ARVs used, were efavirenz, lamivudine and didanosine. Individual drug switches for toxicity occurred in 14 patients (incidence rate: 2.1 per 100 person-years; 95% (CI): 1.1 to 3.5), and complete regimen changes due to virological failure in 25 patients (incidence rate: 3.7 per 100 person-years; CI: 2.4 to 5.5). The most common treatment limiting toxicities were neuropsychiatric effects (n=4; 0.8%), elevated transaminase levels and hyperlactatemia (n= 3; 0.6%), and peripheral neuropathy (n=2; 0.4%). Complete regimen change due to treatment failure was more common in patients with CD4+ cell count <50cells/mm3 (p<0.001) at ART initiation and body mass index greater than 25 kg/m2 (p=0.01) at entry into the study. Conclusion—Both drug switches and complete regimen change were uncommon in patients cotreated for TB-HIV with the chosen regimen. Patients with severe immunosuppression need to be monitored carefully, as they were most at risk for treatment failure requiring regimen change.
Early experiences with Isoniazid Preventive Therapy roll-out in an ART programme : a pharmacist's perspective.
(2016) Maharaj, Bhavna.; Yende-Zuma, Fortunate Nonhlanhla.; Naidoo, Anushka.; Gengiah, Santhanalakshmi.; Naidoo, Kogieleum.
Tuberculosis (TB) remains the leading cause of mortality amongst people infected with Human Immunodeficiency Virus (HIV). Additionally, TB recurrence after successful treatment completion occurs more frequently amongst HIV positive people. Isoniazid provided as part of isoniazid preventive therapy (IPT) has been the gold standard of TB preventive therapy provision for the last few decades. IPT has been recommended by the World Health Organisation (WHO) and implemented by national health programmes in countries across the world. Despite global efforts and campaigns to promote IPT, uptake still remains a challenge and, progress in the operational scale- up of IPT is slow. Both international and in-country guidelines have advanced to recommending the use of IPT in HIV infected patients who have previously been treated for TB because these patients remain at risk for recurrent TB especially in TB endemic settings. However, there still remains a paucity in data on the successful programmatic use of IPT secondary to previous cured TB among HIV infected patients and is the focus of the current analysis from a pharmacists’ perspective. Methods: A retrospective secondary analysis was conducted from October 2009 to October 2013, amongst HIV infected patients, previously treated for TB, accessing HIV care at the urban CAPRISA clinical research clinic in Durban, South Africa. The aim of the study was to evaluate the implementation of Isoniazid Preventive Therapy (IPT) within the parent study titled “TB recurrence upon treatment with HAART” (TRuTH). Data was collected on IPT uptake, course completion, drug toxicity, treatment interruption, and the occurrence of incident TB either during treatment or post IPT completion. The multidisciplinary team approach in providing IPT to at risk HIV infected patients, including the specific role of the pharmacist, was also assessed. Results: There were 402 patients enrolled in the parent study. Of these 344 (85.6%) were eligible to receive IPT and of whom 212 (61.6%) initiated IPT. Among those that commenced IPT, 184 (86.8%) completed the six-month course, 24 (11.3%) permanently discontinued IPT and of these, 3.8% discontinued due to side effects. More women (n=130; 61.3%) were initiated on IPT (p=0.001) than men. Overall median adherence to IPT was 97.6% (IQR: 94.2 - 99.4). There were 22 cases of incident TB in this cohort: 13 occurred prior to IPT and nine after IPT (incidence rate ratio 0.67; 95% CI 0.29- 1.58; p=0.362). CONCLUSIONS: Overall, we demonstrated a successful IPT roll-out in a high TB endemic setting with good uptake of IPT, minimal course interruptions or side effects reported. IPT is a safe and tolerable TB prevention intervention within ART programmes and importantly amongst patients on ART with previous TB treatment experience. The pharmacist played an important role in continuum of care in IPT provision within an ART programme. This role included ensuring stable supply chain management, supporting clinic staff in monitoring safe IPT use and provided data on IPT course completion rates
Effect of rifampicin and efavirenz on moxifloxacin concentrations when co-administered in patients with drug-susceptible TB.
(Oxford University Press., 2017) Naidoo, Anushka.; Chirehwa, Maxwell.; McIlleron, Helen.; Naidoo, Kogieleum.; Essack, Sabiha Yusuf.; Yende-Zuma, Fortunate Nonhlanhla.; Kimba-Phongi, Eddy.; Adamson, John.; Govender, Katya.; Padayatchi, Nesri.; Denti, Paolo.
Abstract available in pdf.
The effect of timing of initiation of antiretroviral therapy on loss to follow-up in HIV-tuberculosis coinfected patients in South Africa: an open-label, randomized, controlled trial.
(Wolters Kluwer Health., 2016) Yende-Zuma, Fortunate Nonhlanhla.; Naidoo, Kogieleum.
Abstract available in PDF file.
Ex vivo HIV entry into blood CD4+ T cells does not predict heterosexual HIV acquisition in women.
(Public Library of Science., 2018) Joag, Vineet.; Sivro, Aida.; Yende-Zuma, Fortunate Nonhlanhla.; Imam, Hajra.; Samsunder, Natasha.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; McKinnon, Lyle R.; Kaul, Rupert.
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.
High mortality rates in men initiated on anti-retroviral treatment in KwaZulu-Natal, South Africa.
(Public Library of Science., 2017) Naidoo, Kogieleum.; Hassan-Moosa, Razia.; Yende-Zuma, Fortunate Nonhlanhla.; Govender, Dhineshree.; Padayatchi, Nesri.; Dawood, Halima.; Adams, Rochelle Nicola.; Govender, Aveshen.; Chinappa, Tilagavathy.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.
Abstract available in pdf.
High rates of tuberculosis in patients accessing HAART in rural South Africa.
(Lippincott Williams & Wilkins., 2014) Naidoo, Kogieleum.; Abdool Karim, Quarraisha.; Bhushan, Ambika.; Naidoo, Kasavan.; Yende-Zuma, Fortunate Nonhlanhla.; Mchunu, Patricia K.; Fröhlich, Janet Ann.; Karim, Farina.; Upfold, Michele.; Kocheleff, Paul.; Abdool Karim, Salim Safurdeen.
Background: The challenge of early tuberculosis (TB) infection among rural patients accessing highly active antiretroviral therapy (HAART) in a resource-limited setting with high HIV and TB burden has not been fully quantified. Methods: This is a retrospective study nested within a prospective study of 969 patients consecutively initiated onto HAART at the CAPRISA AIDS Treatment programme in rural KwaZulu-Natal between January 2007 and December 2010. Patients were screened for clinical symptoms consistent with TB using a standardized checklist, and routine clinical investigations that included sputum microscopy and chest x-ray diagnosis. Results: Of 969 HIV-infected patients initiated on HAART, 173 [17.9%; 95% confidence interval (CI): 15.5 to 20.4] had active TB at HAART initiation. TB incidence rates were 3-fold higher in the first 3 months (early incident TB) after HAART initiation [11.5/100 person years (py); 95% CI: 7.1 to 17.5] compared with 4–24 months (late incident TB) post-HAART initiation (3.2/100 py; 95% CI: 2.2 to 4.5; incidence rate ratio: 3.6; 95% CI: 2.0 to 6.4; P , 0.001). Immune status of patients at HAART initiation did not impact TB incidence rates in patients with CD4+ counts of ,50 (5.3/100) and .200 (4.9/100 py; P = 0.81) cells per cubic millimeter. CD4+ count gains achieved 12 months post-HAART initiation were significantly different in patients with early incident TB versus late incident TB; P = 0.03. Conclusions: Rural HIV treatment programmes in TB-endemic settings experience high rates of TB irrespective of immunologic status of patients at HAART initiation, or duration on HAART.
HIV infection in high school students in rural South Africa: role of transmissions among students.
(Mary Ann Liebert, Inc., 2014) Kharsany, Ayesha Bibi Mahomed.; Buthelezi, Thulasizwe John.; Fröhlich, Janet Ann.; Yende-Zuma, Fortunate Nonhlanhla.; Samsunder, Natasha.; Mahlase, Gethwana.; Williamson, Carolyn.; Travers, Simon A.; Marais, Jinny C.; Dellar, Rachael Claire.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.
Abstract available in pdf.
Implementation of adolescent-friendly voluntary medical male circumcision using a school based recruitment program in rural KwaZulu-Natal, South Africa.
(Public Library of Science., 2014) Montague, Carl.; Ngcobo, Nelisiwe.; Mahlase, Gethwana.; Fröhlich, Janet Ann.; Pillay, Cheryl.; Yende-Zuma, Fortunate Nonhlanhla.; Humphries, Hilton Richard.; Dellar, Rachael Claire.; Naidoo, Kogieleum.; Abdool Karim, Quarraisha.
Background: Epidemiological data from South Africa demonstrate that risk of human immunodeficiency virus (HIV) infection in males increases dramatically after adolescence. Targeting adolescent HIV-negative males may be an efficient and cost-effective means of maximising the established HIV prevention benefits of voluntary medical male circumcision (VMMC) in high HIV prevalence-, low circumcision practice-settings. This study assessed the feasibility of recruiting male high school students for VMMC in such a setting in rural KwaZulu-Natal. Methods and Findings: Following community and key stakeholder consultations on the acceptability of VMMC recruitment through schools, information and awareness raising sessions were held in 42 high schools in Vulindlela. A three-phase VMMC demand-creation strategy was implemented in partnership with a local non-governmental organization, ZimnadiZonke, that involved: (i) community consultation and engagement; (ii) in-school VMMC awareness sessions and centralized HIV counselling and testing (HCT) service access; and (iii) peer recruitment and decentralized HCT service access. Transport was provided for volunteers to the Centre for the AIDS Programme of Research in South Africa (CAPRISA) clinic where the forceps-guided VMMC procedure was performed on consenting HIV-negative males. HIV infected volunteers were referred to further care either at the CAPRISA clinic or at public sector clinics. Between March 2011 and February 2013, a total of 5165 circumcisions were performed, the majority (71%) in males aged between 15 and 19 years. Demand-creation strategies were associated with an over five-fold increase in VMMC uptake from an average of 58 procedures/month in initial community engagement phases, to an average of 308 procedures/month on initiation of the peer recruitment-decentralized service phase. Post-operative adverse events were rare (1.2%), mostly minor and self-resolving. Conclusions: Optimizing a high volume, adolescent-targeted VMMC program was feasible, acceptable and safe in this setting. Adaptive demand-creation strategies are required to sustain high uptake.
Implementing isoniazid preventive therapy in a tuberculosis treatment-experienced cohort on ART.
(International Union against Tuberculosis and Lung Disease., 2017) Maharaj, Bhavna.; Gengiah, Tanuja Narayansamy.; Yende-Zuma, Fortunate Nonhlanhla.; Gengiah, Santhanalakshmi.; Naidoo, Anushka.; Naidoo, Kogieleum.
Abstract available in pdf.
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.
Modelling CD4 count and mortality in a cohort of patients initiated on HAART.
(2018) Mchunu, Nobuhle Nokubonga.; Mwambi, Henry Godwell.; Reddy, Tarylee.; Yende-Zuma, Fortunate Nonhlanhla.
Longitudinally measured data and time-to-event or survival data are often associated in some ways, and are traditionally analyzed separately (Asar et al., 2015). However, separate analyses are not applicable in this case because they may lead to inefficient or biased results. To remedy this, joint models optimally incorporate all available information (longitudinal and survival data) simultaneously (Wulfsohn & Tsiatis, 1997). Furthermore incorporating all sources of data improves the predictive capability of the joint model and lead to more informative inferences for the purpose of decision-making (Seyoum & Temesgen, 2017). The primary goal of this analysis was to determine the effect of repeatedly measured CD4 counts on mortality. The standard time-to-event models require that the time-dependent covariates of interest are external; where the value of the covariate at a future time point is not affected by the occurrence of the event. This requirement would not be fulfilled in this setting, since the repeatedly measured outcome is directly related to the mortality mechanism. Hence, a joint modeling approach was required. We applied the methods developed in this thesis to the CAPRISA AIDS Treatment program (CAT). We also sought to determine if the patients’ baseline BMI (Body mass index), baseline age, gender, baseline viral load, baseline CD8 count, baseline TB status and clinic site, influence the evolution of the CD4 count over time. Various linear mixed models were fitted to the CD4 count, adjusting for repeated measurements, as well as including intercept and slope as random effects. Different types of covariance structures were assessed and the spatial spherical correlation structure was found to be the best fit. The Cox PH model was employed to model mortality. Finally the joint model for longitudinal and time-to-event data was fitted. Out of the 4014 patients, 1457 (36.30%) were male. There were more patients presenting without TB at ART initiation, 3042 (75.78%) compared to those with prevalent TB, 972 (24.22%). Results from the multivariable random effects model showed that the patients gender, age, baseline viral load and baseline CD8 cell count had statistically significant influences on the rate of change in CD4 cell count over time. The un-adjusted and adjusted hazards regression both found CD4:CD8 ratio, viral load, gender and age of patients to be significant predictors of mortality. The result from the joint model in this study indicated that CD4 count change due to HAART and mortality had been influenced jointly by gender, age, baseline viral load, baseline CD8 count, time (in years) , CD4:CD8 ratio and by the interaction effects of time (in years) with TB status, baseline viral load and baseline CD8 cell count. CD4 count proved to be significantly associated with mortality, after adjusting for age, gender and other potential confounders Model diagnostics were performed for validating model assumptions, and our joint model fitted quite well with fairly good diagnostic attributes. The methods that were developed in this thesis were applied to the CAPRISA AIDS Treatment program (CAT) between June 2004 to December 2013.