Browsing by Author "Rusakaniko, Simbarashe"

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    A cluster randomised controlled trial protocol of an adapted intervention for alcohol use disorders in people living with HIV and AIDS : impact on alcohol use, general functional ability, quality of life and adherence to HAART
    (BioMed Central, 2017-01-28) Madhombiro, Munyaradzi; Dube-Marimbe, Bazondlile; Dube, Michelle; Chibanda, Dixon; Zunza, Moleen; Rusakaniko, Simbarashe; Stewart, David; Seedat, Soraya
    ENGLISH SUMMARY : Background: Interventions for alcohol use disorders (AUDs) in HIV infected individuals have been primarily targeted at HIV risk reduction and improved antiretroviral treatment adherence. However, reduction in alcohol use is an important goal. Alcohol use affects other key factors that may influence treatment course and outcome. In this study the authors aim to administer an adapted intervention for AUDs to reduce alcohol use in people living with HIV/AIDS (PLWHA). Methods: This study is a cluster randomised controlled trial at 16 HIV care clinics. A motivational interviewing and cognitive behavioural therapy based intervention for AUDs, developed through adaptation and piloted in Zimbabwe, will be administered to PLWHA with AUDs recruited at HIV clinics. The intervention will be administered over 16 sessions at 8 HIV clinics. This intervention will be compared with an equal attention control in the form of the World Health Organization Mental Health Gap Action Programme (WHO mhGAP) guide, adapted for the Zimbabwean context. General function, quality of life, and adherence to highly active antiretroviral treatment (HAART) will be secondary outcomes. Booster sessions will be administered to both groups at 3 and 6 months respectively. The primary outcome measure will be the Alcohol Use Disorder Identification Test (AUDIT) score. The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0), World Health Organisation Quality of Life (WHOQoL) HIV, viral load, and CD4 counts will be secondary outcome measures. Outcome assessments will be administered at baseline, 3, 6, and 12 months. Moderating factors such as perceived social support, how people cope with difficult situations and post-traumatic exposure and experience will be assessed at baseline. Trained research assistants will recruit participants. The outcome assessors who will be trained in administering the outcome and moderating tools will be blinded to the treatment arms allocated to the participants. However, the principal investigator, participants and intervention staff will be unblinded. Data will be analysed using STATA Version 14. Primary and secondary outcomes will be measured at four time points that is; at baseline, 3, 6, and 12 months respectively. All participants will be included in the analysis of primary and secondary outcome measures. The mean AUDIT scores will be compared between groups using student t-tests. Multilevel logistic regression analysis will be performed for binominal variables and multilevel linear regression for continuous variables. Descriptive statistics will be computed for baseline and follow-up assessments. Discussion: The study will be the first to address problematic alcohol use in PLWHA in Zimbabwe. It seeks to use local resources in delivering a modified, brief, evidence-based, and culturally contextualised intervention. The study results will determine the effectiveness of adapting psychological interventions for AUDs in HIV infected adults using a task-sharing framework.
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    Intervention for alcohol use disorders at an HIV care clinic in Harare : a pilot and feasibility study
    (BMC (part of Springer Nature), 2019) Madhombiro, Munyaradzi; Dube, Bazondlile; Dube, Michelle; Zunza, Moleen; Chibanda, Dixon; Rusakaniko, Simbarashe; Seedat, Soraya, 1966-
    Background: Alcohol use in HIV infected patients is associated with risky sexual behaviour, poor adherence to Highly Active Antiretroviral Therapy, treatment failure and increased physiologic harm. The objectives of the study were to pilot the outcome assessments to be used in the trial proper, assess the feasibility of delivery of a brief MI/CBT intervention compared to an WHO mhGAP intervention for problematic alcohol use in PLWH in Zimbabwe, and pilot the effectiveness (on alcohol use, functionality and CD4 count) of these interventions at 3 months in a randomised controlled trial design. Methods: An intervention for HIV infected patients with problematic alcohol use, developed through adaptation of existing evidence based psychological treatments, was assessed for its feasibility at a tertiary HIV care clinic in Zimbabwe. Registered general nurses, using a manualised protocol, delivered the intervention. Forty patients were recruited and randomised to receive either an MI/CBT intervention or the WHO mhGAP Intervention Guide for AUDs (n = 20 patients per group). Results: Out of 40 participants enrolled, 31 were successfully followed up for 3 months with a loss to follow-up rate of 23%. There was a statistically significant decrease in AUDIT score over time in both groups (p < 0.001), however no statistically significant group difference with a mean difference of 0.80, standard error of 2.07 and p = 0.70. For the CD4 count, the median and interquartile ranges at baseline for MI/CBT and WHO mhGAP IG groups were 218 (274) and 484 (211.50), respectively. At follow-up, median and interquartile ranges for the CD4 count for MI/CBT and WHO mhGAP IG groups were 390 (280) and 567 (378), respectively, indicative of improvement in immunological parameters in both arms. Conclusion: The findings from this pilot study suggests that a brief MI/CBT delivered by Registered General Nurses for problematic alcohol use is feasible in this population but will require the implementation of additional measures to improve retention. However, mechanisms to improve retention need special attention.
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    Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases
    (Public Library of Science, 2019-10-24) Katsidzira, Leolin; Vorster, Anna; Gangaidzo, Innocent T.; Makunike-Mutasa, Rudo; Govender, Dhiren; Rusakaniko, Simbarashe; Thomson, Sandie; Matenga, Jonathan A.; Ramesar, Raj
    Background: Approximately 25% of colorectal cancer patients in sub-Saharan Africa are younger than 40 years, and hereditary factors may contribute. We investigated the frequency and patterns of inherited colorectal cancer among black Zimbabweans. Methods: A population-based cross-sectional study of ninety individuals with a new diagnosis of colorectal cancer was carried out in Harare, Zimbabwe between November 2012 and December 2015. Phenotypic data was obtained using interviewer administered questionnaires, and reviewing clinical and pathology data. Cases were screened for mismatch repair deficiency by immunohistochemistry and/or microsatellite instability testing, and for MLH1, MSH2 and EPCAM deletions using multiplex ligation-dependent probe amplification. Next generation sequencing using a 16-gene panel was performed for cases with phenotypic features consistent with familial colorectal cancer. Variants were assessed for pathogenicity using the mean allele frequency, phenotypic features and searching online databases. Results: Three Lynch syndrome cases were identified: MSH2 c.2634G>A pathogenic mutation, c.(1896+1_1897–1)_(*193_?)del , and one fulfilling the Amsterdam criteria, with MLH1 and PMS2 deficiency, but no identifiable pathogenic mutation. Two other cases had a strong family history of cancers, but the exact syndrome was not identified. The prevalence of Lynch syndrome was 3·3% (95% CI 0·7–9·4), and that of familial colorectal cancer was 5·6% (95% CI, 1·8–12·5). Conclusions: Identifying cases of inherited colorectal cancer in sub-Saharan Africa is feasible, and our findings can inform screening guidelines appropriate to this setting.
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    Perceptions of alcohol use in the context of HIV treatment : a qualitative study
    (Dove Medical Press, 2018) Madhombiro, Munyaradzi; Marimbe-Dube, Bazondlile; Dube, Michelle; Kaiyo-Utete, Malinda; Paradzai, Angeline; Chibanda, Dixon; Rusakaniko, Simbarashe; Van Der Watt, A. S. J.; Seedat, Soraya
    Background: Alcohol use is associated with poor HIV treatment outcomes. This study aimed to understand patients’ perceptions of the impact of alcohol use in the context of HIV care. Methods: The study design was a descriptive qualitative study of HIV positive individuals receiving antiretroviral treatment. The study involved four focus group discussions with male and female participants at a tertiary center, city clinic, and rural church. We employed convenience sampling and invited patients coming for their routine visits and medication refills to participate. Results: Participants had an awareness of both the direct and indirect effects of alcohol use. The direct effects related to the incompatibility of HIV medication and alcohol. The indirect effects related to the negative impact of alcohol on treatment adherence. Participants proffered reasons why HIV infected individuals on HIV treatment drink and felt that patients had to make a deliberate choice to stop drinking. Participants displayed some knowledge of interventions for drinking cessation and highlighted the use of pharmacological interventions to stop drinking. Participants indicated that they preferred HIV counselors to provide counseling services in view of the existing relationships that patients had with counselors. Conclusion: People living with HIV have adequate knowledge of the effects of alcohol use in the context of HIV treatment. Stigma and the time taken to engage in an alcohol use intervention appeared to be the main impediments to uptake. The current model of HIV treatment, based on trust with the HIV care team, and maintenance of this trust, could bolster the uptake of an intervention. Involvement of HIV patients in their treatment is necessary to improve treatment outcomes in the context of alcohol use.
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    Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe
    (BMC, 2021-05-24) Ngara, Bernard; Zvada, Simbarashe; Chawana, Tariro D.; Nhachi, Charles F. B.; Rusakaniko, Simbarashe
    Background: Drug potency is a pharmacological parameter defining dose or concentration of drug required to obtain 50% of the drug’s maximal effect. Pharmacokinetic-pharmacodynamic modelling and simulation allows estimation of potency and evaluate strategies improving treatment outcome. The objective of our study is to determine potency of atazanavir in hair, defined as atazanavir level in hair associated with 50% probability of failing to achieve viral load below 1000 copies/ml among adolescents, and explore the effect of participant specific variables on potency. Methods: A secondary analysis was performed on data from a previous study conducted in HIV-infected adolescents failing 2nd line ART from Harare central hospital, Zimbabwe, between 2015 and 2016. We simulated atazanavir concentrations in hair using NONMEM (version 7.3) ADVAN 13, based on a previously established pharmacokinetic model. Logistic regression methods were used for PKPD analysis. Simulations utilising PKPD model focused on estimation of potency and exploring the effect of covariates. Results: The potency of atazanavir in hair was found to be 4.5 ng/mg hair before adjusting for covariate effects. Participants at three months follow-up, reporting adequate adherence, having normal BMI-for-age, and cared for by mature guardians had increased potency of atazanavir in hair of 2.6 ng/mg, however the follow-up event was the only statistically significant factor at 5% level. Conclusion: Atazanavir in hair in the range 2.6 to 4.5 ng/mg is associated with above 50% probability of early viral load suppression. Adherence monitoring to adolescents with lower potency of atazanavir is recommended. The effect self-reported adherence level, BMI-for-age, and caregiver status require further evaluation.
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    A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir : a study of HIV-infected Zimbabwean adolescents
    (BMC, 2020-08-03) Ngara, Bernard; Zvada, Simbarashe; Chawana, Tariro Dianah; Stray-Pedersen, Babill; Nhachi, Charles Fungai Brian; Rusakaniko, Simbarashe
    Background: Adolescents experience higher levels of non-adherence to HIV treatment. Drug concentration in hair promises to be reliable for assessing exposure to antiretroviral (ARV) drugs. Pharmacokinetic modelling can explore utility of drug in hair. We aimed at developing and validating a pharmacokinetic model based on atazanavir/ ritonavir (ATV/r) in hair and identify factors associated with variabilities in hair accumulation. Methods: We based the study on secondary data analysis whereby data from a previous study on Zimbabwean adolescents which collected hair samples at enrolment and 3 months follow-up was used in model development. We performed model development in NONMEM (version 7.3) ADVAN 13. Results: There is 16% / 18% of the respective ATV/r in hair as a ratio of steady-state trough plasma concentrations. At follow-up, we estimated an increase of 30% /42% of respective ATV/r in hair. We associated a unit increase in adherence score with 2% increase in hair concentration both ATV/r. Thinner participants had 54% higher while overweight had 21% lower atazanavir in hair compared to normal weight participants. Adolescents receiving care from fellow siblings had atazanavir in hair at least 54% less compared to other forms of care. Conclusion: The determinants of increased ATV/r concentrations in hair found in our analysis are monitoring at follow up event, body mass index, and caregiver status. Measuring drug concentration in hair is feasibly accomplished and could be more accurate for monitoring ARV drugs exposure.