The global commitment by governments throughout the world to scaling up access to Antiretroviral Therapy (ART) in response to the crisis imposed by the HIV epidemic has resulted in a large number of people living with Human Immune-deficiency Virus (HIV) worldwide. According to statistics provided by the World Health Organization (WHO), there were approximately 35 million people living with HIV (PLWHIV) in 2012.1This large number of PLWHIV observed in recent years reflects the life-prolonging benefit effects of ART. / Dissertation (MSc)--University of Pretoria, 2014. / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted

Introduction: Medicines are an important component of any health system. Even though the importance of medicines in the health system is indisputable, one of the major concerns remains the risk of adverse drug reactions when used by consumers. Adverse drug reactions place a burden on the healthcare system, usually as a result of complications requiring hospital admission or extended hospital admissions. In Africa, about 28.6% of adverse drug reactions reported in Africa were due to antiretroviral therapy. Recently, the adoption of the “test and treat” policy by the World Health Organisation increased the number of people receiving antiretroviral therapy. Therefore, this systematic review was conducted to explore the magnitude of antiretroviral therapy-related adverse drug reactions hospitalisations, and mortalities in the region, following the increase in people initiating therapy, and the implications to the service delivery component of the healthcare system. Methods: In March 2021, PubMed, EBSCOHost, and SCOPUS, databases were systematically searched for appropriate articles. The selection of articles was based on predefined inclusion and exclusion criteria. Data from included articles were extracted as per a set of defined criteria into a data extraction form. A meta-analysis was done using Stata package software 15.0 using Stata “metaprop” command. Results: The pooled prevalence of adverse drug reactions hospitalisations in all studies was 26.5% (95% confidence interval:18.4,35.4) and that of mortality was 6.1% (95% confidence interval:2.1,11.7). The most prevalent adverse reactions reported include hepatotoxicity, kidney injury, lactic acidosis, skin, neurologic, and hematologic reactions. The antiviral implicated, are non-nucleoside reverse transcriptase inhibitors, nucleoside/tide reverse transcriptase inhibitors, and protease inhibitors. The pediatric population was underrepresented as only two studies included pediatric patients. The economic impact of adverse reactions was impossible to estimate, as only one study reported on financial implications. Conclusion: Antiretroviral therapy-related adverse reactions hospitalisations and mortalities have a high prevalence in Africa. There are concerns about age-related morbidities and lifestyle diseases as risk factors related to adverse reactions. To adequately combat adverse reactions associated with antiretrovirals, African country health systems need multidisciplinary actions to strengthen strategies for prediction, identification, reporting, and prevention of adverse reaction occurrence.

Despite widespread availability of effective antiretroviral therapy (ART), people living with HIV (PWH) remain at risk of developing comorbidities including HIV-associated neurocognitive impairment (H-NCI). These individuals may then be at an increased risk for treatment non-adherence, which leads to poor quality of life and early mortality. Despite this risk, there is a paucity in trained professionals in low- and middle-income countries with appropriate knowledge and skills to identify H-NCI and make appropriate referrals for additional confirmatory testing or intervention, depending on the severity and context of the screening. General medical doctors, nurses and adherence counsellors provide most HIV related healthcare services at a primary healthcare level in South Africa. However, awareness of the clinical presentation of H-NCI, and their current screening practices among these cadres, is unclear. To address these knowledge gaps this thesis set out to explore the following aims (1) examine existing H-NCI knowledge and practices among healthcare workers delivering HIV services in South Africa, (2) develop an appropriate H-NCI training programme for primary healthcare workers, and (3) lastly, pilot the H-NCI training to determine whether H-NCI screening would be feasible at a primary healthcare level in South Africa. Methods To achieve these objectives, the study was divided into two phases. In phase one, a scoping review identified and summarised published studies addressing brain and/or behaviour training approaches, including H-NCI, targeting frontline HIV healthcare workers in Africa. An online survey was developed and administered to examine existing H-NCI knowledge and current practices among healthcare workers providing HIV services in South Africa. Focus group discussions and in-depth interviews were then conducted to explore knowledge gaps, previous H-NCI training and healthcare workers' perspectives of screening at a primary healthcare level. In phase two, an H-NCI training curriculum was developed and a work-integrated H-NCI training programme targeting primary healthcare workers was piloted. The pilot training assessed knowledge of H-NCI signs and symptoms, healthcare workers' attitude toward and comfort with H-NCI screening tools and healthcare workers ability to accurately administer an H-NCI screening tool. The assessments were repeated two months post-training to evaluate retention of knowledge and skills. Results The scoping review of the existing literature suggested that there were few brain and/ or behaviour training programs targeting healthcare workers providing HIV services in Africa. Of the ten studies identified in the scoping review, one study included H-NCI in the training curriculum. The online survey found that H-NCI knowledge was limited and screening practices virtually non-existent among healthcare workers providing HIV care in South Africa. Qualitative data gathered during the focus group discussions and the in-depth interviews provided greater insight on the existing knowledge and practices gaps as well as highlighting that healthcare workers had not received training on H-NCI. The results from the qualitative investigations showed that primary healthcare workers were in favour of receiving such training. Overall, knowledge of H-NCI improved among primary healthcare workers following the work-integrated H-NCI training programme. The training demonstrated that primary healthcare workers providing clinical services, such as medical doctors or professional nurses were able to administer an H-NCI screening tool. Although knowledge of the clinical presentation of H-NCI improved among adherence counsellors, these healthcare workers experienced challenges in administering the H-NCI screening tool. Conclusion As a body of work, the findings from this thesis suggest that healthcare professionals providing HIV services in South Africa have limited knowledge to identify H-NCI, and screening practices are uncommon. Although training revealed differences between cadres in administering screening tools, healthcare workers providing clinical care, including general medical doctors and professional nurses, may be able to provide H-NCI screening at routine annual visits. Although adherence counsellors are ideally situated in the clinic flow to provide targeted screening by flagging clinical presentation of H-NCI among PWH accessing care, this cadre will require additional training, mentorship and support to successfully administer H-NCI screening tools. However, the feasibility of H-NCI screening at a primary healthcare, timing and nature of any screening remains to be explored. This body of work is a step toward increasing the availability of skilled healthcare workers with appropriate knowledge and skills to screen and identify H-NCI in low- and middle-income countries. The work presented in this thesis provides a foundation for further development of the H-NCI training module and future investigations examining targeted screening strategies at a primary healthcare level, feasibility and access to existing interventions post-screening

Southern Africa has the highest prevalence of HIV worldwide, and South Africa has the highest number of HIV infected people. South Africa and other resource-limited countries provide antiretroviral therapy (ART) for people with HIV, with limited, standardized regimens for first line and second line. Patients who fail first line treatment are put on second line regimens, yet options for third line are very limited. The first study looks at predictors of first line treatment failure in South Africa and develops a predictive model that can estimate absolute risk of treatment failure over 5 years on ART, given a baseline profile of clinical and demographic factors. The model was developed with accelerated failure time models, using predictors that maximized discrimination between patients. The model can be used to identify patients who need adherence interventions, and to estimate how changes in baseline parameters in the population influence long-term need for second line ART. The second study explores whether delays from detection of first line treatment failure until second line treatment initiation, which are widespread in South Africa, decrease the effectiveness of second line ART. Marginal structural models were used to include patients who never switched to second line after failure in analysis. This study shows that, despite potency of second line drugs, short delays in second line among very sick patients can lead to worse outcomes. These findings may be due to drug resistance, immune system damage, and/or lack of adherence to medication. The third study examines whether switch in type of NRTI (nucleoside reverse transcriptase inhibitor, which is a drug class used in both first and second line regimens) from first line to second line improves outcomes on second line ART. While a switch in NRTI is recommended by treatment guidelines, it cannot always occur due to contraindications to some NRTIs. Using clinical data from South Africa and Zambia and adjusting for propensity scores, we see that switching from zidovudine in first line to a different NRTI in second line leads to less treatment failure on second line, suggesting that NRTI resistance may play a role in second line outcomes.

This study compare immunological and virological outcomes in antiretroviral therapy naïve patients exposed to Isoniazid prevention treatment.Medical records of antiretroviral naïve patients managed in the public sector from 1st January 2006 to 31st December 2006 were analysed.Multivariate analysis of variance showed that each treatment group achieved statistically significant increases in CD4+ cell count and viral load decay at each follow-up time point. Pairwise post hoc contrast tests showed patients in NVPipt-past group and EFVipt-past group to have superior immunological and virological outcomes respectively. / Health Studies / M.A. (Public health)

Thesis (MPH.) --University of Limpopo, 2018 / Background: The prevalence of HIV in South Africa has increased largely due to the combined effect of new infections, and a successfully expanded antiretroviral treatment programme, which has increased survival among people living with HIV. As the up-scaling of patients on ART has been increased, the aim of the current study was to investigate the variations of the clinical outcomes between patients initiated with CD4 < 350 and of those above 350 after the implementation of the new eligibility criteria for ARV therapy. Methods The current study used quantitative approach to retrospectively review a total of 488 records of adult patient who were registered in health facilities which were purposefully sampled from Sekhukhune District of Limpopo Province. SPSS version 23.0 was used to analyse data. Results Approximately 60% of the patients initiated on ART were having CD4 count <350 and male patients were more at 74% as compared to females at 54.7%. Patients who started ART with a baseline CD4 >350 had a high rate of lost to follow up within 3 months after start of ART at 15% than those with a baseline CD4 <350 at 10.2. More patients were lost to follow-up shortly after starting treatment at 3 months at an average of 13.8% in both CD4 counts. Majority of patients retained in care were those who started ART treatment with a baseline CD4<350 at 87.4%. Viral load completion rate at 12 months was higher than that of 6 months, at 86.8 and 80.5 respectively. Patients with a baseline CD4 >350 suppressed more than those who started ART with a baseline CD4 <350 at both 6 and 12 months at >90% suppression rate. Lastly, most of the patients died within 3 months of ART treatment and had a baseline CD4 < 350 than at 2.4% those with a baseline CD4 >350 at 0.6%. Conclusions The implementation of the new eligibility criteria of ART initiation improves the clinical outcome of patients on ART. There are still patients that are missed to be monitored viral load bloods which play a key role in determining the clinical outcomes of patients. Clinicians and nurses should adhere to the recommended time frames for monitoring of ART patients to improve clinical outcomes. Keywords: HIV/AIDS, antiretroviral therapy, clinical outcome, ART initiation; Eligibility Criteria;

This study compare immunological and virological outcomes in antiretroviral therapy naïve patients exposed to Isoniazid prevention treatment.Medical records of antiretroviral naïve patients managed in the public sector from 1st January 2006 to 31st December 2006 were analysed.Multivariate analysis of variance showed that each treatment group achieved statistically significant increases in CD4+ cell count and viral load decay at each follow-up time point. Pairwise post hoc contrast tests showed patients in NVPipt-past group and EFVipt-past group to have superior immunological and virological outcomes respectively. / Health Studies / M.A. (Public health)

Master of Public Health - MPH / Background: Zimbabwe has one of the highest HIV prevalence rates in sub-Saharan Africa, with the adult prevalence rate at 15%. The HIV prevalence is highest among adult women, at 18%. Mother-to-child transmission is the second leading cause of HIV in Zimbabwe. Therefore, provision of anti-retroviral therapy to pregnant women is important in reducing mother-to-child transmission. In 2012, the World Health Organisation formally adopted ART guidelines known as "Option B Plus", where triple therapy is provided to pregnant women for life, regardless of CD4 count. Zimbabwe subsequently adopted Option B Plus in September 2013. However, the success of ART depends on adherence to treatment. Lack of adherence to treatment leads to an increased risk of opportunistic infections and drug resistance, which is costly to treat. The aim of the study was to explore pre-and post-partum barriers to anti-retroviral therapy for HIV-positive women initiated onto Option B Plus in Harare, Zimbabwe. Methodology: Descriptive qualitative methods were used to explore the barriers to ART adherence for pre-and post-partum HIV-positive women initiated onto Option B Plus in Harare, Zimbabwe. In-depth, semi-structured interviews were conducted in Shona with 20 non-adherent pre-and post-partum HIV-positive women and four key informants who are health workers from two identified health facilities (Edith Opperman Polyclinic and Kuwadzana Polyclinic). The interviews were recorded, transcribed and translated into English. The data was analysed using inductive thematic analysis. Results: Health facility and individual factors emerged as barriers to adherence. Heavy workload and staff shortages, negative health worker attitude, cost of accessing health facilities, medicine shortages and detrimental health facility policies were all health facility related barriers identified by both key informants and the women. Individual barriers were related to difficulty in navigating the early days after diagnosis and treatment, stigma, intimate partner dynamics and religion. Conclusion: Despite free, decentralised provision of ART, barriers to adherence still exist. Many of the barriers have been articulated in previous research that focused on prevention of- mother-to-child transmission regimens, as well as ART regimens for the general population. The fact that the barriers remain suggests that the barriers are complex and addressing them will require tackling social constraints such as stigma and gender roles that pose a significant barrier to adherence.

Poor decision making among clinicians to transferring human immune deficiency virus (HIV) patients into second-line antiretroviral therapy (ART) has led to an increase in morbidity and mortality to people living with HIV (PLHIV). No clear barriers are known for clinicians not switching their patients. This is a descriptive qualitative research aimed to discover obstacles that influence clinicians' decision making to transferring patients into second-line ART despite higher level resistance to first-line ART. The researcher applied a participatory action research framework to solve the identified barriers with clinicians. Using the research questions the researcher explored reasons, perceived barriers and enabling factors for clinicians delay in making decision to transferring HIV patients into second-line ART. In-depth semistructured interviews were conducted with 30 participants. Six thematic areas (a) clinicians' capacity to diagnose treatment failure, (b) laboratory investigations, (c) availability, access, and tolerability to second-line ART, (d) clinicians' perceptions on ARV medicines, (e) clients' readiness for ARV medicines, and (f) adherence and retention to ARV medicines were analysed using STATA. Readiness, adherence and retention to ART, knowledge, competence and experience on ART , lack of viral load testing, and shortage of second-line ART were the common major barriers for clinicians in determining transferring patients into second-line ART. The government of Tanzania should acknowledge and create participation, responsibility, and commitment strategies to reduce the observed barriers. Findings of this study generates knowledge and provide actionable plans to help clinicians easily identify HIV patients who are in need of second-line ART.

The purpose of this study was to explore and describe the determinant factors affecting adherence to antiretroviral therapy among HIV infected patients in Addis Ababa, Ethiopia. A cross-sectional study design was used and data were collected by interviewing 290 study participants from two health facilities using structured questionnaire. The research finding revealed 80.0% of the study participants had optimal combined adherence to dose, schedule and dietary instructions in the past three days. And, the non adherence rate was 20.0%. In multivariate analysis only WHO clinical stage, change of ARV medication, knowledge about HIV disease and ART, and use of reminders were found to be independently associated with adherence to antiretroviral therapy. The most common reasons for missing HIV medications in the past one month were forgetfulness (35.1%), being busy with other things (17.5%), and running out of pills (10.5%). Adherence improving interventions should be emphasized to address multi-faceted problems. This study recommends setting of convenient appointment schedule, disclosure of one's HIV status, maintaining confidentiality of patient-related information, enhancing patient-provider relationship, use of reminders including SMS text messages, and engagement of PLHIV in adherence improving interventions through peer support, and providing regular health education to the PLHIV to improve adherence of patients to ART / Health Studies / M.A. (Public Health)