Indiana University-Purdue University Indianapolis (IUPUI) / Background: Many authors have indicated that HIV-infected patients mortality risk is higher immediately following the start of Antiretroviral Therapy. However, mortality rate of HIV-infected patients is expected to decrease after starting Antiretroviral Therapy (ART) potentially complicating accurate statistical estimation of patient survival and, more generally, effective monitoring of the evolution of the worldwide epidemic. Method: In this thesis, we determine if mortality of HIV-patients increases or decreases after the initiation of ART therapy using flexible survival modelling techniques. To achieve this objective, this study uses semi-parametric statistical models for fitting and estimating survival time using different covariates. A combination of the Weibull distribution with splines is compared to the usual Weibull, exponential, and gamma distribution parametric models, and the Cox semi-parametric model. The objective of this study is to compare these models to find the best fitting model so that it can then be used to improve modeling of the survival time and explore the pattern of change in mortality rates for a cohort of HIV-infected patients recruited in a care and treatment program in Uganda. Results: The analysis shows that flexible survival Weibull models are better than usualoff-parametric and semi-parametric model fitting according to the AIC criterion. Conclusion: The mortality of HIV-patients is high right after the initiation of ART therapy and decreases rapidly subsequently.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of MSc (Med) Johannesburg, 2011 / Peripheral sensory neuropathy is a common neurological complication of antiretroviral therapy, typically occurring within 6-months of starting Highly Active Antiretroviral Therapy (HAART) which includes stavudine. Therefore, the primary aim of the study was to determine the 6-month incidence of ATN in patients free of neuropathy and beginning stavudine-based HAART for the first time. Also, we examined whether initiating stavudine-based HAART altered the symptoms of patients who had a pre-existing, virus-mediated distal symmetrical polyneuropathy (HIV-DSP). Seventy-five HIV-positive patients were screened for neuropathy, at the Chris-Hani Baragwanath Hospital, using the AIDS Clinical Trials Group neuropathy screening tool. The bilateral presence of atleast one sign (decreased vibration sense in the great toe or absent ankle reflex) and one symptom (pain, paraesthesia or numbness) in the feet was indicative of neuropathy. On recruitment, 52 patients presented without neuropathy and 13 patients presented with HIV-DSP. After 3- months of follow-up (n=46), 23% (10/46) of patients had developed peripheral neuropathy, and by 6-months (n=44), 41% (18/44) of patients had developed neuropathy. Greater disease severity was the only risk factor significantly associated with the development of neuropathy. Eleven (61%) of the 18 patients that developed neuropathy, developed painful symptomatic neuropathy, and only 6 (55%) of these patients were receiving treatment for symptom relief. In patients with HIV-DSP, numbness was the most common symptom reported at baseline and was the only symptom to reduce in frequency across the 6-months. In conclusion, we found that the development of neuropathy is common in the first 6-months of patients initiating stavudine-based HAART.

The Human Immunodeficiency Virus (HIV) which causes Acquired Immunodeficiency Syndrome (AIDS) has caused a global scare with mainly poor African countries suffering the greatest burden. Treatment of HIV is more of palliation rather than cure such that there is no room for treatment interruption if treatment goals are to be met. Antiretroviral treatment is associated with short term and long term side effects which have the potential to negatively impact on the high levels of adherence to treatment that is required to maintain virological suppression and may eventually lead to development of drug resistance and treatment failure. This research aims to identify the extent to which these side effects, through possible poor adherence, impact on treatment successes by measuring the risk that side effects contribute towards treatment failure. Methods Secondary data analysis was conducted on a cohort of patients who initiated ART between 2004 and 2010 at a large tertiary facility in Johannesburg. Patients who were switched to second line ART due to treatment failure were identified. Assessment of side effects on adherence was done. The hazards of side effects among patients switching and not switching to second line were calculated using Cox proportional hazards regression adjusting for other socio-demographic and clinical predictors for treatment failure. Interaction between side effects, gender, age and that of side effects and adherence was investigated. Time dependent covariates were also investigated. Confounding was controlled using multivariate Cox regression analysis. Results There were 5285 patients in the baseline cohort with multiple entry points who contributed 16035 person-years of follow up. The cohort consisted of 63.2% females and 36.8% males. Of these 85.9% were initiated on stavudine (d4T)- based regimen, 7.1% on tenofovir (TDF), 6.3% on zidovudine (AZT)-based regimen and 0.7% on other regimens. The median and mean time at risk per subject was 2.2 and 2.3 years respectively. A total of 770 episodes of side effects due to first line ART were experienced with some patients recording multiple side effects at different time points. Adherence data were found to be missing and incoherent in some of the regimen dosages and could not be used to objectively compare patients. There were 430 patients who were switched to second line ART due to treatment failure. Relative to the group of no side effects, the adjusted hazard ratios for mild, moderate and severe side effects were 1.40 (95% CI=0.94-2.09) p=0.10; 1.72 (95% CI=1.35-2.20) p<0.01 and 1.24 (95% CI=0.65-2.35) p=0.52 respectively. Therefore, overally side effects did not seem to play a role in the time to switch to second line ART. Sex, baseline CD4 cell count, the period during which ART was initiated and the time between date of testing HIV positive and date of initiating were significantly associated with the time to switching to second line ART. Conclusion The study informs that side effects overally may not play a significant role in switching patients from first line to second line ART with the exception of moderate side effects. However, patients who experience side effects should be closely monitored and adequately counselled to help them cope with the side effects so that optimal adherence levels are maintained. Availability of adherence scores or additional information on pills that should have been taken on periods during which pills were reported to have been missed would have made the research more valuable by allowing objective comparison of adherence among patients.

The roll-out of antiretroviral drugs in South Africa started in March 2004. In Mopani district, a rural district of Limpopo Province, the roll-out programme commenced in October 2004. While many resources were invested in this program, no study has assessed the clinical outcomes in this rural district. In addition, most studies conducted in South Africa were conducted in urban and tertiary settings. Assessing clinical outcomes is important in determining whether the program is making the desired clinical difference in the lives of the patients and may serve as feedback into the program for quality improvement purposes. Methodology The study was a retrospective record review of patients who were initiated on antiretroviral (ARV) treatment between December 2007 and November 2008. A structured questionnaire was used to collect data from 124 patient’s files and data was collected up to November 2011. The data collected included patients’ socio-demographic characteristics, clinical outcomes (CD4 count, viral load, presence of opportunistic infections, adverse effects and hospital admissions recorded at 6, 12, 24 and 36 months), the number of patients who were still attending the ARV clinic at 36 months and the reasons why patients are no longer attending the clinic. Data was analysed with Epi-Info and STATA. Results Of the 124 patients, 69% were females, 28% males and 3% did not have their sex specified. The majority of the patients were between 30 and 49 years. There was a significant improvement in CD4 count and viral load between baseline and all timeperiods after the initiation of ARV treatment. The mean CD4 count at baseline was 128The roll-out of antiretroviral drugs in South Africa started in March 2004. In Mopani district, a rural district of Limpopo Province, the roll-out programme commenced in October 2004. While many resources were invested in this program, no study has assessed the clinical outcomes in this rural district. In addition, most studies conducted in South Africa were conducted in urban and tertiary settings. Assessing clinical outcomes is important in determining whether the program is making the desired clinical difference in the lives of the patients and may serve as feedback into the program for quality improvement purposes. Methodology The study was a retrospective record review of patients who were initiated on antiretroviral (ARV) treatment between December 2007 and November 2008. A structured questionnaire was used to collect data from 124 patient’s files and data was collected up to November 2011. The data collected included patients’ socio-demographic characteristics, clinical outcomes (CD4 count, viral load, presence of opportunistic infections, adverse effects and hospital admissions recorded at 6, 12, 24 and 36 months), the number of patients who were still attending the ARV clinic at 36 months and the reasons why patients are no longer attending the clinic. Data was analysed with Epi-Info and STATA. Results Of the 124 patients, 69% were females, 28% males and 3% did not have their sex specified. The majority of the patients were between 30 and 49 years. There was a significant improvement in CD4 count and viral load between baseline and all timeperiods after the initiation of ARV treatment. The mean CD4 count at baseline was 128 The roll-out of antiretroviral drugs in South Africa started in March 2004. In Mopani district, a rural district of Limpopo Province, the roll-out programme commenced in October 2004. While many resources were invested in this program, no study has assessed the clinical outcomes in this rural district. In addition, most studies conducted in South Africa were conducted in urban and tertiary settings. Assessing clinical outcomes is important in determining whether the program is making the desired clinical difference in the lives of the patients and may serve as feedback into the program for quality improvement purposes. Methodology The study was a retrospective record review of patients who were initiated on antiretroviral (ARV) treatment between December 2007 and November 2008. A structured questionnaire was used to collect data from 124 patient’s files and data was collected up to November 2011. The data collected included patients’ socio-demographic characteristics, clinical outcomes (CD4 count, viral load, presence of opportunistic infections, adverse effects and hospital admissions recorded at 6, 12, 24 and 36 months), the number of patients who were still attending the ARV clinic at 36 months and the reasons why patients are no longer attending the clinic. Data was analysed with Epi-Info and STATA. Results Of the 124 patients, 69% were females, 28% males and 3% did not have their sex specified. The majority of the patients were between 30 and 49 years. There was a significant improvement in CD4 count and viral load between baseline and all timeperiods after the initiation of ARV treatment. The mean CD4 count at baseline was 128 cells/mm3; it increased to 310 cells/mm3 at 6 months, 380 cells/mm3 at 12 months and 470 cells/mm3 at 24 months. By 6 months, 67% of the patients had achieved viral suppression, but at 24 months, patients started having viral rebound. During the study, 20 patients fell pregnant and four patients fell pregnant twice. Overall, pregnant patients had a significantly higher viral load compared to non-pregnant patients (p-values = 0.015 at 6 months, 0.002 at 12 months and 0.027 at 24 months). Seventy two percent of patients were retained in the program at 36 months. Of the 28% that were no longer attending the clinic, 11.3% were transferred to other institutions, 6.5% were down referred to clinics, 3.2% died, 3.2% defaulted and 3.2% were lost to follow-up. Conclusion This study shows that good clinical outcomes can be achieved within an antiretroviral rollout program in a rural hospital. The biggest magnitude of clinical benefits was observed in the first six months after the initiation of ARV treatment with threats of viral rebound thereafter. There was good patient retention at 36 months after initiation of ARV treatment and a significant difference in viral load between pregnant and non-pregnant patients. The high rate of unplanned pregnancy signifies the need to place closer attention to family planning among female patients on antiretroviral treatment.

Carcinoma of the cervix is frequently diagnosed in the department of Radiation Oncology in Charlotte Maxeke Johannesburg Academic Hospital(CMJAH). It is therefore is a condition of priority and there is scarce literature in the management of HIV positive patients. OBJECTIVES: The primary objective of the research is to determine the overall survival of 2yrs and more, as well as to determine acute and late toxicity for patients completing prescribed radiation treatment. The secondary objective was to determine the impact of highly active antiretroviral therapy on survival and toxicity. The study is limited to HIV positive women presenting with cervical cancer. DESIGN & METHOD: The study is a retrospective study of patients treated at Charlotte Maxeke Johannesburg Academic Hospital between 2008-2009. Inclusion criteria: Females between the ages of 18 and 70, Stages IB2 – Stage IIIB carcinoma of the cervix who have completed planned radiation therapy with or without chemotherapy. The sample size was 151 patients. RESULTS: The mean age was 42.7yrs. The median CD4 count was 309 and 26.2% had CD4 counts below 200.The majority of patients had either Stage IIB (55.0%) or IIIB (31.8%). The total dose to Point A was a median dose of 74Gy. The majority of patients had either Grade II (38.4%) or III (31.1%) toxicity. Significant association between these adverse events and HAART status was rated as p=0.0008. The most common late complication was cystitis (15.9%). Overall survival at 2 years was 100% for Stage I, 92.8% for Stage II and 96% for Stage III. CONCLUSION: The median age was lower than in the HIV negative patients. The acute complications for those not on HAART, were higher in comparison to patients on HAART. The overall survival at 2 yrs. was above 90% for all stages in this study / GR2018

No description available.

Background: Tenofovir disoproxil fumarate (TDF) has high antiretrovirus (ARV) activity and available in fixed dose combination (FDC). However, it has been found to cause renal dysfunction. Objectives: To document the prevalence, incidence, pattern of occurence and associated factors of nephrotoxicity in patients initiated on TDF based ART regimen in Mitchell's Plain CHC ARV Clinic and make recommendations. Methodology: The study was conducted by reviewing retrospective records of all ARV naïve HIV positive adults initiated on TDF based ARV regimen from January 2016 to June 2016. The creatinine clearance (CrCl) was calculated from follow up parameters till June 2018. Results: 87 patients were included in the study and 56% were female. The mean age was 34 years. Majority, 83%, had normal renal function at ART initiation. Older age [OR = 1.11; 95% CI (1.03–1.19), p =0.005], was associated with an increased probability of non-normal renal function at baseline. The incidence of CrCl < 90ml/min were 1.5% at 1 month post ARV initiation, 3.3% at 4 months, 6.1% at 12 months and 2.8% at 24 months while the prevalence were 10.5%,11.5%, 20.4% and 16.7% respectively. Older age and male gender were independently associated with prevalence of renal impairment. Conclusion: Renal dysfunction in patients initiated on TDF based regimen in this study varied and were relatively small when compared to the prevalence of renal dysfunction at initiation. Majority of the decline in CrCl were transient and patients were found to have recovered after further follow up. It is recommended that the frequency of renal function monitoring in patients on TDF regimen be done within programmatic guidelines based on patients' risk factors and potential poor outcomes.

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