A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree Master of Family Medicine, October 2013 / Botswana has one of the highest HIV prevalence rates in the world, with 32% of pregnant women and 24% of adults in the general population living with HIV. Although antiretroviral therapy (ART) or HIV/AIDS treatment is widely available in the public sector in Botswana, not all treatment-eligible patients utilise the services in a timely manner. The study aims to identify the factors associated with the intention of already screened HIV positive/AIDS patients, who met the government criteria, to enrol into the HIV treatment programme in Lobatse, Botswana. Methods: A Cross-sectional descriptive study was used, conducted at the Infectious Disease Control Clinic, Athlone Hospital, Lobatse over a 6-month period. A questionnaire was administered on systematically sampled participants, who met Botswana National antiretroviral treatment or HIV/AIDS treatment guidelines. Results: A total of 342 participants were enrolled, mostly female (67.3%) and single (50%). Majority of the participants were age 35-44 years (17%), attained up to primary level education (44%) and were mostly unemployed (54%). A majority (59%) intended to enroll into ART or HIV/AIDS treatment programme due to sickness, while others were motivated by voluntary testing and counseling (24%). The majority of the respondents received post-test counseling (97.3%) and most was motivated to seek ART or HIV/AIDS treatment (88.3%). Only (60%) disclosed their status to their relative. Although most participants (59.6%) were willing to be linked to care and support, most (65.1%) were ignorant of support groups and services available for them. Discussion: Although there is increasing access to ART or HIV/AIDS treatment, most participants still wait until they are sick or have symptoms before they enroll into ART. Supportive post-test counseling and conducive family environment were some of the enabling factors. Distance to health facilities and long queues are barriers to accessing care as well as stigma and discrimination. The most significant reasons for not continuing with the treatment were health facilities being far from place of residence and queuing for a long time to see a doctor and or collect medications. Conclusion: Sickness, public education, supportive family environment and effective post-test counseling were found to be significant motivators for intention to enroll into ART. Perceived barriers to accessing treatment include distance and time spent in the health facilities. Interventions are required to reduce stigma, bring health facilities nearer to the people, and increase efficiency in health facilities and increase access and utilization of the care and support groups.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Epidemiology in the field of Epidemiology & Biostatistics June, 2017 / Background: The burden of HIV infection is still high in South Africa. However, the use of ART has greatly improved treatment outcomes and survival. People infected with HIV and receiving ART are therefore living longer but with a likely increase in their cardiometabolic risk. Both HIV infection and anti-retroviral drugs have been shown to affect serum lipid levels and this may be among the reasons for the increased cardiometabolic risk in these subjects. The aim of this study was therefore to characterize the principal determinants of lipid levels in a large rural South African population with a high prevalence of HIV infection in which an array of factors that possibly modulate serum lipid levels had also been measured. Materials and methods: Data for this secondary analysis are drawn from a population-based cross-sectional study: the HAALSI/AWI-Gen collaborative study conducted in the Agincourt sub-district of the Mpumalanga province. 2110 adults 40+ years being monitored by the Agincourt health and socio-demographic surveillance system were randomly selected and recruited, after giving informed consent, between 2013-2016. Pretested questionnaires were used to collect personal, household, socio-demographic, behavioral, dietary, physical activity and self-reported health status. Anthropometric measurements were also conducted. Multivariable linear and logistic regression analyses were used to determine factors associated with serum lipid levels and dyslipidemia, respectively. Results: Results are presented for 2110 participants in this secondary analysis of which 60.3% were women with a mean population age of 58.54 ± 10.91 years. The HIV prevalence was 16.16% and did not differ substantially between men and women. Factors associated with total cholesterol level included age (unstandardized beta [95% CIs] was: 0.02 [0.01, 0.03]; p=0.014), male gender (-0.31 [-0.57, -0.05]; p=0.019), diabetes (0.31 [0.01, 0.61]; p=0.039), alcohol consumption (0.25 [0.02, 0.48]; p=0.038) and BMI (0.02 [0.01, 0.04]; p=0.030). Factors associated with triglycerides included age (0.01 [0.01, 0.03]; p=0.003), male gender (-0.09 [-0.19, 0.01]; p=0.053), diabetes (0.27 [0.13, 0.40]; p<0.0001), BMI (0.01 [0.01, 0.03]; p=0.044), hip circumference (-0.01 [-0.02, -0.01]; p=0.001) and waist circumference (0.01 [0.01, 0.02]; p<0.0001). Factors associated with HDL-C level included age (-0.01 [-0.01, 0.01]; p=0.055), male gender (-0.14 [-0.26, -0.02]; p=0.018), receiving ART (0.17 (0.04, 0.31); p=0.038), alcohol consumption (0.19 [0.07, 0.30]; p=0.002), waist circumference (-0.01 [-0.01, -0.001]; p=0.001) and visceral adipose tissue (-0.03 [-0.04, -0.01]; p=0.002). Age (0.02 (0.01, 0.03); p=0.005), male gender (-0.22 (-0.43, -0.01); p=0.044) and waist circumference (0.01 (0.01, 0.02); p<0.0001) were all associated with LDL-C levels. Being HIV+ and ART naive was associated with a higher risk of dyslipidemia (odds ratio [95% CIs] was 3.79 [1.27, 11.30]; p=0.032) compared to HIV negative participants. Other factors associated with dyslipidemia included being overweight (1.66 [1.20, 2.30] p=0.002) and obese (OR 1.85 [1.02, 3.35]; p=0.0004) and increased waist circumference (OR 1.02 [1.01, 1.03]; p<0.0001). Discussion and conclusion: We have demonstrated a high prevalence of HIV in an older population of rural South Africa, which mirrors the typical epidemiology of the epidemic in southern and eastern African regions. Our data suggest that HIV/ART status mainly influences HDL-C levels with ART use associated with higher HDL; and that untreated HIV infection can be linked to a greater risk of dyslipidemia. Dyslipidemia in the study population is driven by prevailing traditional cardiovascular risk factors such as obesity and diabetes. This data suggests that high ART coverage may reduce atherogenic risk and that lifestyle interventions to reduce the risk of obesity and diabetes are essential. / MT2017

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Pharmaceutical Affairs Johannesburg, 2012 / Objective: To determine the proportion of HIV+ patients who fail treatment on a yearly basis in a 5-year treatment cohort in Tshwane District Hospital and to determine the correlation of treatment failure with variables routinely measured at the clinic namely WHO stage, CD4 count, HIV viral load, age, gender, presence of concomitant diseases, concomitant medication and distance travelled to clinic. Design: A retrospective study with an analytical component was conducted using the hospital records of adult patients receiving antiretroviral therapy in 2004 and followed for 5 years (until 2009) at the Tshwane District Hospital. Methods: All adult patients receiving antiretroviral therapy in 2004 were identified and followed for the next 5 years till 2009 at Tshwane District Hospital. The proportion of patients that failed treatment yearly was calculated. Univariate analysis was used to compare all patients who failed at any time point with the patients who did not fail at all for all variables. A repeated measures logistic regression model was developed to determine the variables that impacted on the binary outcome, namely treatment failure or not. Results: Of the 1104 adult patients who were attending the TDH Immunology clinic in 2004, 870 adults were receiving ARVs. 333 patients (38.28 %) experienced treatment failure throughout the study period. 6.9 % (60/870) of the study population failed virologically. 307 of the 870 patients (35.29 %) failed treatment immunologically. 102 patients (11.72 %) experience treatment failure at the 12 month time point, 37 patients(4.49 %) at the 24 month time point, 57 patients(6.93 %) at 36 month time point, 101 patients(12.27 %) at the 48 month time point and 140 patients (7.01 %) failed treatment at 60 month time point. Univariate analysis showed significant correlation between treatment failure and non-adherer, interrupting treatment, defaulted treatment, viral load at baseline, 12, 24, 36, 48, 60 months, and CD4 count at baseline, 12, 24, 36, 48, 60 months. In the multivariate analysis, there was a significant association between short term stoppage of treatment (STSTOP) (coefficient ratio = 1.41; p<0.001), long term stoppage of treatment (LTSTOP) (coefficient ratio = 3.24; p<0.001), transfers from other health institutions (coefficient ratio = 1.96; p<0.001), regimen (coefficient ratio = -0.1734) and treatment failure. The change in log viral load at 12 months from baseline (LOGVLBL12) (coefficient ratio =-1.7145; p<0.001) was highly significant for reaching the end point - treatment v failure. Older patients were less likely to fail treatment (coefficient ratio = -0.0517, p<0.001) and patients with an advance stage of the disease (WHO stage 3 or 4) were at a lower risk of failing treatment (coefficient ratio = -0.4175; P=0.008). The CD4 count was significant in the univariate analysis P<0.01) and XTGEE (coefficient ratio =- 0.0001; p<0.001). There was no significant correlation between gender, place of residence, employment status and treatment failure. Conclusion: More than one–third of the patients receiving treatment in TDH failed treatment within the 5 year study period. The determinants of treatment failure are age, WHO stage, transfer from other institutions, short term stoppage of treatment, long term stoppage of treatment, CD4 cell count and the level of viral suppression within the first year of treatment (LOGVLBL-12). This study reinforces the need for identifying high risk patients earlier in treatment in order to implement strategies that might strengthen adherence to treatment.

A research report submitted to the Faculty of Medicine, University of the Witwatersrand, in partial fulfillment of the requirements for the Degree of Master of Medicine in the division of Plastic and Reconstructive Surgery. Johannesburg 2014 / With 67% of the world’s human immunodeficiency virus (HIV) infected population existing in Sub-Saharan Africa and recent access to highly active antiretroviral therapy (HAART); demand for plastic surgical intervention in addressing HIV-associated lipodystrophy has expanded dramatically. This study assessed the prevalence of lipodystrophy in a random clinic cohort, the demand for surgical correction, and risk of treatment non-compliance A questionnaire and database cross-sectional review of 554 patients was performed over a three-month period at the Themba Lethu Clinic, Johannesburg, South Africa. A total of 479 patients completed the questionnaire, 83% were female. Nearly 90% of patients were currently being treated, or had been treated with stavudine (d4T). The prevalence of lipodystrophy was 11.7%. Nearly 5.9% of patients had considered stopping treatment due to changes in body morphology following the onset of HAART, 47% of patients interviewed would consider surgery to correct unwanted physical changes following treatment with HAART. Male patients were satisfied by physical changes in their body habitus following treatment (pre-treatment satisfaction 38% vs. post-treatment satisfaction of 94%). Female patients had 6.5 times more breast hypertrophy related symptoms than in their pretreatment state. This study identified a prevalence of 11.7% of patients with HIV-associated lipodystrophy. A total of 3.8% of all patients would consider non-compliance on the basis of this side effect alone. The demand for surgical correction is significant, extends beyond patients diagnosed with HIV-associated lipodystrophy, and needs to be addressed.

M.Sc. (Epidemiology), Faculty of Health Sciences, University of the Witwatersrand, 2011 / Background and Objectives The advent of Highly Active Antiretroviral Therapy (HAART) has resulted in a significant reduction in HIV/AIDS related morbidity and mortality in sub-Saharan Africa. However, toxicities due to HAART continue to pose challenges to the success of different regimens. Severe hepatotoxicity is one of the significant adverse events occurring in patients on HAART. Information on the incidence and risk factors for severe hepatotoxicity in cohorts from resource poor settings is limited. It is against this background that we undertook the study to determine the incidence and explore factors associated with severe hepatotoxicity following HAART initiation in a South African cohort. Materials and Methods Secondary data analysis of a prospective cohort 9764 HIV-infected adult patients initiated on HAART at the Themba Lethu clinic antiretroviral rollout facility in Johannesburg, South Africa between 1st April 2004 and 30th June 2009 was conducted. Severe hepatotoxicity cases were identified within the first 12 months of initiating HAART as grade 3 or 4 elevation in baseline ALT levels. The incidence rate of severe hepatotoxicity was calculated and potential socio-demographic and clinical predictors were explored using Cox proportional hazard regression modelling. Results At baseline, 91.8% of patients were commenced on an efavirenz-based regimen while only 8.2% were on a nevirapine-based regimen. The median CD4 count at v initiation of HAART for this cohort was 80 cells/ mm3, a figure lower than the Department of Health (DoH) CD4 cut off for initiating HAART of 200 cells/ mm3. The overall incidence rate of severe hepatotoxicity was 10.7 (95% CI: 8.7 – 13.1) cases per 1000 p-yrs of follow-up. The period with the highest risk of severe hepatotoxicity was within 2 months of initiating HAART. Incidence of severe hepatotoxicity was 21.1(95% CI: 12.7 – 34.9) cases per 1000 p-yrs among patients on a nevirapine-based regimen and 9.7 (95% CI: 7.8 – 12.1) cases per 1000 p-yrs in those on an efavirenz-based one. The hazard for severe hepatotoxicity within the first year of initiating HAART was 2.17 times higher in individuals on a nevirapine-based regimen compared to those on an efavirenz-based regimen after adjusting for baseline ALT, baseline CD4, age and gender (HR = 2.17; 95%CI = 1.18 – 3.97; p = 0.013). Though imprecise, the estimate for baseline ALT category suggested an increased risk for severe hepatotoxicity in individuals with a baseline ALT more than 40 I.U/L compared to those with a baseline ALT of less than 40 I.U/L (HR = 1.63; 95%CI = 1.00 – 2.67; p = 0.050). Conclusion The results of the study suggest that severe hepatotoxicity following initiation of HAART in this cohort is low compared to other previously studied cohorts. The high incidence rate of severe hepatotoxicity in the first two months of initiating HAART necessitates the need for more frequent and careful monitoring of ALT levels early during therapy. Patients on a nevirapine-based regimen have a higher risk of developing severe hepatotoxicity when compared to their counterparts on an efavirenz-based regimen, a result consistent with findings from previous studies.

M. Pharm., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Background: According to the 2010 edition of the UNAIDS Report on the global AIDS epidemic, an estimated 320 000 (20%) fewer people died of AIDS-related causes in South Africa in 2009 than in 2004 due to the increase in availability of anti-retroviral medicines.(2) With this positive trend, the mindset should be shifted towards reducing adverse effects of ART. The need for permanent ART treatment and the significant increase in life expectancy have led to the observation of new, frequent, and sometimes severe drug-related adverse effects.(4) One of the most challenging and potentially dangerous side-effects is hyperlactataemia (Hlac) that may evolve to lactic acidosis (LA)(5) ART–associated Hlac may be asymptomatic, or symptomatic which in the extreme case can progress to life threatening acidosis. The latter, i.e. lactic acidosis is a fairly frequent and often misdiagnosed or under diagnosed and potentially fatal side effect of ARTs. (6) Objectives: To explore the relationship between Hlac/LA and gender, weight, dosage CD4 and regimen alterations in HIV patients on ARTs and to compare the earlier regimens to the revised regimens as independent risk factors for Hlac and LA. Sample size would be based on the hypothesis that newer regimens would reduce the incidence of Hlac and LA. Methods: A Retrospective study was conducted by reviewing 3 741 patient files from August 2004 to December 2007. This study was to assess the incidence and risk factors of Hlac/LA. Hlac was defined as a venous lactate measurement of ≥2.3mmol/L and LA was ≥5mmol/L. Immunological, virological, haemotological and biochemical results were recorded for all the patients. A second phase involved a Prospective study. Patients who were on treatment for >12 months were randomly selected from the queue at the clinic between the September 2008 and December 2009. Immunological, virological, haematological and biochemical information was recorded for all patients selected. Analysis involved descriptive statistics, comparison of means, frequency analysis and multivariate analysis. Results: Two-hundred and thirty two patients were identified with elevated lactate levels in the retrospective study. The incidence was 6.2% in this population, with gastro-intestinal symptoms, peripheral neuropathy, abdominal tenderness, rash and upper respiratory tract infection being the significant symptoms. The major risk factor was a low CD4 count. The prospective study included 292 patients with 24.3% with Hlac/LA with peripheral neuropathy (p 0.209), gastrointestinal symptoms (nausea, vomiting) (p 0.148) and abdominal tenderness (p 0.214) were the most significant symptoms. In terms of the hypothesis that newer regimens would lower the incidence of elevated lactate levels by 50%, the observed incidence of 24.3% is no different from previously reported rates. This therefore shows that although regimen changes have been implemented the overall incidence of Hlac appears to be unchanged but the LA rate was found to be significantly lower than before, 6.8 cases per 1000 patient years vs ±19 cases per 1000 person years.(16) Gastro-intestinal symptoms but not peripheral iv neuropathy; with low CD4 count, weight loss and low weight on entry were the significant risk factors, which is most likely representative of advanced disease. Conclusions: Although newer regimens have been introduced, Hlac/LA still exist. Healthworkers need to be on high alert for Hlac/LA particularly if a patient enters into the ART program with a low CD4 count and a low weight

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Masters of Public Health in the field of Health Measurement 22nd February, 2012 / Introduction: Barriers associated with good adherence to Antiretroviral Therapy (ART) among human immunodeficiency virus (HIV) infected adolescents are multiple and complex. Those barriers contribute to low adherence levels putting infected adolescents at risk of developing resistance and decreasing their survival time. Patients care givers psychosocial and demographic variables, medication related factors and health care delivering factors are among the barriers that correlate with non adherence to antiretroviral drugs (ART’s) among HIV infected adolescents. Those barriers vary across individuals within the same population of adolescents. This study was conducted to determine the level of adherence among HIV infected adolescents on ART and to identify barriers associated with non adherence among this population attending the Botswana Baylor Children’s Clinical Center of Excellence (COE) in Gaborone, Botswana. Materials and methods: A cross sectional analytical study using quantitative data was performed. A structured, self administrated questionnaire adapted from the AIDS Clinical Trials Group (ACTG) was used to identify the barriers while the socio-demographic and clinical data were retrieved from study participants’ medical records. The adherence level was estimated using the pharmacy pill count technique. The adolescents aged 13 to 18 years receiving ART for more than 6 months and attending the ART National Program at the time of the study and who did assent and had their care givers consent to participate in the study were included in the analysis. Results: A high adherence level (75.6%) was reported among the study participants. Besides gender, no other socio-demographic and clinical variables showed association with non adherence. Male adolescents were found to be 70% less likely to adhere to their medication than their counterpart females [p= 0.020, OR=0.30, 95% CI (0.10 – 0.85)]. Furthermore adolescents v who missed a dose because their pills were not collected from the pharmacy either by themselves or by their care givers were 77 % less likely to adhere to their ART medication than those who did not miss a dose because they had their medication collected [p= 0.019, OR= 0.23, 95%CI (0.064 – 0.837)]. Conclusion: A high proportion of HIV infected adolescents attending the Baylor Center of Excellence ART National Program were adherent to their medication. Despite the high level adherence to ART among this age group, interventions to improve adherence level should be designed with a focus on male adolescents and to reinforce counseling of care givers and adolescents about the hazards of poor adherence to treatment. Further research is however, needed to elucidate more about the two main barriers that were found to be significantly associated with non adherence among adolescents at Botswana Baylor Children’s Clinical Center of Excellence: male-gender and medication collection from the pharmacy.

After 25 years of existence, the Human Immuno-deficiency Virus (HIV) has become a global challenge. Yearly, about 3 million people in the sub Saharan region become infected with the disease each year, while 2 million die of the disease. The young, sexually active and those in the economically active group are mostly affected although other categories are also affected. Over the years efforts have been made to turn HIV infection from a death sentence to a manageable chronic disease through the use of antiretro viral treatment (ART). Despite the fact that this treatment is a life-long commitment with adherence being crucial to its effectiveness, some patients still default. This research study sought to identify the characteristics of HIV positive patients who are lost to follow up after the initiation of antiretroviral treatment over a 2-year period (2007-2008). A tick sheet was used to collect data from all the files of patients lost to follow up and 20 variables were tested. The conclusion reached is that age, sex, distance of residence to the ART site and economic capability contribute to ‘lost to follow-up’.

Orientador: Henrique Luiz Monteiro / Banca: Ismael Forte Freitas Júnior / Banca: Sandra Lia do Amaral / Resumo: Após a introdução da terapia anti-retroviral altamente ativa (TARV), houve significativo aumento da sobrevida e melhora da qualidade de vida de indivíduos portadores de HIV, porém, esses tratamentos têm efeitos colaterais que podem causar transtornos para seus usuários, dentre os quais, a lipodistrofia. Além de causar um novo estigma estético para os portadores do vírus a síndrome pode elevar o risco de doenças cardiovasculares e diabetes. Nesse contexto, torna-se importante dar atenção a estratégias de prevenção e tratamento da síndrome. A atividade física pode ser uma alternativa válida para este fim, no entanto existem poucos estudos que tratam dessa temática. Desse modo, o objetivo do presente estudo foi verificar a possível associação entre o nível de atividade física e a ocorrência de lipodistrofia relacionada ao uso de terapia anti-retroviral em indivíduos portadores de HIV. A casuística foi formada por 42 indivíduos portadores de HIV em uso de TARV, todos pacientes do Centro de Testagem e Aconselhamento da cidade de Presidente Prudente. O nível de atividade física foi obtido pela aplicação do questionário internacional de atividade física (IPAQ), enquanto a lipodistrofia foi diagnosticada pela técnica de auto-relato do paciente... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: After the introduction of the Highly Active Antiretroviral Therapy (HAART), there was significant increase in survival and improved quality of life among HIV-infected individuals, however, these treatments have side effects that may cause inconvenience to its users, among which lipodystrophy is. Besides causing a new aesthetic stigma for those with the virus, the syndrome may increase the risk of cardiovascular disease and diabetes. In this context, it becomes important to pay attention to strategies for prevention and treatment of the syndrome. Physical activity may be a valid alternative for this purpose, however there are few studies that address this issue. Thus, the purpose of this study was to investigate the possible association between level of physical activity and lipodystrophy occurence related to the use of antiretroviral therapy in HIV-infected individuals. The sample consisted of 42 HIV patients under antiretroviral therapy, all patients of the Center for Counseling and Testing in the city of Presidente Prudente. The level of physical activity was achieved by using the international physical activity questionnaire (IPAQ), whereas lipodystrophy was diagnosed by the technique of self-report of the patient... (Complete abstract click electronic access below) / Mestre

Thesis(MSc(Med)(Pharmacy))--University of Limpopo (Medunsa Campus), 2011. / High levels of adherence to ART are essential for maximal suppression of viral replication and avoidance of drug resistance. Pill counts are an indirect, objective method of assessing adherence. Patients can invalidate pill counts by manipulating the number of tablets returned. This paper describes a pilot study which investigated the ability of ‘mixed’ pill counts to detect deliberate masking of non-adherence to ART at a public sector ARV Clinic in Pretoria, South Africa. Seventy-eight adult patients on a first line regimen of ART were recruited. At the first return visit, a standard pill count was performed and adherence (% of tablets taken) was calculated. For the repeat prescription, three days’ extra supply was dispensed without the patients’ knowledge. At the second return visit, a ‘mixed’ pill count was performed and adherence was calculated. Patients were grouped into three categories based on calculated adherence: truthfully non-adherent (<100% adherence), adherent (100% adherence) and ‘over-compliant’ (>100% adherence, i.e. returning to the clinic with fewer tablets than required). Exploratory interviews were conducted with truthfully nonadherent and over-compliant patients to obtain explanations for discrepancies in pill counts. Twenty-nine (37%) patients completed the study. Reasons for drop-out or discontinuation from the study included the issue of prescriptions for 2-3 months’ ARV supply, missed appointments, regimen changes and failure to return remaining tablets to the clinic. Eleven patients (38%) were identified as over-compliant in one or more of the ARVs in their regimen. Nine of these patients agreed to be interviewed, of which three admitted to manipulating their tablet numbers. Reasons for manipulation included: being ’fine now’ and not in need of ARVs; changes in body shape; possibility of the social grant being terminated if non-adherent; getting a new supply and no need for remaining ARVs; knowing that the tablets would be counted for the study. This pilot study indicated that the ‘mixed’ pill count method is capable of detecting deliberate masking of non-adherence. Applying this method to a larger sample may better estimate the frequency of pill count manipulation by patients and help gain insight to reasons for this behaviour and the extent of actual non-adherence. Key words: dumping, manipulation, masking, over-compliance, HAART