Thesis (M.CUR.) --University of Limpopo, 2014. / Background: The national HAART programme in South Africa was launched in April 2004. Highly Active Antiretroviral Therapy (HAART) is the medication that slows down the progression from HIV to AIDS, while it had been introduced in Western countries in 1996. Adherence to ART is the major factor in ensuring the virologic success of an initial regimen and is a significant determinant of survival for HIV-infected patients with the wild type virus who are on highly active antiretroviral treatment. Patients with suboptimal adherence are at risk, not only of HIV progression but also of the development of drug resistance and consequent narrowing of options for future treatment. Sub-Saharan Africa carries the highest burden of HIV infections and HIV / AIDS related mortality in the world. South Africa is reported to have the largest population living with the HIV infection. Aims: The aim of the study was to explore factors that contributed to non- adherence of patients to HAART at the Kanyamazane Clinic, Ehlanzeni District, Mpumalanga Province. Study method: A qualitative, exploratory, descriptive, and contextual research design was used for this study. A non-probability purposive sampling method was used to select participants ranging from 15 to 60 years of age and who were on HAART for more than one year. Fifteen participants were selected and the sample size was determined by data saturation. Semi-structured interviews were conducted to collect data through the use of an interview guide on their structured follow-up dates and audio recordings of the interviews were made. Data was analysed following the Tesch’s method. Themes and sub-themes were developed. Results: Findings indicate that factors contributing to non-adherence of patients to HAART are the patient-provider relationship and delivery of services, waiting hours and overcrowding, working hours of the facility, forgetfulness and experiencing better health, belief systems, side-effects, pill burden, migration due to employment, poverty and unemployment, as well as disclosure, stigma, and discrimination. Conclusion and recommendations: The study recommends that HAART services should be provided every day, including on weekends, to improve access and to reduce waiting times; and economic empowerment through skills acquisition programmes to participants and provision of jobs to earn a living. Keywords: Non-adherence, highly active antiretroviral treatment, regimen, drug resistance.

Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence predict response to HAART as measured by CD4 count, weight gain and functional status in a cohort of patients in Roma, the Kingdom of Lesotho. Method: Data were collected from a computerised database of the Antiretroviral Centre of the hospital. A cohort of 300 subjects was identified from hospital records from January 2007. Each of these subjects was followed up over a period of 12 months with data obtained for at least two visits within the 12-month span. Data were obtained on weight and CD4 at baseline, three months and also at six and 12 months, and data for haemoglobin were obtained only at 12 months. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints, as well as for each endpoint separately. Results: Three-hundred patient records were analysed. Approximately 70% of the patients had a CD4 increase of at least 150 cells over baseline values at the end of the review period and in 52.3% of the patients an increase in weight of 10% over baseline measurements was seen. Seventy-nine patients (26.3%) had a haemoglobin level of at least 14g/dL at 12 months, regardless of baseline values or gender. The inclusion of Zidovudine (AZT) in treatment regimens was found in 73% of the patients and in multivariate analysis AZT was associated with not having anaemia at the end of the review period. However there was a slight reduction in haemoglobin level in the first two to three months of therapy in comparison with both Stavudine (d4T) and Tenofovir (TDF) but not significant enough to result in clinical anaemia. Baseline CD4 values were similar for all treatments options but dissimilar in other outcome variables and continued to vary significantly throughout the review period. The outcomes of multivariate analyses suggest that the male gender appears to have better response to HAART as seen in each of the multivariate models. The most important determinant of haemoglobin response was baseline haemoglobin values. In the haemoglobin-associated multivariate model, HAART is associated with an increase in haemoglobin over baseline values. A history of TB prior to HAART was a major factor in weight response and it is thought to be as a result of IRIS, which is the unmasking of latent infections as the immune system reconstitutes. CD4 values have no direct influence on weight however, but an increase in weight was observed in all therapy groups. Conclusion: Clinical and immunological parameters can be used to monitor response to HAART and predict treatment outcomes. These parameters can be organised into monitoring tools that will be useful in resource-limited areas. This study suggests that AZT-containing regimens appear not to result in anaemia and that symptomatic anaemia might need additional investigation. Treatment with TDF appeared to have shown the best possible response pattern more but patients on TDF therapy will have to be included in the study to justify this observation. / Dissertation (MSc)--University of Pretoria, 2012. / Clinical Epidemiology / unrestricted

Objective: This study aimed to evaluate the association between the intensity of menopausal symptoms and highly active antiretroviral therapy (HAART) adherence in middle-aged women with human immunodeficiency virus (HIV) infection. Methods: In this cross-sectional study, 313 Peruvian women with HIV infection (age 40-59 years) were surveyed and classified as adherent or non-adherent to HAART based on the Antiretroviral Treatment Adherence Evaluation Questionnaire. The intensity of menopausal symptoms was assessed with the Menopause Rating Scale, and categorized as none, mild, moderate, and/or severe. Age, sexual orientation, used HAART scheme, time since HIV diagnosis, menopausal status, risk of depression, and presence of comorbidities were also assessed. Poisson generalized linear models with robust variance were performed in order to estimate crude prevalence ratios (PRs) and adjusted PRs using statistical (a1PR) and epidemiological criteria (a2PR). Results: A total of 19.9%, 32.6%, and 15.0% of all women presented mild, moderate, and severe menopausal symptoms, respectively. Overall, 70.6% women were non-adherent to HAART. The probability of non-adherence was higher in women with mild, moderate, and severe symptoms as compared to asymptomatic women in the non-adjusted model (PR: 1.79, 95% confidence interval [CI]: 1.39–2.29; PR: 1.76, 95% CI: 1.38–2.23; and PR: 2.07, 95% CI: 1.64–2.61, respectively) and the adjusted model. Conclusion: The severity of menopausal symptoms was associated with HAART non-adherence in HIV-infected middle-aged women. / Revisión por pares

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 Physiotherapy. Johannesburg, 2015 / The Human Immunodeficiency Virus (HIV) has been found to cause muscle weakness, wasting and peripheral neuropathies. The specific relationship between lower limb muscle strength and lower limb function in HIV positive patients on Highly Active Antiretroviral Therapy (HAART) has not been examined. The aims of the current study were to establish lower limb muscle strength in HIV positive patients on HAART, establish lower limb muscle strength in HIV negative people, compare lower limb muscle strength between patients who are HIV positive on HAART and HIV negative people, establish lower limb function in patients who are HIV positive on HAART and to establish the relationship between lower limb muscle strength and lower limb function in patients who are HIV positive on HAART. A cross-sectional, descriptive study design was used. Dynamometry was used to measure lower limb muscle strength. The lower Extremity Functional Scale (LEFS) was used to determine lower limb function. A pilot study was done to establish the feasibility and proficiency required to perform hand held dynamometry. Intra and inter-rater reliability were also determined during the pilot phase. Intra and inter-rater reliability were high for the raters' measurement of lower limb muscle strength using a dynamometer with 'r' values of 0.97. For HIV positive patients on HAART, 19% (n=22) were in the age band 45-49years, whereas 33% (n=10) of HIV negative subjects were in age interval 25-29 years. Those over 45 years who were HIV positive on HAART constituted 57% (n=64) of the sample. The mean muscle strength obtained ranged from 9.30kg/m2 in ankle dorsiflexors to 15.80kg/m2 in hip extensors in HIV positive people on HAART for an average of 4 years while knee flexors generated 11.81 kg/m2 and knee extensors generated 15.36kg/m2 in this cohort.Jn the HIV negative matched group, the mean muscle strength ranged from 11.20 kg/m2 in ankle dorsiflexors to 17.70 kg/m2 in hip extensors while knee flexors generated 12.65kg/m2 and knee extensors generated 17.07kg/m2. The majority 78% (n=88) of HIV positive patients on HAART had no difficulty with lower limb function while 22% (n=17) had difficulty. Only 2% (n=2) of HIV positive patients on HAART had quite a bit of difficulty with lower limb functional activities after measurements using the Lower Extremity Functional scale (LEFS). A multiple linear regression showed that there was a positive correlation coefficient of r=0.71 (p-value= 0.00) between lower limb muscle strength and lower limb function. The coefficient of determination 0.50 means that 50% of the changes in lower limb function are attributable to lower limb muscle strength. Gender, employment status and mode of transport also positively affected lower limb function. A detailed regression model showed that lower limb ankle plantar flexors contributed the most to lower limb function in this cohort. This is contrary to International literature which states that hip and trunk muscles are the most active in HIV negative people during lower limb functional activities. That plantar flexors contribute the most in lower limb functional activities instead of hip and trunk muscles confirms the existence of proximal weakness in this cohort which was established by other researchers. This study highlighted that 50% of lower limb function is a result of lower limb muscle strength in HIV positive people on HAART attending an outpatient clinic in Mutare, Zimbabwe. Ankle plantar flexors instead of hip flexors were the most active muscle group in lower limb functional activities in this cohort. It therefore means exercise prescription to activate/strengthen hip flexors and other proximal muscles will improve this population's lower limb functional activities since progressive resisted aerobic exercises have been proved to strengthen muscles. / AC2016

Original published work submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctorate of Philosophy in Virology. Johannesburg 2017. / Introduction: HIV-infected and HIV-exposed-uninfected children have a heightened susceptibility to some vaccine preventable disease. There is a paucity of data on immunogenicity of vaccines in these children, including HIV-infected children who are initiated on early antiretroviral therapy (ART). We evaluated the effect of maternal HIV-exposure and timing of ART in HIV-infected children on antibody responses to combined diphtheria-toxoid (DT) -tetanus-toxoid (TT)-whole cell pertussis (wP) and Haemophilus influenzae type b conjugate vaccine (HibCV); monovalent hepatitis B vaccine (HepB) and live-attenuated measles vaccine (MV). Methods: Samples obtained from children aged 6–12 weeks who had been enrolled into the CIPRA-SA study were analysed. Briefly, HIV-uninfected children born to HIV-uninfected (HIV-unexposed) and HIV-infected mothers (HEU). Additionally, we enrolled perinatally HIV-infected children with CD4+%≥25% randomized to deferred-ART (i.e. initiated when clinically or immunologically indicated per the then WHO recommended treatment criteria; ART-Def) or immediate-ART initiation (i.e. initiated on ART immediately upon confirmation of HIV-infection status at 4-10 weeks of age; ART-Immed). Children enrolled in the ART-Immed arm were further randomized to interrupt ART at one-year (ART/12m) or two-years of age (ART/24m). Additionally, a convenience sample of HIV-infected children with CD4+<25% initiated on immediate-ART was enrolled (ART-CD4+<25%). Children received a primary series of DTwP-HibCV/HepB at 6, 10 and 14 weeks of age; and MV at 40 weeks of age. Booster dose of DTwP and MV was given at 15-18 months of age. Sampling time-points were: prior to the first dose of vaccine, four weeks after the third dose (18 weeks age), 24 weeks after the third dose (39.3 weeks of age), at the time of the booster dose (15- 18 months age), two to four weeks after the booster dose and at 24 months of age. Samples were analysed for antibodies for DT, TT, PT, FHA, HepB measured by Luminex microbead-immunoassay; and MV antibodies were quantified by an indirect enzyme immunoassay. Results: Antibody kinetics and response to primary series of DTwP-HibCV/HepB: Pre-vaccination GMCs were higher in HIV-unexposed than HEU children for TT, but lower for HepB, DT and FHA. Post-vaccination, sero-conversion, sero-protection and GMCs were similar in HEU and HIV-unexposed children for all vaccines. Furthermore, GMCs were higher in HIV-unexposed for TT, DT, HepB and FHA than in ART-Immed children; and for TT, HepB and PT than in ART-Def children. Nevertheless, there was no difference in proportion of HIV-unexposed and HIV-infected children who developed sero-protective vaccine-specific antibody levels post-vaccination. The timing of ART initiation generally did not affect immune responses to vaccines between HIV-infected groups. Antibody kinetics and booster responses to DTwP-HibCV/HepB vaccines: Pre-booster GMCs were generally higher in HIV-unexposed than HIV-infected children for all vaccine epitopes. Post-booster and at 24 months of age the ART-Def group had lower GMCs (except to FHA), and were less likely to have sero-protective antibody levels compared to HIV-unexposed group. Also, post-booster and at 24 months of age, GMC were generally higher in HIV-unexposed than ART-Immed children, and a higher percentage of HIV-unexposed than ART-Immed children maintained antibody levels ≥1IU/ml to TT and DT at 24 months of age. The GMCs and percentage of children with sero-protective thresholds were similar pre-booster and at 24 months of age between HIV-unexposed and HEU children. Antibody kinetics and response to measles virus vaccine: At 7.3 weeks of age, the proportion with sero-protective titers was higher in HIV-unexposed (65.2%) compared to any HIV-infected group (range: 16.7% to 41.8%); but dropped to <17% in all Groups at age 19.6 weeks. Twenty-eight weeks following the first measles-vaccine, ART/12m were less likely to have sero-protective titers (79.3%) compared to HIV-unexposed (94.8%; p<0.001), ART-Def (95.7%; p=0.003) or ART/24m (92.1%; p=0.02). Although the proportion with sero-protective levels were similar between groups immediately post-booster dose, this was lower in HEU (79.6%; p=0.002) and ART/12m (80.3%; p=0.01) compared to HIV-unexposed (94.3%) 41-weeks later. Conclusion: Primary vaccination with DTwP-HibCV/HBV of HIV-infected children initiated on early-ART confers similar immunity compared to HIV-unexposed children. HIV-infected children had poor anamnestic responses, if ART was not initiated prior to primary vaccination. In contrast, the memory response and persistence of antibody to most vaccine epitopes were similar between HIV-unexposed and HEU children. Increased waning of vaccine induced immunity over a 24 month period in ART-Def, ART/12m and HEU children following MV booster-dose; indicating the need for further booster doses after two-years of age in these children. I recommend close monitoring of HEU children, as this group makes up most children born to HIV-infected mothers and what facets of the immune system have been impacted by maternal exposure to HIV. / MT2017

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Few studies have assessed the optimum second line highly active anti-retroviral therapy (HAART) regimen in patients who had failed on the first-line HAART in resource-limited settings. This study aimed to compare the Protease inhibitor (PI)-based second line HAART regimens used in one clinic in Trinidad by comparing immunological, virological and clinical outcomes of patients on the different second line HAART regimens. The records of 35 treatment-experienced patients, over 21years of age and on PI-based regimens for at least six months, were analysed using SPSS version 20. The regimen containing TDF/FTC/AZT/LPV/r proved to produce superior outcomes compared to the other second line regimens. Due the small number of usable patients’ records, the findings cannot be generalised but indicate directions for future studies attempting to compare the treatment outcomes of different second line HAART regimens / Health Studies / M. A. (Public Health)

Immunologic monitoring is part of the standard care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunologic monitoring in Ethiopia. This study assessed the pattern of immunologic monitoring, immunologic response, level of immunologic treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. A total of 1,321 documents of patients reviewed revealed timely immunologic monitoring were inadequate. Despite overall adequate immunologic response, the prevalence of immunologic failure was 11.5% (n=147). Having WHO Stage III/IV of the disease and a higher CD4 (cluster differentiation 4) cell count at baseline were identified as risks for immunologic failure. These findings highlight the magnitude of the problem of immunologic failure. Prioritizing monitoring for high risk patients may help in effective utilisation of meager resources / Health Studies / M.A. (Public Health)

Immunologic monitoring is part of the standard care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunologic monitoring in Ethiopia. This study assessed the pattern of immunologic monitoring, immunologic response, level of immunologic treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. A total of 1,321 documents of patients reviewed revealed timely immunologic monitoring were inadequate. Despite overall adequate immunologic response, the prevalence of immunologic failure was 11.5% (n=147). Having WHO Stage III/IV of the disease and a higher CD4 (cluster differentiation 4) cell count at baseline were identified as risks for immunologic failure. These findings highlight the magnitude of the problem of immunologic failure. Prioritizing monitoring for high risk patients may help in effective utilisation of meager resources / Health Studies / M. A. (Public Health)