Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.

Philosophiae Doctor - PhD / AIDS is considered a pandemic causing millions of deaths worldwide and a cure for this disease is still not available. Failure to implement early treatments due to the poor diagnostic methods and ineffective therapeutic regimens to treat HIV patients to achieve complete viral eradication from the human body has encouraged the escalation of this disease at an exponential rate. Though the current treatment regimens (High Active Antiretroviral Therapy) have aided in increasing the lifespan of HIV patients, it still suffers from some shortcomings such as adverse side effects and non-eradication of the virus. Thus, there is a need for a non-toxic therapeutic regimen to stop further infection of HIV-infected patients. Antimicrobial Peptides (AMPs) are naturally occurring peptides which are components of the first line of defence of many organisms against infections and have been proven to be promising therapeutic agents against HIV. The use of AMPs as anti-microbial agents is due to the fact that most AMPs have a net positive charge and are mostly hydrophobic molecules. These features allow AMPs to be site directed electro-statistically to the mostly negatively charged pathogens. In a previous study, a number of novel anti-HIV AMPs was identified using a predictive algorithm Profile Hidden Markov Models (HMMER). The AMP's threedimensional structures were predicted using an in-silico modelling tool I-TASSER and an insilico protein-peptide interaction study of the AMPs to HIV protein gp120 was performed using PatchDock. Five AMPs were identified to bind gp120, at the site where gp120 interacts with CD4 to prevent HIV invasion and HIV replication. Therefore, the aims of this research were to perform in-silico site-directed mutation on the parental anti-HIV AMPs to increase their binding affinity to the gp120 protein, validate the anti-HIV activity of these peptides and confirm the exclusivity of this activity by testing possible anti-bacterial and anti-cancer activities of the AMPs. Firstly, the five parental anti-HIV AMPs were used to generate mutated AMPs through insilico site-directed mutagenesis. The AMPs 3-D structures were determined using I-TASSER and the modelled AMPs were docked against the HIV protein gp120 using PatchDock. Secondly, an "in house" Lateral Flow Device (LFD) tool developed by our industrial partner, Medical Diagnostech (Pty) Ltd, was utilised to confirm the in-silico docking results. Furthermore, the ability of these AMPs to inhibit HIV-1 replication was demonstrated and additional biological activities of the peptides were shown on bacteria and cancer cell lines. In an effort to identify AMPs with increased binding affinity, the in-silico results showed that two mutated AMPs Molecule 1.1 and Molecule 8.1 bind gp120 with high affinity, at the point where gp120 bind with CD4. The molecular binding however showed that only Molecule 3 and Molecule 7 could prevent the interaction of gp120 protein and CD4 surface protein of human cells, in a competitive binding assay. Additionally, the testing of the anti-HIV activity of the AMPs showed that Molecule 7, Molecule 8 and Molecule 8.1 could inhibit HIV-1 NL4-3 with maximal effective concentration (EC₅₀) values of 37.5 μg/ml and 93.75 μg/ml respectively. The EC₅₀ of Molecule 8.1 was determined to be around 12.5 μg/ml. This result looks promising since 150 μg/ml of the AMPs could not achieve 80% toxicity of the human T cells, thus high Therapeutics Index (TI) might be obtained if 50% cytotoxic concentration (CC₅₀) is established. Further biological activity demonstrates that Molecule 3 and Molecule 7 inhibited P. aeruginosa completely after 24 hours treatment with peptide concentrations ranging from 0.5 mg/ml to 0.03125 mg/ml. Nevertheless, moderate inhibition was observed when CHO, HeLa, MCF-7 and HT-29 were treated with these peptides at peptides concentration of 100 μg/ml. The ability of these AMPs to block the entrance of HIV via the binding to CD4 of the host cells is a good concept since they pave the way for the design of anti-HIV peptide-based drugs Entry Inhibitors (FIs) or can be exploited in the production microbicide gels/films to suppress the propagation of the virus. / DST-NIC/Mintek

Master of Public Health - MPH / It is well documented that mortality rates have decreased and the survival of HIV and AIDS patients has been prolonged since the introduction of highly active antiretroviral therapy (HAART) in 1996. Although HAART has dramatically improved the prognosis of HIV disease, some HIV patients on HAART still die of HIV related illnesses. It is important to understand what these factors are in order to mitigate the impact on these factors on patient survival and achieve better outcome for these patients. The aim of this study was to determine risk factors for long term survival of patients on HAART in Uganda. Data for 2,244 out of 30,000 clients receiving care and treatment at TASO Entebbe was retrospectively analyzed. TASO Entebbe is a non-governmental HIV clinic that provides care and treatment to HIV positive clients. Long term survival in this case was defined as survival for more than 5 years after initiation on HAART. Logistic regression and survival analysis were conducted. Female clients had a 12% lower risk of death compared to the male clients (AHR=0.88 [CI: 0.443- 0.936]). Clients that had pulmonary TB had 1.3 times higher risk of death compared to clients that did not have pulmonary TB (AHR=1.33 [CI: 1.162-2.733]). Clients initiated at CD4 cell counts less than 250 cells/μl had almost 7 times higher adjusted odds of death compared to those initiated at CD4 cell counts greater than 500 cells/μl (AOR= 6.95 [CI: 2.882-16.744]) and clients initiated at CD4 cell counts between 250 cells/μl and 500 cells/μl almost 3 times higher adjusted odds of death compared to clients initiated at CD4 cell counts greater than 500 cells/μl (AOR 2.56 [CI: 1.004-6.520]). It is recommended that an aggressive HIV testing strategy be put in place to facilitate early identification of HIV positive patients. Early identification would enable early initiation into HAART well before the CD4 cell counts fall below 500 cells/μl. The observed higher risk of mortality amongst men suggests interventions to promote early HIV testing and treatment initiation amongst men. The observed high risk of mortality for patients with pulmonary TB, calls for aggressive TB case finding and treatment of positive in order to reduce the HIV/TB related mortality.

>Magister Scientiae - MSc / Adverse effects are a significant factor that determine how long patients will tolerate a given antiretroviral drug regimen. They also influence treatment options, and play an important role in the much needed adherence to treatment by patients on Highly Active Antiretroviral Therapy (HAART). This study is aimed at understanding adverse effects experienced by patients on the first line antiretroviral therapy at Keetmanshoop Hospital in Namibia. Methods : A retrospective quantitative method was used to review records of patients on first line antiretroviral treatment who started treatment between November 1st 2007 and December 1st, 2008 and followed up until they reached 36 – 48 months on treatment. Records of 94 patients were found eligible to be included in the study. Data was analysed using Stata 12 data analysis software. Results : The most reported adverse effect was musculoskeletal disorders (25%) whereas headache (16%) was the least reported. Low haemoglobin (78%) was the most common recorded hematologic adverse effect whereas low red cell distribution width and low mean platelet volume were the least recorded adverse effects (0%). A Male patient was more likely to experience a low haemoglobin levels compared to a female patient (adjusted OR: 3.29, 95% CI: 1.3 – 8.3). A male patient was found to be 64% times less likely to experience a higher mean cell haemoglobin compared to a female patient (adjusted OR. 0.31, 95% CI: 0.11 – 0.87). A patient on nevirapine was more likely to experience an elevated creatinine level compared to a patient on efavirenz (adjusted OR; 36.0, 95%CI: 2.02 – 62.5). At baseline, a patient who had prior exposure to ART had an 81 times (adjusted OR: 81.4, 95%CI: 5.3 – 119, p-value=0.00) increased odds of experiencing a high mean cell volume (MCV) compared to a patient with no ART exposure. A patient with a higher CD4 count was also less likely to experience a low hemoglobin compared to a patient with low CD4 count (adjusted OR; 0.31, 95% CI: 0.12 – 0.77). The author recommends further studies with higher sample size to confirm whether higher creatinine levels are more prevalent in patients on nevirapine compared to patients on efavirenz; this will have clinical implications especially in patients with impaired renal system. Antiretroviral treatment increases chances of developing macrocytosis anaemia; clinical implication of this condition may need to be investigated.

Magister Public Health - MPH / Background: The hallmark of HIV infection is immunosuppression which predisposes to unusual infections and malignancies generally known as opportunistic diseases (ODs). Globally, ODs are the major cause of morbidity and mortality in people living with HIV (PLHIV). Since the advent of Highly Active Antiretroviral Therapy (HAART), a significant decline in AIDS progression and ODs has been observed globally. However, most of the evidence suggesting sustained decline in AIDS progression and ODs has come from high-income settings with relatively less burden of ODs in the pre-HAART era. The findings of studies in high-income settings may not be generalizable to resource-limited settings. Lack of information regarding the burden of ODs in HAART-experienced populations in Nigeria and the risk factors for their occurrence has made it difficult to fully assess the sustained efficacy of HAART in the country. The aim of this study was to investigate the prevalence of and risk factors for HIV-related opportunistic diseases amongst HAART patients at the Federal Medical Centre (FMC) in Owerri, Nigeria. Study design and setting: A quantitative, cross-sectional descriptive and analytical study was conducted with 354 adult HIV-infected patients 15 years and above, who were on HAART for a minimum of 12 weeks at the HIV clinic of the FMC, Owerri, South-east Nigeria. Patients currently manifesting an OD whose onset ante-dated the commencement of HAART were excluded. The participants were recruited by simple random sampling. Data collection: Using a structured questionnaire, data was collected by clinicians through interviews, physical and laboratory examinations for patients that provided informed consent and met the study criteria. The questionnaire captured patient’s socio-demographic information and other relevant clinical/laboratory data. Data Analysis: The data was analysed using Epi info version 3.5.1 and Open Epi Version 2.2.1. Descriptive statistics for HIV-related ODs were carried out using percentages and frequencies tables for categorical variables and means (SD) or medians (IQR) for numerical variables. In univariate analysis, the Chi-square test was used to determine significance of association between OD and socio-demographic and clinical variables while the Student "t"-test was used to compare group means. Logistic regression model (multivariate analysis) was used to determine the independent risk factors for the occurrence of ODs using parameters that had a p-value of <0.25 on univariate analysis. All reported p-values <0.05 were considered statistically significant. Results: The mean age of the participants was 41.1 ± 10.0 years; and females were in the majority (65.8%). Over 40% of them were rural dwellers, 50.4% belonged to the lower socioeconomic class, and 55% had a monthly household income less than 20,000 Naira. Fifty percent (50%) of them had advanced immunosuppression at first presentation. The median duration of HAART (3 years) paralleled the median duration of HIV diagnosis (3.4 years) and HAART adherence rate was 78%. The overall prevalence of ODs was found to be 22.4%. Among the 76 patients diagnosed with ODs, the leading conditions were candidiasis (38.2%), TB (34.2%), dermatitis (25%), chronic diarrhoea (6.6%) and sepsis (6.6%). The independent risk factors for the occurrence of ODs were household income less than 20,000 Naira (Adjusted odds ratio [AOR] = 2.4, 95% CI 1.1-5.1), HIV duration of less than 3 years (AOR= 2.1, 95% CI 1.1- 4.2), advanced WHO clinical stage at baseline (AOR= 8.1, 95% CI 4.0-16.4), baseline haemoglobin less than 10 g/dl (AOR= 2.9, 95% CI 1.3-56.1), current CD4 cell count less than 200 cells/μl (AOR= 3.0, 95% CI 1.14-6.2), and HAART non-adherence (AOR= 5.4, 95% CI 2.6-11.2). Past history of TB was found to be a strong predictor of TB (AOR= 5.3, 95% CI 1.4-20.2). Conclusions: Opportunistic diseases are common in patients receiving HAART in Nigeria and candidiasis and TB remain the leading conditions. Late presentation and HAART non-adherence are among the strongest risk factors for ODs in patients receiving HAART. Others include duration of HIV diagnosis less than 3 years, presence of anaemia at the time of first presentation and having a low CD4 cell count while on HAART. Beyond these clinical risk factors, poverty increases the risk of developing an OD during HAART and may emerge a strong determinant of HIV-related ODs in developing countries. Recommendations: A high index of suspicion for ODs remains necessary in HAART patients. Health education on HIV screening and early presentation should be intensified. PLHIV who are anaemic before commencement of HAART, those with low CD4 cell count despite HAART use, and low-income earners should become target groups for a more aggressive evaluation for ODs. Prophylaxis for TB and fungal infections in the absence of active disease should be widely implemented in developing countries. HAART adherence should be intensified.

The introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in the mortality and morbidity associated with the acquired immunodeficiency syndrome (AIDS). Several problems are associated with HAART and include high costs of treatments, poor availability of drugs in low-income countries, poor compliance, severe adverse effects and drug resistance. Therefore, the focus of current research is the development of new antiretroviral drugs, improved treatment strategies and the discovery of new drugs derived from plants. Green tea (GT) and its active constituent epigallocatechin gallate (EGCg) have been found to be protective against cancer, cardiovascular and neurodegenerative diseases and were found also to have antimicrobial, antimalarial and more importantly antiviral activity. EGCg, in vitro has been shown to inhibit the human immunodeficiency virus (HIV) viral enzymes reverse transcriptase and protease, destroy viral particles and interfere with the attachment of gp120 to cellular receptor CD4. The aims of this study were firstly to investigate the in vitro antiretroviral activity of GT and EGCg on the LP-BM5 defective murine leukemia virus (MuLV) that induces a disease in C57BL/6 mice similar to AIDS in humans and secondly to investigate the effects of GT and EGCg on the in vitro cytotoxicity and antiretroviral activity of current antiretroviral drugs zidovudine (AZT), indinavir (IDV), hydroxyurea (HU) and chloroquine (CQ). To achieve the above aims an in vitro model that represents cell-to-cell spreading of the LP-BM5 MuLV was developed. Firstly the presence of the LP-BM5-defective virus in the BM5 cell line was confirmed using transmission electron microscopy (TEM) to identify viral particles, PCR and RT-PCR were used to determine the presence of viral DNA and RNA respectively and viral infectivity was confirmed in C57BL/10 mice. The cytotoxicity of each drug and combination was evaluated with the MTT assay in the SC-1 cell line, the predominant cell type in the in vitro cell culture model. GT was the least cytotoxic, followed by AZT, IDV, EGCg, HU and CQ. Co-cultures (BM5:SC-1, 1:10000) that represented cell-to-cell transmission of the virus were established. Real time PCR for proviral DNA revealed that IDV, AZT and HU completely suppressed, CQ dose dependently reduced while GT and EGCg had no effect on viral transmission. Findings using AZT and IDV thus validated the use of this in vitro co-culture model for first line screening of new drugs and plant extracts. The effect of GT or EGCg in combination with AZT, IDV, HU or CQ was also evaluated as GT or EGCg could enhance the antiretroviral effects or decrease cellular toxicity of these drugs. For GT with AZT a mix of synergism and antagonism on cell toxicity was observed with little to no effect on the antiretroviral activity of AZT. Antagonism on cell toxicity was observed for GT with IDV, with no effect on the antiretroviral activity of IDV. In contrast EGCg significantly reduced the antiretroviral activity of IDV. A strong antagonistic effect was observed for GT with HU, with GT reducing the antiretroviral effect of HU. For combinations of AZT with EGCg and HU with EGCg a similar effect was observed as for AZT and HU respectively combined with GT. Synergism in cytotoxicity was observed between GT and CQ associated with a significant decrease in viral loads while EGCg combined with CQ had an opposite effect at higher concentrations. In conclusion, the in vitro co-culture model of BM5 and SC-1 cells was successfully used to evaluate combinations of GT and EGCg with AZT, IDV, HU and CQ. Interesting and often contradicting effects were observed, such as seen for IDV in combination with GT and EGCg as well as CQ in combination with GT and EGCg. These effects may be of clinical relevance and further investigation is warranted. / Dissertation (MSc)--University of Pretoria, 2009. / Anatomy / unrestricted

Due to the increasing availability of ART (antiretroviral therapy),HIV is starting to be seen as a chronic disease. This has several effects on families, one of which is the need to disclose their HIV status to children who were born with the illness. Potential barriers and available support structures with regards to paediatric HIV disclosure need to be considered before specific guidelines can be given to caretakers and health care providers. This study aimed to explore and describe the patterns of paediatric HIV disclosure or non-disclosure using a sample of caretakers or parents of children/adolescents who were born with HIV. The Disclosure Decision Making Model (DDMM) was used as a framework to understand the decision-making process that leads to either disclosure or non-disclosure. Qualitative data was gathered by means of in-depth, semi-structured interviews, conducted in English. Ten participants were recruited from a community health care centre that offers HIV counselling and testing in the Nelson Mandela Bay Health District. Data gathered was transcribed and analysed using thematic analysis. Lincoln and Guba’s model was used to determine the trustworthiness of the data. The two themes that emerged from the study were (1) caretakers wish to disclose HIV status to the child but identified barriers to doing this and, (2) caretakers identified factors that helped them to disclose the child’s status. This study provides a more in-depth understanding of the factors that influence disclosure in a resource-limited setting in the Eastern Cape.

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