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Item Structural and enzymatic studies of HIV-1 subtype C protease(2019) Shabangu, BonginkosiHuman immunodeficiency virus (HIV) is a retrovirus that infects T-lymphocytes in the human immune system causing a condition known as Acquired Immunodeficiency Syndrome (AIDS). At the moment, there is an estimated 1.2 million people dying annually from diseases related to AIDS and ~ 36.7 million people are currently infected with HIV across the globe. There are 10 subtypes found within the major group of HIV-1 and subtype C overwhelmingly drives the South African epidemic and accounts for more than 50% of the world infections. The continuous infection and maturation of HIV-1 is yielded by the three viral enzymes; namely, reverse transcriptase, integrase and protease. HIV-1 relies on the catalytic efficacy of the protease enzyme for cleaving precursor polyproteins to yield structural and functional proteins. When HIV-1 protease is inactivated, either by an inhibitor or mutagenically, the virion will remain non-infectious. Thus, the HIV-1 protease is an opportune drug target. It is an important variant in the study of the pathogenesis, treatment and prevention of HIV-1 infections. The study intended to characterise and evaluate the catalytic activity of HIV-1 South African subtype C protease which exhibits high variability compared to subtype B protease. For characterisation properties, far-UV circular dichroism, intrinsic fluorescence spectroscopy and size exclusion high-performance liquid chromatography were used to evaluate secondary, tertiary and quaternary structure, respectively. Secondary structure results indicated a trough at 216 nm which means the protein is predominantly β-sheeted. Using intrinsic tryptophan as a probe, the tertiary structure of protease revealed that the local structural environment had not been perturbed and it was indicated by fluorescence emission intensity peak at 355 nm. The results of the size exclusion-high performance liquid chromatography study revealed that the dimeric molecular size of the wild-type protease was 22 kDa. The proteolytic efficiency of the subtype C wild-type protease was evaluated following the hydrolysis of a fluorogenic substrate resembling the CA/p2 cleavage site in the gag-pol polyprotein precursors. The KM was determined as 42.07 μM, Vmax was 0.047 μmol.min-1, specific activity was 76.46 μmol/min/mg, kcat was 24.02 s-1 and kcat/KM was 0.084 s-1μM-1. In the presence of darunavir, the Ki value for protease was determined as 3.4 nM, for saquinavir it was 6.2 nM and for ritonavir it was 9.4 nM. The protease inhibitor GRD 110D had a Ki of 27 nM, showing high susceptibility compared to the other three FDA-approved HIV protease inhibitors (PIs). A molecular docking study was carried out to analyse and compare the binding mode of the FDA-approved HIV PIs. The docking results indicated that the protease recognition site is hydrophobic due to the two-flexible glycine-dense β-sheets and that subtype C protease (PDB code: 3U71) polymorphisms result in an altered flap-hinge region, thus making it less susceptible to inhibitors as compared to subtype B protease (PDB code: 2P3B). The results of the comparative binding mode analysis of all the FDA-approved drugs could be useful for the design of new potent inhibitors of HIV-1 protease.Item Anti-gp120 and anti-p24 aptamers: potential for use as flow cytometry reagents(2018) Malatji, Kanyane BridgettIntroduction: Aptamers are nucleic acids selected by systematic evolution of ligands by exponential enrichment (SELEX). They have potential as alternatives to antibodies in research and diagnosis. Their main advantages over antibodies are that they are nonimmunogenic and relatively inexpensive to produce. The aim of this study was to generate fluorescein isothiocyanate (FITC) conjugated gp120 aptamers as well as synthesize p24 aptamers and to potentially use them for detecting human immunodeficiency virus (HIV-1) infected cells. Methods: The gp120 aptamer was conjugated with FITC by incubation with 1-Ethyl-3(3-dimethylaminopropyl)carbodiimide (EDAC) and imidazole. The conjugation and binding to the glycoprotein was confirmed using flow cytometry and capture assay. Aptamers against p24 were selected using SELEX and their sequences elucidated by next generation sequencing. Results: The conjugation of the gp120 aptamer with FITC increased fluorescence emission 24 -fold from baseline. Similar data were obtained when beads coupled with HIV-1 gp120 or whole viruses were detected with the FITC-conjugated aptamer by flow cytometry and capture assay, respectively. When compared to a commercially available antibody (biotinylated anti-gp120 polyclonal antibody), the FITC-conjugated aptamer showed better emission of fluorescence. During the synthesis of p24 aptamers an enrichment of binding sequences was observed. Furthermore, 90,500 sequences were identified by deep sequencing out of the initial 1014 ss-DNA library. Conclusion: A FITC-conjugated gp120 aptamer that can bind the glycoprotein on coated beads or on a whole viral particle was generated. The aptamer is a potential low cost reagent for use in HIV/AIDS research or diagnosis. Furthermore, the selection of p24 aptamers was performed and sequences that bind the target were identifiedItem Factors associated with World Health Organisation (WHO) clinical staging and related characteristics in HIV positive patients: an application of multistate, missing data and modelling techniques(2019) Batsirai, MurapaBackground Human Immunodeficiency Virus (HIV) remains a significant problem in sub-Saharan Africa which has the highest number (25.6 million) of people living with HIV (PLHIV). South Africa is amongst the top rank of sub-Saharan Africa countries with the highest HIV prevalence. Many studies have been done to have an in-depth understanding of HIVandAIDSdiseaseresultinginvariousinterventionsbeingimplementedtoimprove the lives of people infected by the disease. These studies are usually done using longitudinaldesignswhichhavetheadvantageofenablingresearcherstoobservepatient changes (outcomes) over time; however, they are prone to missingness due to unobserved data as patients may miss scheduled visits. This study aims to determine transition probabilities between WHO stages I, II, III and IV over time and compare Rubin’s and Bayesian methods in determine factors associated with WHO stage ailments and symptomatic conditions amongst HIV infected patients on patient level data from the Adult Wellness study. Methods The researcher conducted a secondary data analysis of the Adult Wellness study which was conducted from 2002 to 2010, to be able to quantify changes in ailments and symptomatic conditions over time, the researcher fitted the general multi-state Markov model which assumes that patients may develop more severe ailments and symptomaticconditions. ThestatesweredefinedbasedonWHOstages,thatis,stage I, II ,III and IV. The researcher also fitted three random effects ordered logistic regression models to determine factors associated with these WHO stage outcomes. The researcher employed the maximum likelihood estimation (MLE) on the first model fittedonrawdataandsecondmodelaftermultipleimputation(MI)toaccountformissing data. The last model adopted Bayesian estimation (BE) to the raw data. Finally, the researcherperformedasensitivityanalysisusingsimulateddataandfittedallthethree models described earlier. Results A total of 2,609 patients accounted for 12,102 observations were analysed. Majority of the patients were females (77.4%) antiretroviral therapy ART naïve (61.5%) having attained Grade 0-12 (77.9%). The Markov multi-state model showed that patients in WHO stage II were 1.33 times more likely to move to WHO stage III than WHO stage I whilst patients in WHO stage III were 2.26 times (0.16118/0.07124) more likely to move to WHO stage II than progressing to WHO stage IV. The probability of remaining in WHO stage I was 59% after eight year follow up period. Relative to patients with no ailments and symptomatic conditions, patients with one HIV ailments or symptomatic condition has an INCREASED RISK of progressing to advanced WHO stages, (model with raw data OR 2.07, 95%CI: 1.23-3.30). There were some unexpected results were patients on ART and cotrimoxazole (CTX) drugs showed to have increased odds of becoming worse than their counterparts. This was evident in all the three models: raw data MLE model OR 1.5828 (95% CI 1.1948,2.0969) and OR 2.0670 (1.5619,2.7355); MI MLE model OR 1.2252 (95% CI 1.0884,1.3793) and OR 1.5438 (95% CI 1.3186,1.8074); and raw data BE model OR 1.6096 (95% CI 1.2055,2.0952) and OR 2.0758 (1.5507,2.7270) for ART and CTX respectively. Both MLE and BE for the raw data gave similar estimates; however, these estimates were different from the MI MLE model which were more precise (smaller standard errors). Conclusions The results showed that patients had an increased chance of remaining in the same state than either advancing in WHO stages of ailments and symptomatic conditions or recovering. If the level of missing data is reasonable, it is recommended to apply the MI techniques. Multiple imputations and Bayesian missing data methods should be used together and determine which one produce better results per each situation. Finally simulated results showed that multiple imputation and Bayesian models become different as the percentage of missing data increasesItem Defining the role of FC effector function in natural HIV-1 infection(2018)Human immunodeficiency virus type 1 (HIV-1) infects 2 million individuals annually, highlighting the need for an effective vaccine. While broadly neutralizing antibodies (bNAbs), naturally elicited in some HIV-infected individuals, can prevent infection in animal models these have not yet been stimulated by vaccination. RV144, the only HIV vaccine to show any efficacy, implicated the antibody Fc region in protection through functions such as antibody dependent cellular cytotoxicity (ADCC), cellular phagocytosis (ADCP) and complement deposition (ADCD). Consequently, we aimed to characterize Fc effector functions in the context of a bNAb response to inform vaccine design and improve antibodies for passive immunization. This thesis describes the development of a novel assay to measure antibody dependent cellular trogocytosis (ADCT) in HIV infection for the first time. ADCT results in rapid cell death of target cells through the removal of membrane fragments, which is distinct from ADCP. Individuals that developed bNAbs showed higher levels of ADCT and further investigation using assays measuring ADCP, ADCC and ADCD revealed they developed a diversified and potent Fc response early in infection that clearly separated them from other HIV-infected individuals. This profile correlated with good germinal center activity and increased subclass diversity, demonstrating a common mechanistic link between the regulation of the Fc and Fab mediated activities. An individual with bNAbs, CAP256, who also developed potent Fc effector function was found to have persistently high levels of IgG3 which is the most polyfunctional IgG subclass. Monoclonal antibodies isolated from this donor revealed natural usage of a novel IgG3 allele that showed both improved Fc effector function and neutralization compared to IgG1 versions. Hinge switch variants revealed that the increased IgG3 hinge length was responsible for improved neutralization. Our data describe common immune determinants associated with both Fab and Fc function as well as a new Fc effector function, ADCT. This highlights how cooperation between the variable and constant regions, facilitated by the hinge region, could be exploited to enhance the functionality of antiviral antibodies for passive immunity. Overall, these studies provide further clarity on the role of Fc effector functions in HIV infection.Item Exploring postgraduate University students' perceptions regarding the role of culture in the transmission, prevention and treatment of HIV and AIDS in Gauteng(2018) Chimonyo, Tapiwa CrystalThe regression in the spread and prevalence of HIV and AIDS epidemic over the years, especially on young people, has been an issue of utmost importance globally. A significant amount of resources, both human and financial, have been channelled into the development of strategies on how prevention and treatment of HIV and AIDS can become more effective. Within the sub-Saharan Africa region, South Africa included, HIV and AIDS among young people have also been a cause for concern. Studies have identified a number of factors that are believed to affect the effectiveness of these strategies, and these include, among others, poverty, low levels of education and culture. The reduced effectiveness of some HIV and AIDS transmission, prevention and treatment strategies are attributed to a number of cultural norms, beliefs and practices. Culture is regarded as having a negative effect on the transmission, prevention and treatment of HIV and AIDS. As much as there are studies that have explored culture as part of the challenges weakening the effective control of HIV and AIDS among young people, there seem to be minimal studies focusing on the perceptions of postgraduate university students regarding culture and HIV transmission, prevention and treatment. It is therefore against this backdrop that this study sought to explore the perceptions of postgraduate University students in Pretoria and Johannesburg on Culture and HIV and AIDS within the South African context. The study used a qualitative research approach, with a semi-structured interview schedule used as a research tool and one-on-one face-to-face in-depth interviews used as a data collection method. A total of 7 postgraduate university students took part in the study and were selected using purposive sampling technique. All interviews were audio recorded after gaining the formal consent from each participant. Data was analysed using thematic analysis. Findings show that culture plays a huge role in the way individuals behave and perceive certain things in life, and should be considered when dealing with issues related to HIV and AIDS transmission, treatment and prevention efforts in Gauteng. Conclusions drawn are that culture plays both a positive and a negative role in the transmission, prevention and treatment of HIV and AIDS. Recommendations are made in relation to programmatic interventions and future researchItem Examining the effects of HIV knowledge and perceived risk of HIV infection on condom use among youth: The case of South Africa(2016) Kaneli, Emelda ThabangHIV/AIDS continues to be a major health concern in Sub-Saharan Africa. South Africa, with an HIV prevalence of 10%, is one of the worst affected countries. The majority of new infections occur among young people aged 15-24 years and this is largely a result of not using condoms. The government and many NGOs have responded to this problem by introducing HIV education into the school curriculum and launching awareness campaigns and programmes. This was done with the expectation that an increase in HIV knowledge would lead to an increase in condom use among youth. Research based on the Health Belief Model has also found that people are more likely to adopt healthy behaviours if they think they are at risk of illness. In this regard perception of HIV infection among youth and the effect it has on condom use needs to be assessed. Objective The aim of the study was to investigate the relationships between HIV knowledge, perceived risk of HIV infection and condom use among youth aged 16-24 in South Africa. Methods The study was conducted using the National HIV Communication Survey of 2012 using a sample of 1795 sexually active males and females aged 16-24 years. For the descriptive statistics cross tabulations were conducted to assess the levels and distribution of condom use. Additionally, non-condom use rates were computed to assess the level of lack of condom use among youth. To investigate the association between HIV knowledge, perceived risk of HIV infection and condom use among youth a binary logistic regression was run at a bivariate and multivariate level. Results The study found that 38% of youth do not use condoms. The study also found that the association between lack of condom use and HIV knowledge was insignificant [p-value > 0.005], however the odds ratios show that as HIV knowledge increases there is a slight increase in condom use. The study found a significant association between perceived risk and lack of condom use [p-value < 0.005] however, the results show that youth who perceive themselves as being at risk of infection are less likely to use condoms. In addition the study found associations between lack of condom use and the other socio-demographic and relationship factors, namely, age, place of residence, province, education level, employment status, age at first sex, relationship status and knowledge of partners’ other sexual partners. Conclusion The study found that the association between HIV knowledge and condom use was insignificant, however there was a significant association between perceived risk of HIV infection and condom use at last sex. The results of the study has shown that it is important to increase HIV knowledge among youth but this is not enough to prevent HIV infection. More needs to be done particularly in regard to perception of risk of HIV infection.Item A retrospective review of the relationship between peritonsillar abscess and HIV(2010-10-12) Variava, ImraanHIV/AIDS continues to be an important public health challenge in sub Saharan Africa. It is estimated that approximately 68% of people living with HIV in the world are from this region [1]. South Africa has the largest infected population in the world, the adult (15-49 years) HIV prevalence is estimated at 17.64% [2]. It has been estimated that 40 - 70% of such HIV positive individuals present with head and neck manifestations, which include infection, inflammation and tumours, and are often the only and initial presenting sign [3,4]. Peritonsillar abscess is the most common deep infection of the head and neck in young adults and can occur in all age groups, but the highest incidence is in adults 20 to 40 years of age [5]. The aim of this study was to assess the relationship between peritonsillar abscess and the HIV status of patients. Method: An analytical cross sectional study utilising retrospective clinical data from ward registers, patient records, treatment registers and National Health Laboratory System (NHLS) databases. This study was conducted in the adult ENT ward at the Chris Hani Baragwanath Hospital and sample consisted of patient records over a 4 year period from January 2005 to December 2008. All patients admitted to the ENT ward with the discharge diagnosis of peritonsillar abscess that have been tested for HIV were included in this study. In this study period 450 patient files were reviewed of which 291 fulfilled the inclusion criteria. The demographic details, clinical presentation which included head and neck manifestations of HIV, the HIV status, management and complications of peritonsillar abscess were recorded. This data was analysed using STATA-10 software. Results: The age ranged from 15 to 63 years with a mean (SD) 29.3 years (9.58). From the 291 patients, 86 (29.55%) were HIV positive. This is significantly higher than the adult (15-49years) HIV prevalence rate of 17.64% [6]. The male: female ratio of HIV positive patients 1:1.53. Forty-nine (16.84%) patients presented with cervical lymph nodes of which 65.31% were HIV positive (P< 0.001). From the 86 HIV positive patients oral candida was present in 15.12% (P<0.001), lymphoma in 6.98% (P<0.001), oral hairy leukoplakia in 2.33%, Kaposi’s sarcoma in 1.16% and complications (parapharyngeal abscess) 3.48%. There was no statistical significance in the management of HIV positive patients, however hospital stay was longer with a mean of 3.802 days (P<0.001). From this study sample the HIV prevalence of 29.55% suggests that peritonsillar abscess may be an early clinical marker of HIV infection. Due to the high incidence of head and neck manifestations in HIV positive patients identifying a clinical marker (quinsy) in the earlier stages of HIV infection would allow for better screening, earlier diagnosis and treatment of HIV infection.Item Household and individual level factors associated with HIV infection in KwaZulu-Natal(2010-04-13T10:18:21Z) Bangre, OscarBackground: Sub-Saharan Africa continues to bear the brunt of the global HIV epidemic, with the epicentre located in Southern Africa. Of all the adult and children living with HIV globally in 2006, two-thirds (63%) were in sub-Saharan Africa.1 The epicenter of the HIV/AIDS epidemic in South Africa is located in the KwaZulu Natal province, where HIV incidence and prevalence continue to remain high and this has serious implications for HIV prevention and control programmes. Objectives i. To profile individuals who sero-converted during the period 2003-2007 in order to better target interventions. ii. To estimate the incidence rate for HIV during the period 2003 to 2007. iii. To identify factors associated with HIV infection at individual and household levels in Kwazulu-Natal. Methods This involved analysis data of a dynamic cohort study. The follow-up period was 2003-2007, and the study was a household-based HIV sero-prevalence survey of a population in Kwazulu Natal, South Africa, conducted by the Africa Centre for Health and Population Studies. The cohort comprised females aged 15 to 49 and males 15 to 54 years who participated in the baseline HIV sero-prevalence survey in 2003 and/ or subsequent surveys in 2005, 2006 and 2007. Individuals who participated in at least two surveys and had a negative HIV result on first enrolment were included in the analysis. Selected demographic, socio-economic, behavioural and geographic variables of the participants were obtained from the demographic surveillance system (DSS) database of the Africa Centre Demographic and Information System (ACDIS) for analysis. Profiles of recently HIV sero-converters were based on these variables and descriptive statistics used to compare the differences in sero-conversion between the different strata of each variable. Multiple logistic regression was used to investigate the association between variables of key interest. Results A total of 39, 738 individuals were surveyed for the four annual sero-prevalence surveys conducted from 2003-2007. Of these, 41.5% (n=16,491) were HIV negative on their first enrolment into the study, 11.6% (n=4610) were HIV positive on first enrolment, while 46.9% (n=18,637) had either participated in just one out of the four surveys, or were non-resident at baseline. These two categories of participants as well as those who tested HIV positive on first enrolment were dropped from the analysis. The final sample size used for analysis was 16,491 individuals and comprised 8,425(51.1%) females aged 15-49 years old and 8,066 (48.9%) males aged 15-54 years old. The incidence rate for HIV sero-conversion among the 16, 491 individuals included in the final analysis was 11.5 per 1000PYs during the follow-up period. In other words, 539 individuals sero-converted during 46818.15 person-years (PYs) at risk from 2003-2007. A significant proportion of the new HIV acquisitions (69.8%) occurred in households without any recently or previously infected household member, and women had a significantly greater risk of HIV infection(IR= 16.9 per 1000PYs; 95% CI: 15.33-18.640) compared to men(IR=5.9; 95% CI: 4.95-6.94) in this study area. Conclusion The younger age bracket (24-30 years old) was associated with significantly higher risk of HIV infection compared to the older age category. However, the age group 20-24 years bears the greatest burden of HIV pandemic in this community. Majority of seroconverters were rural dwellers but peri-urban dwellers had the greatest risk of HIV acquisition. The study also showed that attendance of a school or a training facility on a full-time basis during the follow-up period was protective for HIV acquisition compared. Also, attainment of standard 10 to 12 level of education was associated with a greater risk of HIV seroconversion. This can be attributed to the age of individuals at these levels of education and the associated high risk profile of this group. Living in close proximity to primary or secondary roads was also associated with a risk of HIV infection compared to those living far from major roads. This could be due to the ease of mobility and potential exposure multiple sex partners. This may be due to a desire for modern social amenities which requires financial wherewithal, which in turn facilitates transactional sex.Item Human rights discourses around the provision of antiretroviral drugs to HIV positive pregnant women in South Africa: implications for social work(2008-09-09T08:05:16Z) Tesfamichael, Misgina GebregiorgisThe study explores pertinent issues around a comprehensive provision of antiretroviral drugs to HIV positive pregnant women in South Africa from a human rights perspective. Although these drugs have been proven to significantly reduce the transmission of HIV from a pregnant mother to her newborn baby/babies at birth, the South African government for over five years refused to roll them out in the public health sector. Reasons that were provided in this regard were multifaceted and have included claims regarding their alleged toxicity, potential side effects, huge cost, inadequate infrastructure, etc until March 2004 when it announced to start a national rollout program. It is in light of this that the study sets out to explore some of the key positions within the government and amongst activist groups on the health rights of HIV positive pregnant women, and how these different positions have evolved in response to each other. In particular, the paper aims at examining how discourses of human rights were employed, and how they have impacted on the Social Work discipline. It further focuses on developing a Social Work perspective on the human rights of HIV positive pregnant women in South Africa, thereby contributing to the discipline’s professional value base and body of knowledge, which inform, inter alia, its advocacy role and social action approach. The research project was embedded in a theoretical framework often referred to as ‘standpoint research’. An archival study of local and international literature and policy documents was conducted. This was complemented with a limited qualitative study. Semi-structured interviews were conducted with a purposive sample of five interviewees representing a cross-section of positions on the topic. This data was analyzed using a three step coding procedure that allowed for categorizing, connecting, and systematically relating the gathered data to each other and to the reviewed literature. The research findings indicate that the South African government’s absence of consistency and apparent lack of political will to rollout the drugs have contributed to the deterioration of the right of HIV positive pregnant women to access health care services. The role of civil society organizations in helping to realize, promote and protect the health and related human rights of this group is emphasized. It was also found that the different strategies employed to this end speak well to Social Work’s value base, and some of its methods and approaches to practice. Social Work is therefore well placed to join and support those efforts of other segments of civil society that have been investigated in this paper. The paper concludes by making recommendations towards, inter alia, the need for the South African government to adhere to the values enshrined in the country’s Constitution; to work closely and transparently with different organs of civil society; and simultaneously implement the said ARV rollout program while building and strengthening its infrastructural capacity. The various roles Social Work could, and should, assume with regards to improving the human rights of HIV positive pregnant women in this regard are also highlighted.Item Gender differences in clinical and immunological outcomes in South African HIV-infected patients on HAART(2008-09-01T13:17:15Z) Maskew, MhairiABSTRACT Introduction South Africa is estimated to have the largest number of HIV infected adults in Southern Africa with a higher HIV prevalence in females compared to males. While significant reductions in morbidity and mortality due to HIV and AIDS have been realized for over a decade internationally, HIV treatment involving highly active antiretroviral therapy (HAART) is still a relatively new phenomenon in this country and gender differences in HIV outcomes between males and females in South Africa have not been previously well described. This study aimed to determine and describe gender differences in clinical and immunological outcomes in a population of HIV infected South African adults initiated on HAART. Materials and Methods This retrospective data analysis reviewed 6,617 HIV-infected adultsABSTRACT Introduction South Africa is estimated to have the largest number of HIV infected adults in Southern Africa with a higher HIV prevalence in females compared to males. While significant reductions in morbidity and mortality due to HIV and AIDS have been realized for over a decade internationally, HIV treatment involving highly active antiretroviral therapy (HAART) is still a relatively new phenomenon in this country and gender differences in HIV outcomes between males and females in South Africa have not been previously well described. This study aimed to determine and describe gender differences in clinical and immunological outcomes in a population of HIV infected South African adults initiated on HAART. Materials and Methods This retrospective data analysis reviewed 6,617 HIV-infected adults initiated on HAART at the Themba Lethu Clinic, an urban public-sector antiretroviral rollout facility in Johannesburg, South Africa between 1st April 2004 and 31st March 2007. Clinical data from these antiretroviral naïve patients was analysed for gender differences in mortality, rates of loss to follow up, CD4 cell count response, virologic suppression and weight gain. Cox regression models and logistic regression models were used to estimate hazard ratios (HR) and odds ratios (OR), respectively, for associations between gender and outcomes. Models were adjusted for age and baseline CD4 count. Results At baseline, 4,388 (66.3%) women were significantly younger (p<0.0001) and less likely to be employed than the 2,229 (33.7%) men (p<0.001). Furthermore, women had significantly higher baseline CD4 counts (p<0.0001) and higher body mass index (BMI) (p<0.0001). Males experienced significantly reduced survival compared to females (p=0.0053) by Kaplan-Meier analysis. In adjusted multivariate analysis, men were 22% more likely to die or become lost to follow up than women [HR = 1.22 (95% CI 1.06 - 1.39]. The period with the highest risk of mortality or loss to follow up was within six months of starting HAART. Female gender was associated with better CD4 count response. In multivariate analysis adjusted for age and baseline CD4 count, women were 35% more likely to achieve a 100 cell increase in CD4 count at four months after initiation of HAART [OR =1.35 (95% CI = 1.19 -1.54)] and 45% more likely to increase their CD4 counts by 100 cells/mm3 after ten months on HAART [OR =1.42 (95% CI = 1.20 -1.68)] when compared to men. Women were also more likely to achieve virologic suppression at ten months post HAART initiation [OR =1.54 (95% CI =1.21-1.97)] and were more likely to have gained weight after four months on treatment than males [OR = 1.26 (95% CI = 1.07–1.49)] after adjusting for age, baseline CD4 count and baseline BMI. Conclusions Women had significant advantages over men in terms of short-term clinical and immunological outcomes. Earlier access treatment for men should be facilitated and adherence should be promoted once on treatment. Further research is required to determine if these gender differences persist during long-term HAART.