Introduction: This study is a secondary data analysis of HIV/AIDS patients on Anti-retroviral Therapy (ART), at Themba Lethu HIV/AIDS clinic, who have had the first break in the continuity of taking their Antiretrovirals (ARVs) of more than 10 days, measured by patient missing the refill appointment for more than 10 days. The clinic started in 2004. HIV/AIDS is high in South Africa with about 400,000 AIDS patients on ARVs. For ARVs to be most effective they must be taken continuously without breaks, and for life. Without this, there is risk of ARVS drug resistance development and consequent failure of the ART program. Some patients may break this continuity and this seems to be a problem in South Africa. Where the patients develops side-effects or is not responding well to treatment, clinicians may also cause a break in the therapy. This study described the first break as when it occurred and for how long it lasted, investigated the factors associated with this break and the association of the first break and the last CD4 count. Materials and methods: 7,930 adults (≥18 years, either gender) on ART and baseline CD4 <250 cells/μl were included in the study. The study group were patients who had first break in continuity of therapy of more than 10 days. The first break was described as when it occurred after months of ART initiation and how long(days) the first break lasted. Patients on Post- Exposure Prophylaxis, single-dose Nevirapine, Prevention-of mother-To-Child- transmission therapy, and those with breaks in therapy of more than 364 days were excluded. Outcome variables was the last CD4 count. Analyses were in STATA 10, at 95% confidence interval. Median and quartile ranges were used to describe participants in the study. T-test, Fishers exact test and chi-square were used to compare groups. Regression was used to determine demographic and clinical factors associated with first break in therapy and also to determine the association of first break in therapy and the last CD4 count. Results: The median duration on ART for the patients was 764 days. 63% of patients had a break in ART. 47.5% of patients had their first break in therapy within the first 2 years of being on the ART program, with the largest proportion within the first 6 months of therapy. Most patient came with advanced disease(CD4 <100cells/μl, WHO clinical staging IV). Women were twice more than men. They tended to come earlier for therapy, took longer to improve and delayed in having the first break compared to men (254 vs. 205 days). Baseline hemoglobin and unemployment were factors associated with when the first break occurred. The median length of first break was 21 (Q1-Q3 7-43) Unemployment and baseline hemoglobin were associated with length of first break. The first break in therapy was associated with the last CD4 count. The longer the patient stayed on ART without the first break, the higher the last CD4 would be. Peripheral neuropathy had a statistically significant positive association with the last CD4 count. However, baseline CD4, Age, baseline BMI, WHO stage IV, baseline hemoglobin and unemployment had a statistically significant but negative association with the last CD4 count. The weakness of using the missing appointment system is that it does not inform clinician whether patients is really taking or not taking ARVs at home. Its strength over the self reported adherence system is that it is free of recall bias. Conclusion: Though Themba Lethu clinic has a follow-up system in place for patients missing refill appointment, up to 63% patient missed their appointment to collect medicine on time and this had a negative effect on the last CD4. There is need to strengthen existing follow-up method besides decentralising the ART services in Johannesburg.

Background In 2010, 2.2 million adolescents were living with HIV (Human Immunodeficiency Virus) worldwide. This study aimed to describe the socio-demographic and clinical characteristics of the adolescents (10-19 years old) initiating anti-retroviral treatment (ART) and to investigate characteristics that are associated with virological failure in adolescents on ART. Methods This was an analysis of adolescents initiating ART from June 2004-2010 at the Hlabisa Treatment and Care Programme in KwaZulu-Natal, South Africa. Data was collected from two datasets at Africa Centre for Health and Population Studies. Time to outcomes of death and lost to follow up (LTFU) were quantified using Kaplan-Meier estimates. The outcome was virologic response (< 70copies/ml) after at least 6 months on ART and the associations with an unsuppressed viral load were investigated using multivariable logistic regression. Results 543 adolescents, median age 15 years (IQR 12-18), initiated ART; 67.8% (368) were females. Age at treatment initiation showed a bimodal distribution, with a peak at 11 years and another at 17-19 years; 61 females aged 16-19 years initiated ART whilst pregnant. At baseline, median CD4 count was 152 cells/μl (IQR 72-251), 392 (72.2%) had prior TB and 129 (23.8%) a weight-for-age z-score ≤ -2 (i.e. were under-nourished). Numbers of adolescents starting ART increased from 53 in the years 2004-2006 to 196 in 2010. Overall mortality was 36.5 per 1000 person years (95% CI 27.2 - 48.8); LTFU 98.8 per1000 person years (95% CI 82.8-118). Adjusting for age and gender, LTFU was significantly higher in females initiating in late adolescence (15-19 years) (p<0.001) and 24 (39.3%) of those initiating ART whilst pregnant were LTFU. The first viral load after initiation was taken at a median time of 11.25 months (IQR 7.78-16.20). Of the 364 adolescents with a viral load result after at least 6 months of ART, 119 (32.7%) had an unsuppressed viral load (95% CI 27.9- 37.5). Adolescents who initiated in the year 2010 were found to have less odds of an unsuppressed viral load compared to those who initiated between 2004 and 2006 [adjusted Odds Ratio (aOR) 0.29 (95% CI 0.11-0.79)]. Those who had the first viral load test done after > 30 months of ART had higher odds of an unsuppressed viral load compared to those tested after 6-12 months of ART [ aOR 6.88 (95% CI 1.29-36.66)]. Conclusion Despite the yearly increase in adolescents initiating ART, good virological responses can be obtained through increased ART support to both individuals and health care providers. Timely viral load monitoring identifies those in need of increased adherence support on ART and may result in good virological responses. Recommendations Adolescents on ART are a vulnerable group that requires special attention to improve clinical and virological outcomes. Adolescent friendly ART clinics may be useful in providing this service and mitigate the high attrition rates of those on treatment for HIV. Public health awareness campaigns on HIV and its treatment may have a positive impact on virological response to ART and therefore campaigns targeting adolescents must be intensified. Early virological testing after 6 months on ART to monitor treatment responses helps to identify those with sub-optimal response to ART and reduce the progression to virological failure and drug resistance to anti-retroviral drugs.

Submitted in partial fulfilment of the requirements for the degree of Master of Public Health, in the field of Maternal and Child Health, to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, September 2014 / Introduction: Nevirapine (NVP) is used in combination antiretroviral treatment especially for pregnant HIV infected women. NVP has been shown to be inferior and more toxic than other similar drugs, but continues to be used in developing countries due to cost. Aim: This study aimed to determine the prevalence of NVP toxicity and associated factors among 478 pregnant women from three public health facilities in inner city Johannesburg. Materials and methods: We employed a cross-sectional retrospective record review study design to analyse the records of 478 pregnant women in the above mentioned public health facilities. Variables including demographic (age, weight, gestational age) and clinical (CD4 cell count, WHO HIV clinical stage, prior ART experience) characteristics were extracted and the association between these characteristics and the development of toxicity post NVP exposure was explored. Results: The study found that approximately nine out of ten women (89.5%) were ART naïve at the time of NVP initiation. When compared with ART naïve women, ART experienced women had a slightly higher mean CD4 cell count, however, for both groups of women, mean CD4 cell count was less than 250 cells/mm3. Overall, 85.1% of women had a CD4 cell count less than 250 cells/mm3. More than half (55.3%) of the women were in the third trimester of pregnancy and the majority (82%) classified as WHO HIV clinical stage one. At least one adverse event was reported in 63 (13.2%) women. Mild skin rash was the most prevalent adverse event, occurring in 9.6% of women. Hepatotoxicity occurred in 5.3% of women and severe skin rash occurred in 1.5% of women. Almost 85% of adverse events occurred in women with CD4 cell counts <250 cells/mm3. WHO HIV clinical stage II and IV were significantly associated with the overall development of toxicity (ρ <0.01). Conclusions: Whilst the overall prevalence of mild and severe skin rash in this sample was less than that demonstrated in earlier studies, a higher overall prevalence of hepatotoxicity was found. When compared with ART naïve women, ART experienced women were found to have a higher prevalence of mild skin rash. Hepatotoxicity and severe skin rash only occurred in ART naïve women. In this sample, CD4 cell count ≥250 cells/mm3 was not associated with the development of NVP adverse events. Recommendations: Our findings support the continued use of NVP as part of combination ART regimens in women of African descent. In contrast with previously published data, our study showed a significant association between WHO HIV clinical stage and NVP toxicity, our study also included relatively few women with higher CD4 cell counts. Further research including predominantly healthy HIV infected pregnant African women as well as women with higher CD4 cell counts is required in order to fully explore the association between these variables and the development of NVP post-exposure toxicity.

Background – The researcher conducted an explorative, qualitative study to identify the perceptions and experiences about ART of patients currently on treatment at Themba Lethu clinic (TLC) in Johannesburg in order to establish strategies to decrease the high level of non-adherence to antiretroviral therapy (ART). This study included 30 HIV positive patients on ART who came to Themba Lethu clinic for their regular clinic visit. The researcher used the purposive sampling procedure to target particular individuals and categories of individuals for investigation. Interviews and questionnaires were used as a method of collecting primary information. The researcher posed a series of questions to willing participants about their characteristics, opinions, attitudes, or previous experiences by and tabulates their answers. Results – The research finds that the participants ‘ages ranged from 26 – 62 years (M = 39.4). The participants stay in the suburbs around Johannesburg in Gauteng and 77% of them have been living there for more than 5 years. Only 40% of these patients were originally born in Gauteng while others come from different provinces in South Africa including some of the sub-Saharan countries (13%). The participants were less likely to have completed secondary education but were more likely to have completed Matric. 30% of participants are afraid of stigma, 40% are concerned about side-effects, 33.33% believes that ART cures AIDS, 70 % are non-adherent and 20% visited traditional healers while on ART. Conclusion – There must be on-going education, counseling and support to increase adherence and decrease the clinic loss to follow-ups. Intervention to improve care and treatment should utilize the role of traditional healers to reduce the disease progression and to improve adherence to ART. Traditional healers could also work more closely with modern health professionals to provide AIDS information and evaluation of HIV/AIDS symptoms.

In November 2003, the Department of Health launched the Operational Plan for Comprehensive Care, Management and Treatment (CCMT) for South Africa. This policy has as its central goal universal access to antiretroviral therapy to 1 million people living with HIV by the end of 2007. National implementation of the operational plan began in April 2004 and as at the end of October 2006, South Africa had initiated 213 828 people onto ART through the Plan, making it the biggest programme in the world. Of these, 55 580 people had been placed on treatment in Gauteng Province. Despite these early achievements, there are concerns as to whether the South African public health sector can rise to the challenge of universal access while achieving good clinical outcomes and programme performance. As Venter (2006: 298) states, “the health sector is buckling under the current load, and currently does not have the capacity to do anymore than dent the numbers needed to treat, unless a radical restructuring of health services occurs.” A crucial factor in providing a comprehensive approach to HIV/AIDS is the reorientation of service delivery from acute to chronic disease care. In addition to the shift in focus to chronic disease management of HIV/AIDS, health system constraints need to be addressed. These include inadequate health system infrastructure and human resources. This study aimed to comprehensively assess organisational capacity to provide antiretroviral therapy (ART) in two public sector CCMT sites in Gauteng Province and the influence of these organisational factors on follow-up and adherence to ART, with the view to understanding whether public sector CCMT sites are able to deal with new challenges posed by the Plan. The objectives were to assess: (1) levels of follow-up and adherence in patients registered at the CCMT site, (2) dimensions of organisational capacity, drawing on internationally recognised chronic disease care frameworks, namely the Wagner Chronic Care Model (CCM) and Innovative Care for Chronic Conditions (ICCC). These dimensions were: presence of motivated and adequately staffed teams; delivery systems design; the quality of support systems; and facility information systems. 3) the similarities and differences between the two sites with respect to organisational capacity, follow-up and adherence. The two sites were selected through a stratified (CHC and hospital) random sample of CCMT sites in Region A of the province, excluding the long–standing and well-established academic hospital CCMT sites in the sampling frame. The two sites, located in a District Hospital in the West Rand and a Community Health Centre (CHC) in Central Witwatersrand, were visited between May and July 2006. They had initiated 540 and 1001 patients on ART respectively since October 2004. A multi-method health service evaluation of capacity in the HIV related services (ART/Wellness, VCT, PMTCT, and TB) was conducted. This consisted of 11 semi-structured interviews with facility and programme managers; review of registers and routine facility data; an observation checklist and mapping to assess the physical infrastructure of the facility, presence of management and health information systems; 35 self administered questionnaires to assess the levels of motivation of nursing staff at each site. Data on self-reported adherence and viral loads were obtained from a separate study involving exit interviews with 356 patients who had been attending the services for at least four months in the two sites.1 Of the 540 and 1001 patients enrolled in the two services, 69.8% and 69.3% were still in the service after 18 months at the hospital and CHC, respectively. The monthly drop-out rate at the hospital had risen fairly sharply towards the end of the 18 month period, attributed by the staff to growing difficulties in access to the site by new enrolments. Nevertheless, based on self-reports (3- day recall period), viral load measures, and loss to follow-up, adherence levels at both sites appeared to be in line with national and international best practice. The percentage of patients with undetectable virus was 76.2% and 74.4% at the hospital and CHC, respectively. Staffing of the CCMT sites matched the pre-requisites outlined by the National Department of Health for a ‘core’ health care team treating 500 patients. The CHC CCMT site, however, had more than 500 patients on ART and moreover was providing two services within one unit, i.e. ART/Wellness and VCT thus increasing the patient load. Sites were reaching saturation and this was due to the lack of sufficient space coupled with the high volumes of patients, shortage of certain scarce skills (in particular pharmacy staff), and the multiple responsibilities of nursing staff. In general, the staffing situation at the hospital appeared better. More staff had joined than left the hospital over the year prior to March 2006, and clinical workloads both in the ambulatory services and the CCMT site were less than at the CHC. Vacancy rates were low, at 13.8% and 4.8% for the hospital and CHC, respectively. Strong leadership of CCMT sites by motivated ART programme managers was displayed; site managers were highly respected and revered by staff. Based on ratings in a self-administered questionnaire, overall levels of motivation and organisational commitment at both sites appeared good, although, worryingly, a sizeable proportion of respondents in both sites agreed with statement “I intend to leave this hospital/clinic.” Lack of external support (from the HIV/AIDS, STI, TB Programme) and debriefing systems for programme managers and nursing staff was identified as weaknesses. With some exceptions, both sites showed evidence of strong ‘horizontal’ mechanisms of referral and coordination between HIV and AIDS related services within sites; however the PMTCT programme at the hospital was less co-ordinated and networked with other services. In addition, ART and PMTCT programme managers at the hospital indicated that the relationship between hospital services and surrounding clinics was poor. Apart from the lack of space at the CHC CCMT site, support systems were adequate. There were no reported drug stock outs and supply of drugs and general supplies was good at both sites. Both sites were able to offer a range of routine and HIV specific tests. A combination of paper and electronic based information systems were used at both sites, however, the hospital CCMT site used a mixture of standard and locally designed data collection forms compared to the CHC which mainly used standard Department of Health forms. The information systems were adequate in monitoring and evaluating patients and programme performance; however, the study highlighted the absence of a clear patient register for individual and programme monitoring and only cross sectional patient data was reported. There was also considerable duplication at the hospital in collecting and compiling patient information. The findings of the study suggest that the two sites, located in the ‘routine’ public sector environment of Gauteng Province have demonstrated ability to build organisational capacity for ART provision, through a degree of systems integration and design, decision support systems, generation and local use of information and motivated local champions. Through these elements of organisational capacity, both sites have achieved good adherence rates. The key factors to achieving this good programme performance were motivated local champions who drove programmes forward and good working relationships between the CCMT and other players. In light of the weaknesses identified, the following key recommendations are proposed: Review sites to identify the reasons for the high-drop out rate and address these issues Due to evidence of early saturation at the CHC, it is suggested that additional roll-out sites be established, or alternatively increase staffing and space at the CHC to meet the needs of the high patient load. In addition, well patients should be decanted to lower level services e.g. community based care organisations, thus reducing the burden on the site Pay attention to the physical infrastructure needs of clinic based sites, especially as they become saturated Foremost, the current Employee Assistance Programme (EAP) implemented in Gauteng Province should be strengthened and marketed so that staff members are more aware of the service and make use of it accordingly. Alternatively, a culture of “caring for the caregivers” should be cultivated, through for example, specialist assistance, debriefing sessions, and better external programme support from HIV/AIDS, STI, TB (HAST) managers Improve support and supervision of ART programmes by facilitating greater communication and feedback between sites and district, national and provincial levels of government. Adopt a strategy of “task shifting”, through better use of lay workers, counsellors, and mid level workers such as pharmacy assistants. Facilitate greater integration and coordination between the PMTCT programmes and other services, including the provision of VCT and training of staff. In addition, it is imperative that there is good integration between services provided by local and provincial Departments of Health Simplify and standardise information systems, particularly the development of clear patient registers to allow for cohort analysis.

Despite the improved survival of human immunodeficiency virus (HIV) infected individuals with the introduction of highly active anti-retroviral therapy (HAART) in the South African public sector in 2004, new challenges have been brought to the fore. These include drug-related toxicities, particular those of stavudine, which remains in common use within developing countries. A prospective analysis of 9040 HIV-1-infected adults initiated on HAART from 2004 to 2007 at the Themba Lethu Clinic, Helen Joseph Hospital in Johannesburg, confirmed the ability to roll out a successful HAART programme in a resource limited environment with a high retention rate of 70%. Nearly 30% of patients switched to non-stavudine based regimens due to side effects - predominantly peripheral neuropathy, symptomatic hyperlactataemia and lipoatrophy. In an attempt to look for safer options, a prospective randomized controlled trial comparing standard and low dose stavudine with tenofovir was undertaken in 2009. Sixty patients were randomized 1:1:1 to either standard (30-40 mg), low (20-30 mg) dose stavudine or tenofovir (300 mg) each combined with lamivudine and efavirenz. Adipocyte mitochondrial DNA (mtDNA) levels, gene expression, anthropometry, markers of inflammation, lipid and glucose metabolism were assessed at various time intervals. Results demonstrate early mitochondrial depletion among black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared to patients on tenofovir. Mitochondrial toxicities occurred in both the stavudine arms. Immunological and virological outcomes were similar for all three arms. Both drugs caused lipid changes, but tenofovir had a more favourable effect on anthropometry and adipokines. Both stavudine regimens increased fasting insulin and C-peptide levels, with the higher stavudine dose also causing increased fasting glucose and HOMA levels. This study demonstrates an early association between mitochondrial depletion and stavudine therapy in the black South African population and shows that tenofovir has a minimal effect on mitochondrial numbers. Only two of eight adipocyte genes were significantly affected by stavudine therapy when compared with tenofovir, but this was only seen with the standard dose. This study highlights the occurrence of significant metabolic abnormalities with both drugs. Therefore, awareness of the potential increased cardiovascular risk should be of concern with tenofovir and stavudine, although toxicity is lower in the low dose compared to the standard dose stavudine regimen with no attenuation of anti-retroviral effectivity.

Research Report submitted in fulfillment of the requirements for the degree of Master in Public Health (MPH) at the University of the Witwatersrand. April 2015 / Introduction: Antiretroviral therapy (ART) is a lifesaving clinical intervention for people living with HIV (PLHIV). An important barrier to accessing therapy is the shortage of the health workforce particularly doctors. In order to mitigate the shortage, a nurse driven ART delivery approach known as Nurse Initiated and Managed Antiretroviral Therapy (NIMART) has been implemented in the public sector in South Africa and in other countries. NIMART enables professional nurses to initiate HIV positive persons on ART and manage their care at primary health care clinics. This study sought to explore and describe perceptions of operational managers, facility managers and professional nurses on the facilitators and barriers to the implementation of NIMART in the City of Joburg (CoJ) clinics. Methodology: This was an exploratory descriptive qualitative study which used in-depth interviews with a variety of respondents in order to gain insights into their perceptions of the implementation of NIMART in the CoJ clinics. In total, 26 respondents, comprising of operational managers, facility managers and professional nurses participated in the study. Thematic content analysis was used to analyse data drawing from the Donabedian structure-process-outcome framework. Results: The respondents identified the adequacy of NIMART training and mentoring; the availability and use of NIMART guidelines and the integration of NIMART into Primary Health Care (PHC) services as structural facilitative factors for NIMART implementation. The shortage of the health workforce, shortage of antiretrovirals (ARVs), poor referral feedback, food insecurity and the mobility of patients were identified as key structural and process barriers to the implementation of NIMART. Respondents perceived the improvement in quality of life of NIMART patients and the clinics’ ability to retain patients in care as indicative of the success of iii NIMART implementation. Finally, respondent’s suggestions for improving NIMART implementation in CoJ clinics focussed on improving shortage of the health workforce, improving the availability of ARV drugs and providing opportunities for continuing education for professional nurses. Discussion, conclusion and recommendations: In order to mitigate the barriers identified in this study, recommendations were that the City of Joburg should utilize lower level health care cadres such as nursing assistants and lay counsellors to reduce the professional nurses’ workload and thus improve access to treatment. In addition, the City of Joburg should revise the antiretroviral drug allocations to clinics and revise delivery schedules to ensure that clinics do not run out of ARV drugs. The referral feedback process should be strengthened through the referring clinic and the referral hospital jointly developing referral protocols that should be used by both institutions. Finally, the City of Joburg should consider conducting consultative discussions with professional nurses prior to introduction of new programmes and provide opportunities for regular updates for operational managers, facility managers and professional nurses. Future research could look at the role of PHC qualification in the implementation of NIMART.

Thesis (D Phil. (Medical Virology))--2008. / Background and Objectives: South Africa is one of the countries highly affected by human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Some drugs (e.g. lamivudine) used as part of combination antiretroviral regimens for HIV treatment have dual activity against HBV and HIV. Despite high infection rate with both viruses, routine screening for HBV before initiation of treatment for HIV is not yet a standard practice. This study undertook to investigate: (1) the burden of HBV co-infection in HIV-positive patients enrolling for highly active antiretroviral therapy (HAART) at Dr George Mukhari hospital, (2) the impact of anti-HBV containing HAART regimens on HBV during the management of HBV/HIV co-infected patients, (3) the co-evolution of HBV and HIV drug-resistant strains, and (4) the correlation of HBV genotypes with response to anti-HBV containing HAART regimens. Study Population and Methods: To investigate the burden of HBV/HIV co-infections, a cohort of 192 HIV patients who were candidates for ARV treatment at Dr George Mukhari hospital were studied by screening for HBV serological markers (HBsAg, anti-HBs and anti- HBc) (Elecsys 2010, Roche Diagnostics) and HBV DNA with an in-house nested PCR assay targeting HBV polymerase gene. Quantitation of HBV DNA positive samples was performed with Roche Cobas Taqman HBV test 48 assay. To investigate the impact of lamivudine-containing HAART regimens on HBV during the management of HBV/HIV co-infected patients, as well as the coevolution of HBV and HIV drug-resistant strains, a total of 78 patients were studied. HBV virological response against lamivudine containing-HAART regimens [1a (lamivudine, stavudine and efaverenz); 1b (lamivudine, stavudine and neviripine)] was measured (Cobas Taqman HBV test 48, Roche diagnostics). HBV direct sequencing targeting HBV polymerase gene was performed on all baseline samples (n=78) and additional samples collected at various time points (n = 45). Direct sequencing was also performed on 30 HIV baseline samples targeting the HIV reverse transcriptase and protease genes (Spectru-Medix SCE 2410 Genetic Analysis System and ABI PRISM® 3100 Genetic Analyzer version 3.7). To explore the genetic diversity of HBV and HIV strains circulating in Pretoria and surrounding areas, as well as the correlation of HBV genotypes with response to lamivudine-containing-HAART regimens in co-infected patients, all baseline and follow-up HBV and HIV sequences were analysed, compared and correlated with treatment. Sequence alignments and phylogenetic studies for both HBV and vi HIV were conducted with MAFFT, Mega 4 and neighbour joining phylogenetic trees generated with the PHYLIP programme. Results: Three significant findings were observed in this study. Firstly, the majority of South African HIV patients enrolling for HAART were exposed to HBV infection and either had acute or chronic HBV infections. A total of 63.0% of patients were found to have one or more HBV markers, with 40.6% having detectable HBV DNA as an indication of replication. The study also detected 22.9% with positive HBsAg, and 23% of 77% HBsAg-negative patients having occult hepatitis B infection. Secondly, HBV/HIV co-infected patients do benefit during the management of HIV infections with lamivudine-containing HAART regimens. A total of 68.4% of patients responded to HAART, with undetectable HBV DNA during 18 to 24 months of follow-up. A total of 91.3% of HIV patients also responded to HAART with an undetectable HIV viral load during 6 to 12 months of follow-up. However, a total of 18% of patients had persistent HBV DNA, yielding various HBV virological responses against lamivudine containing-HAART regimens. This proportion of patients poses a question regarding the management of HBV and HIV coinfections, as guidelines on the use of HAART with anti-HBV activity from developed countries, may not necessarily be followed in developing countries. The results further showed that baseline drug-resistance was more frequent with HIV than HBV in this cohort of patients. The following HIV primary drug resistant mutants were observed: nine major NRT's primary mutants, M41L (1/30), E44A (1/30), V75M (1/30), F77L (1/30), V118I (1/30), M184V (1/30), L210S (1/30), T215Y (1/30) and V90I (1/30), and five major NNRT’s primary mutants were also detected, K103N (3/30), Y318CFSY (1/30), E138Q (1/30), P225H (1/30) and K238T. However, all followup samples had undetectable HIV viral load. In contrast to HIV, only one patient was detected with HBV mutant, M204I, at baseline. The mutant reversed to wild type during 6 months and other follow-up (12, 18 and 24 months). Finally, this study indicated that the HBV genotype A is still the most prevalent genotype circulating in South Africa. Of the 78 HBV sequences, 77 were genotype A and 1 sequence was genotype G. This is the first report from Africa of the detection of HBV genotype G. HIV subtype C remains the predominant prevailing subtype in South Africa. HBV genotype or HIV subtype C was not observed to influence any treatment outcome following treatment with vii lamivudine-containing HAART regimens. The study also indicated that patients on lamivudinecontaining HAART regimens do benefit not only by suppressing HIV and HBV viral load, but also improving immunity (i.e. CD4 cells count increases). Conclusion: Overall, the present study highlights the need for screening HBV before initiation of any HAART containing anti-HBV regimens in HBV/HIV co-infected patients. It necessitates the use of molecular assays for effective laboratory in diagnosis of occult HBV infections in HIVpositive patients, especially in developing countries where these assays are not widely available. While lamivudine-containing HAART regimens do benefit both HBV and HIV patients in co-infected individuals, however, whether HBV virological response is temporary or sustained is unknown at this stage. What is certain is that these patients require an effective monitoring programme as (1) a small percentage experience variable HBV virological responses (partial, reactivation, or no response), and (2) hepatitic flares are likely to develop if HAART is terminated (e.g. by patient), or the current HAART regimen is switched to another regimen without anti-HBV activity. HBV genotype A remains the dominant genotype in South Africa, but novel genotypes can be detected. HIV subtype C was found to be the prevalent subtype. HBV genotype or HIV subtype C were not seen to influence any treatment outcome following treatment with lamivudine-containing HAART regimens. Recommendations: HIV patients should be screened for HBV before initiation of anti-HBV containing HAART regimens. The screening of HBV in HIV patients is also important since some drugs included as part of HAART (e.g. nevirapine) may cause hepatotoxicity and exacerbate HBV infections leading to increased morbidity and mortality due to liver complications. Immunization and immune boosters of HIV patients with low (< 10IU/L) or no immunity against HBV should be done as this could be beneficial, although these patients may not respond optimally, or their immunity may wane faster due to immunocompromised status. Monitoring of both HBV and HIV resistant strains should be conducted for timely detection for the occurrence of multiple resistant mutations, which could limit future therapeutic option for both viruses.

Thesis (MPH (Faculty of Medicine))--University of Pretoria, 2006. / Abstract in English. Includes bibliographical references .

Thesis (Ph.D.)--Drexel University, 2009. / Includes abstract and vita. Includes bibliographical references (leaves 79).