Thesis (M Med.(Obstetrics & Gynecology))--University of Limpopo,2009. / OBJECTIVE: The objectives of the study were: 1) To determine the pattern of toxicity/side-effects among women using Highly Active Antiretroviral Therapy (HAART) in the perinatal period in comparison with women who were treated with intra- partum prophylaxis of nevirapine at the time of delivery. 2) To evaluate the effects of either approach of therapy on maternal and fetal outcomes. METHODOLOGY: STUDY DESIGN The department of Obstetrics and Gynaecology has begun to administer HAART to pregnant women identified for ARV programme. These women were counseled and recruited prospectively for the study. The study involved comparison of pregnancy outcomes between women identified for HAART and those who were HIV infected but who only required intra-partum prophylaxis in labour to prevent mother-to-child transmission of HIV with nevirapine.

Thesis (MPH))--University of Limpopo (Medunsa Campus), 2011. / Botswana was the first country in Africa to aim to give antiretroviral treatment to all its HIV positive deserving citizens in 2001. This brought about a significant improvement in survival and quality of life of HIV infected patients as well as a dramatic decrease in the incidence of opportunistic infections. However, although many reports about metabolic abnormalities and abnormal body fat distribution among people on ART have been published elsewhere, little is known about this in Botswana. The purpose of this study was to investigate the prevalence and factors associated with development of metabolic syndrome among people with HIV on ART at the IDCC Clinic at Princess Marina Hospital, Gaborone, Botswana. Methods This was a cross-sectional study based on patient interviews and review of records. A structured questionnaire and a data collection form were used to collect data on demographic, socioeconomic, lifestyle, clinical and laboratory data. Metabolic Syndrome was defined using the International Diabetes Federation (IDF) criteria. Patients who consented to participate were interviewed and their records were reviewed to collate data. Only patients that had been on treatment from January to December 2010 were included. Results A total of 190 subjects participated in the study, 141 (74.2%) females and 49 (25.8%) males. The age of the participants ranged from 24 to 71 with a median age of 40.5 years (IQR: 35 – 49). The overall prevalence of metabolic syndrome in this study was 11%. Metabolic syndrome was associated with traditional risk factors such as hypertension and high triglycerides; but with some unique features such as age, current employment and current NRTI use were also identified. In the bivariate analysis to identify the determinants of metabolic syndrome, the odds for developing MS were higher among participants who were married, employed, on a salary and used ART regimens containing NRTIs. High cholesterol, fasting blood glucose and triglycerides were also associated with the development of metabolic syndrome. There was a significant association with age as people over 45 years were significantly shown to have metabolic syndrome than the younger ones. The median age of participants who had metabolic syndrome was higher at 45 years (IQR: 39 – 53 years) that those without metabolic syndrome at 40 years (IQR: 34 – 48). Married participants were 13 times more likely to develop MS than their unmarried counterparts [OR (95%CI)]: 13 (1.91 - 88.35), p=0.009]. Participants who were employed and had a salary as their source of income were 27.54 times more likely to develop MS although the difference was not statistically significant. The type of regimen affected the prevalence of metabolic syndrome; in fact Up to 17 of the 21 participants with metabolic syndrome used a combination of drugs with NRTIs and NNRTIs as well as PI in 8 cases. So the use of a protease inhibitor based ART regimen increased the odds of developing MS by 51.57 times [OR (95%CI)]: 51.57 (1.55 – 1709.64), p=0.027]; while in case of NRTIs the odds were 78.53 times more for the likelihood to develop MS [OR (95%CI)]: 78.53 (1.10 – 5565.50), p=0.044]. Although there was no significant association between the duration of ART and the development of metabolic syndrome; the median duration of ART among participants with metabolic syndrome was higher at 68 months (IQR: 51 – 80) compared to those without metabolic syndrome at 56 months (IQR: 40 – 68). With regard to sex, 16.3% of the male participants had metabolic syndrome compared to 9.2% among the females; but the difference was not statistically significant. Conclusion In conclusion, the prevalence of metabolic syndrome was low, affecting only 11% of the study participants. The factors associated with the occurrence of the syndrome were the male sex, the long duration on treatment, being married, employed, and over 45 years old. The most significant factors were being on NRTIs and PIs containing regimens. These findings suggest that patients on antiretroviral treatment with the above characteristics should be monitored regularly for metabolic syndrome.

Thesis (MPH))--University of Limpopo (Medunsa Campus), 2010. / Introduction: HIV-positive parents taking antiretroviral therapy are faced with the difficult decision of whether and what details to share about their HIV status with their children. They need to decide if, when, and how they will disclose their illness to their children. Many reasons have been identified which influence parents’ decision to disclose their HIV status to their children. Aim and objectives: The aim of the study was to explore parental decision and experiences of disclosing or not disclosing their HIV status to children and to explore strategies used by non-disclosed parents to conceal their HIV status from their children. Methodology: Using a qualitative approach, six focus group discussions were conducted with a sample of disclosed and non- disclosed biological parents of children aged between 7-18 years. Participants were recruited from a wellness clinic at the Dr George Mukhari where they routinely collect antiretrovirals. A total of 44 parents (13 biological fathers and 31 mothers) were recruited and participated in two focus groups with disclosed parents, three with non disclosed parents and a pilot focus group interview with disclosed and non disclosed parents. Findings: Disclosure to children was difficult and occurred within a context influenced by death, dying and discrimination. Despite parents being on ARVs, fear of death and dying continues to influence disclosure to children. HIV related practices like taking ARVs and child feeding practices predisposes parents to stigma and discrimination and was major reason for non-disclosure to children, family and neighbours. Whereas previously, prior to the availability of ARVs, parents disclosed to prepare children to face parental death, now disclosure occurs for children to support parents in adherence and when they are sick. The need for support is not surprising given that for parents who disclosed immediately, disclosure was prompted by ill health. The primary reason parents delayed disclosure is because they do not know how to tell the child. One other concern was that disclosure will makes children responsible for caring for parents. By delaying disclosure parents were protecting their children mostly from being hurt, from social rejection and discrimination and from fear of mother’s death. Conclusion: Regardless of whether parents had disclosed or not disclosed the decision to disclose was difficult and emotional for parents, and is influenced by various factors. Due to stigma and discrimination disclosure in most families is often treated as a secret; parents do everything possible to protect their HIV status. Common strategies used to protect their HIV status include hiding antiretrovirals, removing labels from ARV bottles, use of different packages for ARVs, taking medication privately and substituting TB for HIV. Parents believed that by delaying disclosure they were protecting their children from consequences of disclosure. Most children reacted positively to disclosure and were protective and supportive to parents, while some non disclosed children became suspicious of parental status. Recommendations: There is need for the development of health service practices that would protect HIV positive people taking ARVs from stigma and discrimination. Most HIV positive parents currently on ARVs have seronegative and seropositive children. They therefore need to develop strategies to discuss managing HIV illness especially with their seropositive children who also need to have their diagnosis disclosed. It is imperative that disclosure guidelines are developed to guide parents in disclosing HIV to children. Key words: Parental, disclosure, non disclosure, HIV positive, children, qualitative research.

Thesis ((MSc(Med)(Pharmacy))--University of Limpopo (Medunsa Campus), 2011. / Background: Anecdotal evidence from fixed Voluntary Counselling and Testing (VCT) centres within the public sector indicates, that many patients are lost in the transition from VCT to Human Immunodeficiency Virus (HIV) care and treatment. The actual number of patients who are eligible for antiretroviral ttreatment (ART) after a positive HIV test, but who do not visit the antiretroviral (ARV) clinic to initiate ART, is currently not known. The need to identify the extent of this problem was therefore evident. Objectives: To investigate and describe the procedures and records used at the VCT centres under study. To identify the proportions of patients who fail to proceed through the different steps of the process from VCT to initiation on ART within a period of six months. To make recommendations for interventions aimed at improving the tracking of patients from the VCT entry point to ART initiation. Methods: The study was conducted as an operational research project at Odi and Stanza Bopape VCT centres. The design of the study was descriptive. Data were collected retrospectively and prospectively over a period of four months. Operational procedures and documentation systems at both VCT centres were observed. The records of all patients who tested HIV positive from 1 April 2009 to 30 June 2009 at Odi and Stanza Bopape VCT centres were identified from the VCT registers and selected for the study. Patients who were eligible for ART were identified based on their CD4 count. Eligible patient names were crossreferenced against the SOZO system (electronic patient database) to determine whether they had attended their pre-treatment visits at the ART clinic and whether ARV medicines had been dispensed to them for the first time. Where there was no proof that the patient attended the pre-treatment visits or finally accessed ART at an ARV clinic within six months, the patient was regarded as lost to initiation on ART. Results: The results obtained from the observational phase of the study showed differences in the procedures followed at the two VCT centres. At Odi VCT centre, patients referred for VCT by medical doctors only had an ELISA test and had to return on a different date for the ELISA test results, while patients visiting the VCT centre voluntarily first had a Rapid test and if positive they had an ELISA test on the same day. At Stanza Bopape VCT centre, patients referred by doctors and patients visiting the VCT centre voluntarily had a Rapid test and an ELISA test after a positive Rapid test. The patients at Odi had their CD4 test results interpreted by the nurse at the VCT centre while at Stanza Bopape the results were interpreted by the doctor at the ARV clinic. x iv The study included a cohort of 743 patients who tested HIV positive from April 2009 to June 2009 at Odi and Stanza Bopape VCT centres. Of these patients 344 tested at Odi VCT centre and 399 were tested at Stanza Bopape. The majority of patients at the two VCT centres were female (55% at Odi VCT centre and 59% at Stanza Bopape VCT centre), unemployed and single. At both VCT centres, patients were expected to return for collection of CD4 results within two weeks of the HIV test. At Odi VCT centre, 159 (49.4%; n=322) patients did not return to collect their CD4 results. Of those who returned, only 41.1% (67; n=163) returned within one month. At Stanza Bopape VCT centre 52.8% (210; n=399) patients did not collect their CD4 results. Of the patients who collected their CD4 count results, 51.3% (97; n=189) collected within one month. The Fisher’s exact test revealed no statistically significant difference (P=0.410) between the two VCT centres in terms of patients who returned for their CD4 results collection and those who did not return. More than half of the patients with accessible CD4 counts at Odi presented late for VCT. This was shown by 65.4% (n=275) of patients with CD4 count 200 cells/mm3 during HIV diagnosis. At Stanza Bopape VCT centre 46.6% (n=386) also had CD4 count 200 cells/mm3. The difference in terms of late presentation between the patients from the two clinics was statistically significant (P<0.001; Fisher’s exact test). The ART initiation rate at both VCT centres was found to be low. More than half of the patients eligible for treatment (CD4 200 cells/mm3) at both VCT centres did not initiate ART. This was shown by 59.4% (n=180) of patients at Odi VCT centre and 67.8% (n=180) of patients at Stanza Bopape VCT centre who did not initiate ART. There was no significant difference (P=0.317; Fisher’s exact test) between the two VCT centres in terms of the patients who did not initiate ART. Conclusion: A high percentage of patients who presented for VCT and were eligible for treatment were lost to initiation on ART. The majority of these patients did not return to collect their CD4 results and thus were lost immediately after VCT. These results suggest a need for an urgent intervention that will improve ART uptake. Recommendations: Patients referred by doctors for VCT at Odi VCT centre should have a Rapid test, and if positive they should have an ELISA and CD4 test on the same day to prevent the loss of patients before they even identify their HIV status. The option of a ‘one stop’ VCT and immediate CD4 results, should be further explored due to the unacceptable patient default rates at both VCT centres. A CD4 count machine which x v will provide results immediately on the same day of the test should be utilised. There must be sufficient personnel and equipment to follow-up on patients who do not return for their CD4 results, pre-treatment counselling and ART. The SOZO system should be integrated between the VCT centres and the ARV clinics to improve the flow of patient information between the VCT centre and the ARV clinic. A qualitative study should be conducted to explore reasons for patients not returning to collect their CD4 results. Key words: VCT; loss to initiation; non-uptake; lost in transition; HIV and AIDS

Thesis (MPH) -- University of Limpopo (Medunsa Campus), 2011. / Background Available and affordable second-line antiretroviral treatment regimens are a key component of universal access to treatment and its continuation. However, providing second-line ART is affected by a number of factors including infrastructure, skills and cod competency of available personnel, cost and availability of second-line drugs. Like first-line antiretroviral agents, second-line drugs have also inherent toxicities. While these have been described in adults, few studies reported this in children. Hence, the need to conduct this study. The aim of the study was to characterize the adverse effects on second-line antiretroviral therapy among HIV infected adults and adolescents and children treated at Mildmay Uganda (MUg). Method This was a cross-sectional study based on the review of patients' records. Data was extracted from client medical charts of patients on second-line antiretroviral treatment regimens treated at Mildmay Uganda Centre from January 2000 to December 2008. Results In total, 247 cases, the majority (90.7%) of the study participants were aged 13 years and above, female (53.0%), and single (68.0%). With regard to reasons that led to the second-line regimen, the main reason for switching was treatment failure (83%), followed by toxicity (5.7%), and other reasons such as the onset of Kaposi Sarcoma disease, maintaining regimen after transfer, and nevirapine pre-exposure. Overall, 55 out of 247 patients suffered from one or more adverse effects, a prevalence of 22.3%. The mean number of adverse drug reactions (ADR) was 1.3 per patient. Of the 55 who experienced adverse effects, 76.4% experienced one type of adverse effect. The three most common adverse effects were gastro-intestinal, followed by hematological and peripheral neuropathy. Based on age, while adults experienced a broad range of adverse 11 drug reactions including metabolic and hepatic ADRs besides the three cited above; children experienced two types only, gastrointestinal, and hematological ADRs. Hematological ADRs were significantly more prevalent in children than adults (66.7% versus 21.4%); they were also more prevalent in females than males (30.8% versus 15.2%). In contrast, while metabolic ADRs were equally distributed, peripheral neuropathy was more prevalent in males than females (30.3% versus 20.5%). Based on the number of ADRs experienced, more males than females (19.8% versus 14.5%) experienced one type of adverse effect whereas more females than males (6.1% versus 4.3%) experienced two to three adverse drug reactions to second-line regimens. Clinically, the didanosine-based regimens were the most associated with ADRs in both children and adults. In Children, the regimen, ABC/DDI/LPV/R, was responsible of 66.7% of ADRs documented; while in adults it was involved in 60.3% of ADRs. Similarly, TDF-, zidovudine-, and stavudine-based regimens were also involved respectively in 52.9%, 17.8%, and 14.7% of ADRs. Based on gender, didanosine-containing regimen, with either TDF or stavudine with lopinavir/r were responsible of 66.7% of ADRs reported in males; while TDF-based regimen with lamivudine or FTC were involved in 21.1% of ADRs also in males. In females, didanosine-, TDF-, zidovudine-, and stavudine-based regimens were also involved respectively in 57.9%, 36.9%, 23.7%, and 7.9% of ADRs. The regimen, TDF/DDI/LPV/R, was also the most associated with the occurrence of ADRs in females as it was in males. Moreover, although no difference was found among patients whose bodyweights increased significantly and those whose did not, patients whose CD4 counts increased significantly experienced more ADRs than those whose had not (8.8% versus 1.3%, p= 0.03). Conclusion Overall, second-line regimens seem to be well tolerated as the overall prevalence of adverse effects was 22.37%. The didanosine-containing regimens were most associated with the occurrence of ADRs. Hematological ADRs were more prevalent in children than 12 adults; and more in females than males. In contrast, while metabolic ADRs were equally distributed, peripheral neuropathy was more prevalent in males than females. These findings emphasize the need to individualize treatment based on the characteristics of the patient.

Thesis (M Med (Family Medicine)) -- University of Limpopo, 2010. / Depression commonly Occurs in chronic diseases such as HIV-AIDS and "Depression makes chronic disease worse: WHO", depression is expected to become the second-leading cause of disease burden by the year 2020, after heart disease. Depression can exacerbate chronic disease (WHO, 2007, Kerr L.K. & Kerr L.D., 2001). From the University of New Mexico Health Sciences Center (2009), it has been confirmed that depression is very common in people living with HIV/AIDS and the rate of depression among them was estimated as high as 60%. This was previously confirmed by Moosa and Jeenah (2007).' In Tanzania life events were found to be part in the aetiology of depression and that the rates had increased in recent years (Mbatia et aI., 2009).The authors recommend the strengthening of training of primary health care workers to detect depression and provide pharmacological and psychological treatment. The South African Journal of Psychiatry, states that depression in the world is exceedingly common in the general population. The lifetime prevalence rates are between nine to 20%. In chronic diseases the rate of depression is between 15 to 360/0,which is high. (Moosa & Jeenah, 2007). Untreated depression can lead to missing medication doses and lower the patient's quality of life (aidsinfonet.org, 2009). It has also been established that depression is linked to poor Highly Anti¬retroviral Therapy (HAART) adherence (Kacanek D., Jacobson D.L., Spiegelman D., Wanke c., Isaac R. & Wilson LB., 2010). Primary care based aualitv improvement programs for depression have shown to improve the quality of care, satisfaction with care and health outcomes, functioning, economic productivity and household wealth at reasonable cost (WHO 2010, Kumar & Encinosa W., 2009, Hoberg M.A. et aI., 2008). Study setting The study was conducted in the Rustenburg district of North West province. The comprehensive management of HIV/AIDS is part of the district health system that is implemented in this province. Voluntary Counselling and Testing (VCT) is offered to patients at the clinics or health centre (Primary Health care facilities). A positive rapid test, done in the clinic or health centre, is followed by collection of blood for confirmation, using a second rapid test and two Enzyme linked immuno sorbent assay (ELISA) and assessing CD4 levels at the h.ospital's laboratory. Patients with two rapid tests and two ELISA positives, and a CD4 of less than 200 or clinical stage three, according to revised World Health Organisation (WHO) clinical staging of HIV/AIDS (J.G. Barlett, J.E. Gallant & F.M. Conradie, 2008) are referred to wellness clinic / Job Shimankana Tabane (JST) hospital, for initiation of Anti¬Retroviral Therapy (ART). Once stable on treatment for more than six months, patients are referred down to the nearest clinic or health centre for follow up. Why is the study necessary? As a medical officer at one of the down referral primary health care facilities, the researcher encountered patients who were on antiretroviral therapy, that frequently presented with symptoms consistent with depression but these patients were not aware of the depression. x The researcher became concerned about the lack of identification of depression among adult patients on antiretroviral therapy for human immunodeficiency virus (HIV) in my district, with subsequent lack of appropriate management. After conducting an informal enquiry from some of the patients about symptoms that could be attributed to depression, the researcher became convinced that most of the patients were depressed, although they were not aware of it. The magnitude of the problem had not been explored in Rustenburg before. This is when the researcher decided to conduct a study on screening for depression amongst adult patients on antiretroviral therapy for human immunodeficiency virus in my district. The result of this study will inform the development of protocols used in the provision of comprehensive care to these patients. Methodoloav A descriptive cross-sectional study was conducted amongst adult patients on antiretroviral therapy for Human Immunodeficiency Virus (HIV) who attended one clinic and two health centres, all three accredited in terms of HIV management, in Rustenburg district (South Africa) during December 2009. A hundred and seventeen (117) adult patients, who consulted three Health Centres and agreed to participate in the study were sequentially selected for inclusion in the study. A questionnaire, adapted from the World Health Organization's (WHOs), Zung self-rating depression score by a trained nurse, was used to evaluate depression among the participants. Descriptive analysis of the data was done. The Medical Research, Ethics and Publications Committee (MREC) of the University of Limpopo/ Medunsa campus approved the intended study (Registration Number: MREC/M/29/2009). Results Amongst the 117 participants 81(69.2 %) had mild depression, 2 (1.7%) had moderate depression, 1(0.9 %) had severe depression and 33 (28.2%) did not have depression. Depression was equally common amongst males and females, 77.1% for males and 69.5% for females. Depression was most common on patients taking a regimen that contains efavirens, lamivudine and stavudine. Conclusion Depression is common among adult patients on antlretroviral therapy for Human Immunodeficiency Virus (HIV) attending primary health care facilities in Rustcenburg District. Most of the patients are mildly depressed, as demonstrated by this study research.

Thesis (MPH)--University of Limpopo, 2013. / Statistics from Pigg’s Peak Hospital, in Swaziland, continue to show an improvement in the uptake of HIV testing among TB patients, as well as a very high rate of HIV co-infection among the TB patients. The unit’s reports also show a low uptake of antiretroviral therapy among the HIV co-infected TB patients, and high death rates. Most of these deaths occur among HIV co-infected TB patients who have not yet initiated ART despite being on TB treatment. Anecdotal evidence suggests that there is reluctance and refusal by a considerable proportion of TB/HIV co-infected patients to take TB treatment and ART concurrently, and that they prefer to commence ART after completing TB treatment. No study has ever been conducted in Swaziland to determine the reasons for refusal of ART initiation prior to the completion of TB treatment among HIV co-infected TB patients. Aim The aim of this study was to explore the reasons for refusing antiretroviral therapy among HIV co-infected tuberculosis patients, prior to the completion of tuberculosis treatment, at Pigg’s Peak Hospital, in Swaziland. Methods A qualitative descriptive study was conducted in order to generate information on the subjects’ experiences and views on the concurrent taking of tuberculosis and antiretroviral medicines. A sample of nineteen HIV co-infected TB patients was purposefully selected to answer the research question. Results The most common reasons given by the respondents for refusing ART initiation during TB therapy were their un-readiness for ART, especially because ART must be taken for life, the perception that one was still in good health, the fear of adverse outcomes being precipitated by combining ART with TB medicines, a preference of traditional medicines, and health systems-related problems. Other reasons were: a lack of food, substance abuse, a fear of the increased pill burden, a denial of the HIV-positive status, and problems related to treatment supporters. Conclusion In TB/HIV co-infection care settings, comprehensive Pre-ART counseling must be integrated with interventions that address the specific barriers to ART initiation faced by clients; to improve the acceptability of ART initiation during TB therapy to these HIV/TB co-infected patients.

The spectrum of drugs used in HIV-infected patients has dramatically changed since triple antiretroviral combinations were introduced, albeit at the expense of some severe adverse events, in 1996. Long term complications of antiretroviral drug exposure, such as HIV lipodystrophy, as well as organ-specific disease of heart and bone are, therefore, a critical issue when designing antiretroviral regimens. Because it is difficult to predict the occurrence of lipodystrophy, and because there is no therapeutic agents able to combat lipodystrophy once established, avoidance of thymidine nucleoside analogues remains the most useful strategy to prevent and treat lipoatrophy; although this approach can worsen dyslipidaemia. Metabolic syndrome can and should be assessed as it predicts type 2 diabetes as well as cardiovascular events in HIV-infected individuals. Ongoing HIV replication is a risk factor for serious non-AIDS events including cardiovascular disease, as well as for AIDS. Therefore, HIV RNA suppression is imperative in all patients requiring antiretroviral therapy. Finally, HIV-infected adults on antiretroviral therapy, particularly in those receiving a boosted protease inhibitor, have a high prevalence of low bone mineral density. The estimation of fracture risk with the WHO FRAXTM tool deserves further validation in HIV-infected adults.

During the course of HIV pathogenesis, the virus induces multiple defects in immune cells, altering their functional ability to efficiently control HIV itself and other infections. Whilst the widespread implementation of antiretroviral therapy (ART) has led to reduced morbidity and mortality in most HIV-infected individuals having access to treatment, we still do not know whether full restoration of immune function occurs. The aim of this study was to assess the extent to which ART restores both phenotypic and functional T and B cell immunity. HIV-infected women were studied before and 1 year after ART initiation. In Chapter 2, the effect of ART on T cell activation and differentiation profiles was evaluated in HIV-infected individuals (n=28; pre- and post-ART), and compared to HIVuninfected age- and sex-matched controls (n=23). In Chapter 3, the restoration of copathogen specific CD4+ T cells was determined by comparing their cytokine secretion ability and memory differentiation profiles in response to Mycobacterium tuberculosis and cytomegalovirus in HIV-infected (n=15; pre- and post-ART), compared to uninfected (n=9) individuals. Finally, Chapter 4 examined changes in B cell activation and memory profiles in HIV-infected persons (n=19; pre- and post- ART), and compared profiles to HIV-uninfected individuals (n=19). Multiparameter flow cytometry was performed to address the study objectives. T cell activation, as measured by CD38 and HLA-DR expression, was significantly reduced one year after ART for both CD4+ and CD8+ T cells, but normalisation to levels in HIV-uninfected individuals did not occur, despite suppression of viral load. In addition, skewed CD4+ and CD8+ T cell memory profiles were not completely restored. Furthermore, no change in the cytokine production capacity and memory profile of pathogen-specific CD4+ T cells was found before and after ART, but pathogen-specific CD4+ T cells exhibiting a late differentiated profile (CD27- CD45RO+) had a lower ability to replenish (p=0.02; r = -0.5) compared to cells with an early differentiated profile (CD27+CD45RO+; p=0.04; r = 0.45) prior to ART. Similar to T cells, activated B cells (CD40+CD86+) were only partially normalised post-ART, and remained significantly higher than B cells of HIV-uninfected individuals. The frequency of all B cell memory subsets were comparable between HIV-treated and uninfected individuals, with the exception of plasmablasts, whose frequency was still significantly higher than in HIV-uninfected subjects. In summary, these results demonstrate that HIV-infected women on suppressive ART show a substantial but only partial normalisation of T cell and B cell memory subsets, and lower levels of T cell and B cell activation. In addition, restoration of co-pathogen specific memory CD4+ T cells upon treatment was dependent on their memory profile before ART. Understanding the impact of HIV on T and B cell dysfunction and restoration upon ART may provide important insights into the mechanisms of HIV pathogenesis in the era of ART.

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. People living with HIV are particularly susceptible to TB infection, and treatment of HIV-TB co-infection is challenging for multiple reasons, including potential drug-interactions. Drug-resistant TB is difficult to treat and is associated with high treatment failure rates, mainly because the antimycobacterial drugs currently available are ineffective against drug-resistant TB. Bedaquiline is a new antimycobacterial drug which has shown great promise through its excellent efficacy for treating drug-resistant TB. Being a new drug, however, potential drug interactions with antiretrovirals are a major concern. Bedaquiline is metabolized in the liver by an enzyme called cytochrome P450 3A (CYP3A). The antiretrovirals nevirapine, efavirenz, and lopinavir/ritonavir (LPV/r) can affect the activity of this enzyme, and consequently affect the concentration of bedaquiline in the patient's blood. Nevirapine and efavirenz increase the activity of CYP3A, which may result in increased metabolism of bedaquiline, thus decreasing the concentration of bedaquiline, with consequent risk of treatment failure or the further development of drug-resistance. LPV/r inhibits the CYP3A enzyme, which may result in decreased bedaquiline metabolism, thus causing high concentration of bedaquiline in the blood, with consequent risk of toxicity. We conducted a pharmacokinetic study in 43 adult patients with drug-resistant TB to evaluate the drug-interactions between bedaquiline and the antiretrovirals nevirapine and LPV/r. We did serial measurements of the bedaquiline concentration in their plasma over 48 hours, and compared these concentrations in patients who were on antiretroviral and those who were not on antiretrovirals. Our results showed that nevirapine had no significant effect on bedaquiline concentrations, while patients on LPV/r had bedaquiline concentrations 2 fold higher than patients not on antiretrovirals. We could not determine the clinical significance of this, but recommend that patients receiving LPV/r and bedaquiline in combination must be closely monitored for side-effects.