OpenUCT :: Browsing by Subject "Antiretroviral therapy"

Browsing by Subject "Antiretroviral therapy"

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Open Access
Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages
(Public Library of Science, 2014) Weiden, Michael D; Hoshino, Satomi; Levy, David N; Li, Yonghua; Kumar, Rajnish; Burke, Sean A; Dawson, Rodney; Hioe, Catarina E; Borkowsky, William; Rom, William N; Hoshino, Yoshihiko
While exploring the effects of aerosol IFN-γ treatment in HIV-1/tuberculosis co-infected patients, we observed A to G mutations in HIV-1 envelope sequences derived from bronchoalveolar lavage (BAL) of aerosol IFN-γ-treated patients and induction of adenosine deaminase acting on RNA 1 (ADAR1) in the BAL cells. IFN-γ induced ADAR1 expression in monocyte-derived macrophages (MDM) but not T cells. ADAR1 siRNA knockdown induced HIV-1 expression in BAL cells of four HIV-1 infected patients on antiretroviral therapy. Similar results were obtained in MDM that were HIV-1 infected in vitro . Over-expression of ADAR1 in transformed macrophages inhibited HIV-1 viral replication but not viral transcription measured by nuclear run-on, suggesting that ADAR1 acts post-transcriptionally. The A to G hyper-mutation pattern observed in ADAR1 over-expressing cells in vitro was similar to that found in the lungs of HIV-1 infected patients treated with aerosol IFN-γ suggesting the model accurately represented alveolar macrophages. Together, these results indicate that ADAR1 restricts HIV-1 replication post-transcriptionally in macrophages harboring HIV-1 provirus. ADAR1 may therefore contribute to viral latency in macrophages.
Open Access
Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa
(Public Library of Science, 2010) Brinkhof, Martin W G; Spycher, Ben D; Yiannoutsos, Constantin; Weigel, Ralf; Wood, Robin; Messou, Eugène; Boulle, Andrew; Egger, Matthias; Sterne, Jonathan A C; (IeDEA), for the International epidemiological Database to Evaluate AIDS
BACKGROUND: Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up. Methods and FINDINGS: Treatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9-6.5%) to 10.9% (9.6-12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9-11.6%) to 16.9% (15.0-19.1%), with relative increases in mortality ranging from 27% to 73% across programmes. CONCLUSIONS: Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.
Open Access
Altered ratio of IFN-γ/IL-10 in patients with drug resistant Mycobacterium tuberculosis and HIV-tuberculosis immune reconstitution inflammatory syndrome
(Public Library of Science, 2012) Skolimowska, Keira H; Rangaka, Molebogeng X; Meintjes, Graeme; Pepper, Dominique J; Seldon, Ronnett; Matthews, Kerryn; Wilkinson, Robert J; Wilkinson, Katalin A
We have described a clinical relationship between HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) and anti-tubercular drug resistance. Here we studied the immune response of TB-IRIS patients from whom a drug-resistant (n = 11) or drug-susceptible (n = 25) Mycobacterium tuberculosis (MTB) strain was isolated after presenting with TB-IRIS. ELISpot analysis and multiplex cytokine analysis of the supernatant collected from peripheral blood mononuclear cells stimulated overnight with the heat-killed H37Rv MTB laboratory strain was used. Although there was no statistical difference in IFN-gamma ELISpot responses between the two groups, the results point towards higher bacterial load in the drug-resistant patients, possibly due to failed therapy. The ratio between secreted IFN-gamma/IL-10 and IL-2/IL-10 was significantly lower in TB-IRIS patients in whom the cause of TB was a drug-resistant strain compared to those with a fully sensitive strain (p = 0.02). Since host immune responses are dependent on the bacterial load, we hypothesise that the impaired cytokine balance is likely to be caused by the poorly controlled bacterial growth in these patients.
Open Access
Anti-retroviral therapy increases the prevalence of dyslipidemia in South African HIV-infected patients
(Public Library of Science, 2016) Dave, Joel A; Levitt, Naomi S; Ross, Ian L; Lacerda, Miguel; Maartens, Gary; Blom, Dirk
Purpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.
Open Access
Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis
(Public Library of Science, 2012) Suthar, Amitabh B; Lawn, Stephen D; Del Amo, Julia; Getahun, Haileyesus; Dye, Christopher; Sculier, Delphine; Sterling, Timothy R; Chaisson, Richard E; Williams, Brian G; Harries, Anthony D
In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection.
Open Access
Antiretroviral therapy in a community clinic - early lessons from a pilot project
(Health and Medical Publishing Group, 2003) Bekker, Linda-Gail; Orrell, Catherine; Reader, Larissa; Matoti, Larissa; Cohen, Karen; Martell, Rob; Abdullah, Fareed; Wood, Robin
Objectives. To report on operational and clinical problems encountered during the first 6 months of a community-based antiretroviral therapy (ART) programme. Methods. ART was implemented in a primary care setting utilising an easily replicable service-delivery model based on a medical officer and nurse. Therapeutic counsellors, themselves HIV-infected, provided counselling and adherence support. Drug and monitoring costs were charitably funded and provincial health authorities supplied the medical infrastructure. The HIV Research Unit, University of Cape Town, supplied training and additional clinical support. Local HIV primary care clinics provided patient referrals. Standardised ART regimens were used with strict entry criteria (AIDS or CD4 count < 200 cells/µl). Results. Demand for the service was high. Referred patients had advanced disease (AIDS 57%, median CD4 count 96/µl) and high pre-treatment mortality (83/100 person-years). Mycobacterial disease was a major contributor to this mortality (40%). Scheduled clinic visit hours were six times higher during recruitment than maintenance. Attributable costs were: drugs 61%, staff 27%, viral load and CD4 cell counts 10% and safety monitoring 2%. Viral load after 16 weeks of therapy was < 400 copies/ml in the first 16 patients. Conclusions. ART can be successfully implemented within a primary care setting. Drug purchases and staff salaries drive programme costing. The service model is capable of managing 250 - 300 patients on chronic ART, but staffing needs to be increased during recruitment. Attention must be given to the diagnosis of tuberculosis during screening and early ART. Incorporating therapeutic counsellors into the programme increased community involvement and utilised a valuable and previously untapped resource.
Open Access
Antiretroviral therapy outcomes among adolescents and youth in rural Zimbabwe
(Public Library of Science, 2012) Bygrave, Helen; Mtangirwa, Judith; Ncube, Kwenzakwenkosi; Ford, Nathan; Kranzer, Katharina; Munyaradzi, Dhodho
Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.
Open Access
Antiretroviral therapy, especially Efavirenz, is associated with low bone mineral density in HIV-infected South Africans
(Public Library of Science, 2015) Dave, Joel A; Cohen, Karen; Micklesfield, Lisa K; Maartens, Gary; Levitt, Naomi S
Purpose We determined the prevalence and correlates of low bone mineral density (BMD) in HIV-infected South Africans as there is a paucity of such data from Africa. METHODS: BMD and serum 25-hydroxyvitamin D were measured in HIV-positive participants on antiretroviral therapy (ART) and in those not yet on ART (ART-naïve). RESULTS: We enrolled 444 participants [median age 35(IQR: 30, 40) years; 77% women]. BMD was low (z score <-2SD) in 17% and 5% of participants at the lumbar spine and total hip, respectively. Total hip [0.909 (SD 0.123) vs 0.956 (SD 0.124) g/cm 2 , p = 0.0001] and neck of femur BMD [0.796 (SD 0.130) vs 0.844 (SD 0.120) g/cm 2 , p = 0.0001] were lower in the ART, compared to the ART-naïve group. Vitamin D deficiency was present in 15% of participants and was associated with efavirenz use [adjusted OR 2.04 (95% CI 1.01 to 4.13)]. In a multivariate linear regression, exposure to efavirenz or lopinavir-based ART was associated with lower total hip BMD, whereas higher weight, being male and higher vitamin D concentration were associated with higher total hip BMD (adjusted R 2 = 0.28). Age, weight, sex, and the use of efavirenz-based ART were independently associated with lumbar spine BMD (adjusted R 2 = 0.13). CONCLUSIONS: Vitamin D status, use of efavirenz or lopinavir/ritonavir, weight, age and sex are significantly associated with lower BMD in this young cohort of HIV-infected South Africans.
Open Access
Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods
(Public Library of Science, 2011) Kranzer, Katharina; Lewis, James J; White, Richard G; Glynn, Judith R; Lawn, Stephen D; Middelkoop, Keren; Bekker, Linda-Gail; Wood, Robin
BACKGROUND: Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported. METHODS: This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods. RESULTS: The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data. CONCLUSION: The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.
Open Access
Antiretroviral treatment outcomes amongst older adults in a large multicentre cohort in South Africa
(Public Library of Science, 2014) Fatti, Geoffrey; Mothibi, Eula; Meintjes, Graeme; Grimwood, Ashraf
Introduction Increasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ≥55 years) vs. younger adults (aged 25-54 years) in routine care settings in South Africa. METHODS: A multicentre cohort study of ART-naïve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models. RESULTS: 4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR = 1.34 (95% CI: 1.29-1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR) = 1.44 over 5 years (95% CI: 1.26-1.64), particularly for the period 7-60 months of treatment, asHR = 1.73 (95% CI: 1.44-2.10). LTFU was lower in older adults, asHR = 0.87 (95% CI: 0.78-0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio = 1.42 (95% CI: 1.23-1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios = 0.69 (95% CI: 0.56-0.85) and 0.64 (95% CI: 0.47-0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3-33.2) lower in older adults. CONCLUSIONS: Although older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies.
Open Access
Assessment at antiretroviral clinics during TB treatment reduces loss to follow-up among HIV-infected patients
(Public Library of Science, 2012) Pepper, Dominique J; Marais, Suzaan; Bhaijee, Feriyl; Wilkinson, Robert J; De Azevedo, Virginia; Meintjes, Graeme
Setting: A South African township clinic where loss to follow-up during TB treatment may prevent HIV-infected TB patients from receiving life-saving ART. Objective: To determine factors associated with loss to follow-up during TB treatment. Design: Regression analyses of a cohort of ART-eligible TB patients who commenced TB treatment and were followed for 24 weeks. RESULTS: Of 111 ART-eligible TB patients, 15 (14%) died in the ensuing 24 weeks. Of the remaining 96 TB patients, 11 (11%) were lost to follow-up. All TB patients lost to follow-up did not initiate ART. Of 85 TB patients in follow-up, 62 (73%) initiated ART 56 days after TB diagnosis (median, IQR 33-77 days) and 31 days after initial assessment at an ART clinic (median, IQR: 18-55 days). The median duration from TB diagnosis to initial assessment at an ART clinic was 19 days (IQR: 7-48 days). At 24 weeks, 6 of 85 (7%) TB patients who presented to an ART clinic for assessment were lost to follow-up, compared to 5 of 11 (45%) TB patients who did not present to an ART clinic for assessment. Logistic regression analysis (adjusted odds ratio = 0.1, 95% confidence interval [95% CI]: 0.03-0.66) and our Cox proportional hazards model (hazard ratio = 0.2, 95% CI: 0.04-0.68) confirmed that assessment at an ART clinic during TB treatment reduced loss to follow-up. CONCLUSION: Assessment at antiretroviral clinics for HIV care by trained health-care providers reduces loss to follow-up among HIV-infected patients with TB.
Open Access
The association between aids related stigma and major depressive disorder among HIV-positive individuals in Uganda
(Public Library of Science, 2012) Akena, Dickens; Musisi, Seggane; Joska, John; Stein, Dan J
BACKGROUND: Major depressive disorder in people living with HIV/AIDS (PLWHA) is common and may be associated with a number of factors, including AIDS-related stigma, decreased CD4 levels, increased opportunistic infections and sociodemographic variables. The extent to which AIDS-related stigma is associated with major depressive disorder among PLWHA has not been well studied in sub-Saharan Africa. The objective of this study was to examine the associations between major depressive disorder, AIDS-related stigma, immune status, and sociodemographic variables with the aim of making recommendations that can guide clinicians. METHODS: We assessed 368 PLWHA for major depressive disorder, as well as for potentially associated factors, including AIDS-related stigma, CD4 levels, presence of opportunistic infections, and sociodemographic variables. RESULTS: The prevalence of major depressive disorder was 17.4%, while 7.9% of the participants had AIDS related stigma. At multivariable analysis, major depressive disorder was significantly associated with AIDS-related stigma [OR = 1.65, CI (1.20-2.26)], a CD4 count of ≥200 [OR 0.52 CI (0.27-0.99)], and being of younger age [0.95, CI (0.92-0.98). CONCLUSIONS: Due to the high burden of major depressive disorder, and its association with AIDS related stigma, routine screening of PLWHA for both conditions is recommended. However, more research is required to understand this association.
Open Access
Association of lopinavir concentrations with plasma lipid or glucose concentrations in HIV-infected South Africans: a cross sectional study
(BioMed Central Ltd, 2012) Sinxadi, Phumla; McIlleron, Helen; Dave, Joel; Smith, Peter; Levitt, Naomi; Maartens, Gary
BACKGROUND: Dyslipidaemia and dysglycaemia have been associated with exposure to ritonavir-boosted protease inhibitors. Lopinavir/ritonavir, the most commonly used protease inhibitor in resource-limited settings, often causes dyslipidaemia. There are contradictory data regarding the association between lopinavir concentrations and changes in lipids.AIM:To investigate associations between plasma lopinavir concentrations and lipid and glucose concentrations in HIV-infected South African adults. METHODS: Participants stable on lopinavir-based antiretroviral therapy were enrolled into a cross-sectional study. After an overnight fast, total cholesterol, triglycerides, and lopinavir concentrations were measured and an oral glucose tolerance test was performed. Regression analyses were used to determine associations between plasma lopinavir concentrations and fasting and 2 hour plasma glucose, fasting cholesterol, and triglycerides concentrations. RESULTS: There were 84 participants (72 women) with a median age of 36 years. The median blood pressure, body mass index and waist: hip ratio were 108/72 mmHg, 26 kg/m2 and 0.89 respectively. The median CD4 count was 478 cells/mm3. Median duration on lopinavir was 18.5 months. The median (interquartile range) lopinavir concentration was 8.0 (5.2 to 12.8) mug/mL. Regression analyses showed no significant association between lopinavir pre-dose concentrations and fasting cholesterol (beta-coefficient 0.04 (95% CI 0.07 to 0.00)), triglycerides (beta-coefficient 0.01 (95% CI 0.04 to 0.02)), fasting glucose (beta-coefficient 0.01 (95% CI 0.04 to 0.02)), or 2-hour glucose concentrations (beta-coefficient 0.02 (95% CI 0.09 to 0.06)). Lopinavir concentrations above the median were not associated with presence of dyslipidaemia or dysglycaemia. CONCLUSIONS: There was no association between lopinavir plasma concentrations and plasma lipid and glucose concentrations.
Open Access
Association of lopinavir concentrations with plasma lipid or glucose concentrations in HIV-infected South Africans: a cross sectional study
(BioMed Central Ltd, 2012-10-26) Sinxadi, Phumla Z; McIlleron, Helen M; Dave, Joel A; Smith, Peter J; Levitt, Naomi S; Maartens, Gary
Abstract Background Dyslipidaemia and dysglycaemia have been associated with exposure to ritonavir-boosted protease inhibitors. Lopinavir/ritonavir, the most commonly used protease inhibitor in resource-limited settings, often causes dyslipidaemia. There are contradictory data regarding the association between lopinavir concentrations and changes in lipids. Aim To investigate associations between plasma lopinavir concentrations and lipid and glucose concentrations in HIV-infected South African adults. Methods Participants stable on lopinavir-based antiretroviral therapy were enrolled into a cross-sectional study. After an overnight fast, total cholesterol, triglycerides, and lopinavir concentrations were measured and an oral glucose tolerance test was performed. Regression analyses were used to determine associations between plasma lopinavir concentrations and fasting and 2 hour plasma glucose, fasting cholesterol, and triglycerides concentrations. Results There were 84 participants (72 women) with a median age of 36 years. The median blood pressure, body mass index and waist: hip ratio were 108/72 mmHg, 26 kg/m2 and 0.89 respectively. The median CD4 count was 478 cells/mm3. Median duration on lopinavir was 18.5 months. The median (interquartile range) lopinavir concentration was 8.0 (5.2 to 12.8) μg/mL. Regression analyses showed no significant association between lopinavir pre-dose concentrations and fasting cholesterol (β-coefficient −0.04 (95% CI −0.07 to 0.00)), triglycerides (β-coefficient −0.01 (95% CI −0.04 to 0.02)), fasting glucose (β-coefficient −0.01 (95% CI −0.04 to 0.02)), or 2-hour glucose concentrations (β-coefficient −0.02 (95% CI −0.09 to 0.06)). Lopinavir concentrations above the median were not associated with presence of dyslipidaemia or dysglycaemia. Conclusions There was no association between lopinavir plasma concentrations and plasma lipid and glucose concentrations.
Open Access
Availability of antiretroviral therapy is associated with increased uptake of HIV testing services
(2005) Mfundisi, Coceka; Chiranjan, Nirasha; Rodrigues, Charl; Kirchner, Launel; Bock, Peter; Myer, Landon
Voluntary counselling and testing (VCT) is an important tool in HIV prevention efforts and in the identification of HIV-infected individuals for care and treatment services. But despite the central role of VCT in the response to HIV/AIDS, less than 20% of South Africans have been tested for HIV. Although there are substantial barriers to seeking VCT, including quality of services and AIDS-related stigma, improving VCT rates remains a critical part of the response to the HIV/AIDS epidemic. Recently there has been particular interest in the potential influence of access to antiretroviral therapy (ART) on demand for HIV testing services. It has been suggested that the availability of effective treatment for HIV/AIDS may help motivate individuals to find out their HIV status. However, this possibility remains largely hypothetical and there have been few studies investigating this question. In light of the importance of VCT as an entry point to HIV prevention interventions and treatment services, the possible impact of ART availability on VCT uptake has major implications for the public health response to HIV/AIDS in South Africa. We investigated whether the availability of ART was associated with HIV testing among individuals attending the site B day hospital in Khayelitsha near Cape Town, the setting for a well-publicised antiretroviral pilot.
Open Access
Barriers to initiation of antiretrovirals during antituberculosis therapy in Africa
(Public Library of Science, 2011) Pepper, Dominique J; Marais, Suzaan; Wilkinson, Robert J; Bhaijee, Feriyl; De Azevedo, Virginia; Meintjes, Graeme
BACKGROUND: In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB). The initiation of antiretroviral therapy (ART) during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART. Method Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years) who commenced TB therapy, were eligible for ART, and were followed for 6 months. FINDINGS: Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25-43%) did not initiate ART. Male gender and younger age (<36 years) were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25-10.95] and 3.3 [95%CI: 1.12-9.69], respectively). Death during TB therapy was associated with a CD4+ count <100 cells/µL. CONCLUSION: In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients - particularly young men - did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.
Open Access
Better antiretroviral therapy outcomes at primary healthcare facilities: an evaluation of three tiers of ART services in four South African provinces
(Public Library of Science, 2010) Fatti, Geoffrey; Grimwood, Ashraf; Bock, Peter
BACKGROUND: There are conflicting reports of antiretroviral therapy (ART) effectiveness comparisons between primary healthcare (PHC) facilities and hospitals in low-income settings. This comparison has not been evaluated on a broad scale in South Africa. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was conducted including ART-naïve adults from 59 facilities in four provinces in South Africa, enrolled between 2004 and 2007. Kaplan-Meier estimates, competing-risks Cox regression, generalised estimating equation population-averaged models and logistic regression were used to compare death, loss to follow-up (LTFU) and virological suppression (VS) between PHC, district and regional hospitals. 29 203 adults from 47 PHC facilities, nine district hospitals and three regional hospitals were included. Patients at PHC facilities had more advanced WHO stage disease when starting ART. Retention in care was 80.1% (95% CI: 79.3%-80.8%), 71.5% (95% CI: 69.1%-73.8%) and 68.7% (95% CI: 67.0%-69.7%) at PHC, district and regional hospitals respectively, after 24 months of treatment ( P <0.0001). In adjusted regression analyses, LTFU was independently increased at regional hospitals (aHR 2.19; 95% CI: 1.94−2.47) and mortality was independently elevated at district hospitals (aHR 1.60; 95% CI: 1.30−1.99) compared to PHC facilities after 12 months of ART. District and regional hospital patients had independently reduced probabilities of VS, aOR 0.76 (95% CI: 0.59−0.97) and 0.64 (95% CI: 0.56−0.75) respectively compared to PHC facilities over 24 months of treatment. Conclusions/Significance: ART outcomes were superior at PHC facilities, despite PHC patients having more advanced clinical stage disease when starting ART, suggesting that ART can be adequately provided at this level and supporting the South African government's call for rapid up-scaling of ART at the primary level of care. Further prospective research is required to determine the degree to which outcome differences are attributable to either facility level characteristics or patient co-morbidity at hospital level.
Open Access
Cardio-thoracic ratio is stable, reproducible and has potential as a screening tool for HIV-1 related cardiac disorders in resource poor settings
(Public Library of Science, 2016) Esmail, Hanif; Oni, Tolu; Thienemann, Friedrich; Omar-Davies, Nashreen; Wilkinson, Robert J; Ntsekhe, Mpiko
BACKGROUND: Cardiovascular disorders are common in HIV-1 infected persons in Africa and presentation is often insidious. Development of screening algorithms for cardiovascular disorders appropriate to a resource-constrained setting could facilitate timely referral. Cardiothoracic ratio (CTR) on chest radiograph (CXR) has been suggested as a potential screening tool but little is known about its reproducibility and stability. Our primary aim was to evaluate the stability and the inter-observer variability of CTR in HIV-1 infected outpatients. We further evaluated the prevalence of cardiomegaly (CTR≥0.5) and its relationship with other risk factors in this population. METHODOLOGY: HIV-1 infected participants were identified during screening for a tuberculosis vaccine trial in Khayelitsha, South Africa between August 2011 and April 2012. Participants had a digital posterior-anterior CXR performed as well as history, examination and baseline observations. CXRs were viewed using OsiriX software and CTR calculated using digital callipers. RESULTS: 450 HIV-1-infected adults were evaluated, median age 34 years (IQR 30-40) with a CD4 count 566/mm 3 (IQR 443-724), 70% on antiretroviral therapy (ART). The prevalence of cardiomegaly was 12.7% (95% C.I. 9.6%-15.8%). CTR was calculated by a 2 nd reader for 113 participants, measurements were highly correlated r = 0.95 (95% C.I. 0.93-0.97) and agreement of cardiomegaly substantial κ = 0.78 (95% C.I 0.61-0.95). CXR were repeated in 51 participants at 4-12 weeks, CTR measurements between the 2 time points were highly correlated r = 0.77 (95% C.I 0.68-0.88) and agreement of cardiomegaly excellent κ = 0.92 (95% C.I. 0.77-1). Participants with cardiomegaly had a higher median BMI (31.3; IQR 27.4-37.4) versus 26.9; IQR 23.2-32.4); p<0.0001) and median systolic blood pressure (130; IQR 121-141 versus 125; IQR 117-135; p = 0.01). CONCLUSION: CTR is a robust measurement, stable over time with substantial inter-observer agreement. A prospective study evaluating utility of CXR to identify cardiovascular disorder in this population is warranted.
Open Access
Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa
(2016) Njuguna, Christine; Swart, Annoesjka; Blockman, Marc; Maartens, Gary; Chisholm, Briony; Stewart, Annemie; Uys, Anri; Cohen, Karen
Abstract Background Gynaecomastia is associated with exposure to antiretroviral therapy (ART), in particular efavirenz. There is limited data on clinical characteristics of patients with ART-associated gynaecomastia in resource-limited settings and little guidance on the optimal management of this adverse drug reaction (ADR). We describe the clinical characteristics, management and outcomes of gynaecomastia cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa. Methods We identified all gynaecomastia cases in adolescent boys and men on ART reported to the hotline between June 2013 and July 2014. We collected follow up data telephonically at monthly intervals to document clinical management and outcomes. Results We received 51 reports of gynaecomastia between June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the hotline. All patients were on efavirenz-based ART. Mean age was 34 years (standard deviation 12) and seven were adolescents. The median onset of gynaecomastia was 15 months after efavirenz initiation (interquartile range 6–42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%). Serum testosterone was quantified in 25 of 35 patients with follow up data, and was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in 29/35 patients (83%) and gynaecomastia improved in 20/29 (69%). Conclusions Gynaecomastia was a frequently reported ADR in our setting, occurring with prolonged efavirenz exposure. Testosterone was low in the minority of tested cases. Most clinicians elected to switch patients off efavirenz, and gynaecomastia improved in the majority.
Open Access
Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa
(BioMed Central, 2016-11-16) Njuguna, Christine; Swart, Annoesjka; Blockman, Marc; Maartens, Gary; Chisholm, Briony; Stewart, Annemie; Uys, Anri; Cohen, Karen
Background: Gynaecomastia is associated with exposure to antiretroviral therapy (ART), in particular efavirenz. There is limited data on clinical characteristics of patients with ART-associated gynaecomastia in resource-limited settings and little guidance on the optimal management of this adverse drug reaction (ADR). We describe the clinical characteristics, management and outcomes of gynaecomastia cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa. Methods: We identified all gynaecomastia cases in adolescent boys and men on ART reported to the hotline between June 2013 and July 2014. We collected follow up data telephonically at monthly intervals to document clinical management and outcomes. Results: We received 51 reports of gynaecomastia between June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the hotline. All patients were on efavirenz-based ART. Mean age was 34 years (standard deviation 12) and seven were adolescents. The median onset of gynaecomastia was 15 months after efavirenz initiation (interquartile range 6–42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%). Serum testosterone was quantified in 25 of 35 patients with follow up data, and was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in 29/35 patients (83%) and gynaecomastia improved in 20/29 (69%). Conclusions: Gynaecomastia was a frequently reported ADR in our setting, occurring with prolonged efavirenz exposure. Testosterone was low in the minority of tested cases. Most clinicians elected to switch patients off efavirenz, and gynaecomastia improved in the majority.