Browsing by Subject "Antiretrovirals"

Now showing 1 - 17 of 17
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    A cluster randomized controlled trial of extending ART refill intervals to six-monthly for anti-retroviral adherence clubs
    (2019-07-30) Wilkinson, Lynne; Grimsrud, Anna; Cassidy, Tali; Orrell, Catherine; Voget, Jacqueline; Hayes, Helen; Keene, Claire; Steele, Sarah J; Gerstenhaber, Rodd
    Abstract Background The antiretroviral therapy (ART) adherence club (AC) differentiated service delivery model, where clinically stable ART patients receive their ART refills and psychosocial support in groups has supported clinically stable patients’ retention and viral suppression. Patients and health systems could benefit further by reducing visit frequency and increasing ART refills. We designed a cluster-randomized control trial comparing standard of care (SoC) ACs and six-month ART refill (Intervention) ACs in a large primary care facility in Khayelitsha, South Africa. Methods Existing ACs were randomized to either the control (SOC ACs) or intervention (Intervention ACs) arm. SoC ACs meet five times annually, receiving two-month ART refills with a four-month ART refill over year-end. Blood is drawn at the AC visit ahead of the clinical assessment visit. Intervention ACs meet twice annually receiving six-month ART refills, with a third individual visit for routine blood collection anytime two-four weeks before the annual clinical assessment AC visit. Primary outcomes will be retention in care, annual viral load assessment completion and viral load suppression. (<400copies/mL) after 2 years. Ethics approval has been granted by the University of Cape Town (HREC 652/2016) and the Medecins Sans Frontieres (MSF) Ethics Review Board (#1639). Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. Discussion Evaluation of an extended ART refill interval in adherence clubs will provide evidence towards novel model adaptions that can be made to further improve convenience for patients and leverage health system efficiencies. Trial registration Registered with the Pan African Clinical Trial Registry: PACTR201810631281009. Registered 11 September 2018.
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    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.
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    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.
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    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.
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    Correcting mortality for loss to follow-up: a nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa
    (Public Library of Science, 2011) Egger, Matthias; Spycher, Ben D; Sidle, John; Weigel, Ralf; Geng, Elvin H; Fox, Matthew P; MacPhail, Patrick; van Cutsem, Gilles; Messou, Eugène; Wood, Robin
    Background: The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART. Methods and Findings: We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year. Conclusions: The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up.
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    Early and late direct costs in a Southern African antiretroviral treatment programme: a retrospective cohort analysis
    (Public Library of Science, 2009) Leisegang, Rory; Cleary, Susan; Hislop, Michael; Davidse, Alistair; Regensberg, Leon; Little, Francesca; Maartens, Gary
    Gary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
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    Estimating loss to follow-up in HIV-infected patients on antiretroviral therapy: the effect of the competing risk of death in Zambia and Switzerland
    (Public Library of Science, 2011) Schöni-Affolter, Franziska; Keiser, Olivia; Mwango, Albert; Stringer, Jeffrey; Ledergerber, Bruno; Mulenga, Lloyd; Bucher, Heiner C; Westfall, Andrew O; Calmy, Alexandra; Boulle, Andrew; Chintu, Namwinga; Egger, Matthias; Chi, Benjamin H
    BACKGROUND: Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. Methods and FINDINGS: HIV-infected patients aged ≥18 years who started ART 2004-2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. CONCLUSIONS: In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings.
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    Growth of HIV-exposed uninfected infants in the first 6 months of life in South Africa: The IeDEA-SA collaboration
    (Public Library of Science, 2016) Morden, Erna; Technau, Karl-Günter; Giddy, Janet; Maxwell, Nicola; Keiser, Olivia; Davies, Mary-Ann
    BACKGROUND: HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa especially with the increasing coverage of more effective prevention of mother-to-child transmission (PMTCT) antiretroviral therapy regimens. This study describes the characteristics of South African HEU infants, investigates factors impacting birth weight and assesses their growth within the first 28 weeks of life. METHODS: This is a retrospective cohort based on routine clinical data from two South African PMTCT programmes. Data were collected between 2007 and 2013. Linear regression assessed factors affecting birth weight-for-age z-scores (WAZ) while growth (longitudinal WAZ) was assessed using mixed effects models. RESULTS: We assessed the growth of 2621 HEU infants (median birth WAZ was -0.65 (IQR -1.46; 0.0) and 51% were male). The feeding modalities practised were as follows: 0.5% exclusive breastfeeding, 7.9% breastfeeding with unknown exclusivity, 0.08% mixed breastfeeding and 89.2% formula feeding. Mothers with CD4 <200 cells/μl delivered infants with a lower birth WAZ (adjusted ß -0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with aCD4 ≥500 cells/μl. Similarly, mothers who did not receive antiretroviral drugs delivered infants with a lower birth WAZ (adjusted ß -0.39 [95% CI -0.67; -0.11], p = 0.007) compared to mothers who received antenatal antiretrovirals. Infants with a birth weight <2 500g (ß 0.070 [95% CI 0.061; 0.078], p <0.0001) experienced faster growth within the first 28 weeks of life compared to infants with a birth weight ≥2 500g. Infants with any breastfeeding exposure experienced slower longitudinal growth compared to formula fed infants (adjusted ß -0.012 [95% CI 0.021; -0.003], p = 0.011). CONCLUSION: Less severe maternal disease and the use of antiretrovirals positively impacts birth weight in this cohort of South African HEU infants. Formula feeding was common with breastfed infants experiencing marginally slower longitudinal growth.
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    Implementation of an electronic monitoring and evaluation system for the antiretroviral treatment programme in the Cape Winelands district, South Africa: a qualitative evaluation
    (Public Library of Science, 2015) Myburgh, Hanlie; Murphy, Joshua P; van Huyssteen, Mea; Foster, Nicola; Grobbelaar, Cornelius J; Struthers, Helen E; McIntyre, James A; Hurter, Theunis; Peters, Remco P H
    BACKGROUND: A pragmatic three-tiered approach to monitor the world's largest antiretroviral treatment (ART) programme was adopted by the South African National Department of Health in 2010. With the rapid expansion of the programme, the limitations of the paper-based register (tier 1) were the catalyst for implementation of the stand-alone electronic register (tier 2), which offers simple digitisation of the paper-based register. This article engages with theory on implementation to identify and contextualise enabling and constraining factors for implementation of the electronic register, to describe experiences and use of the register, and to make recommendations for implementation in similar settings where standardisation of ART monitoring and evaluation has not been achieved. METHODS: We conducted a qualitative evaluation of the roll-out of the register. This comprised twenty in-depth interviews with a diverse sample of stakeholders at facility, sub-district, and district levels of the health system. Facility-level participants were selected across five sub-districts, including one facility per sub-district. Responses were coded and analysed using a thematic approach. An implementation science framework guided interpretation of the data. Results & DISCUSSION: We identified the following seven themes: 1) ease of implementation, 2) perceived value of an electronic M&E system, 3) importance of stakeholder engagement, 4) influence of a data champion, 5) operational and logistical factors, 6) workload and role clarity, and 7) importance of integrating the electronic register with routine facility monitoring and evaluation. Interpreting our findings through an implementation theory enabled us to construct the scaffolding for implementation across the five facility-settings. This approach illustrated that implementation was not a linear process but occurred at two nodes: at the adoption of the register for roll-out, and at implementation at facility-level. CONCLUSION: In this study we found that relative advantage of an intervention and stakeholder engagement are critical to implementation. We suggest that without these aspects of implementation, formative and summative outcomes of implementation at both the adoption and coalface stages of implementation would be negatively affected.
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    Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection
    (Public Library of Science, 2016) Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn; Robles, Alex; Bayne, Madeleine; Garrity, Jetta; Rist, Michael; Rademeyer, Cecilia; Yoon, Hyejin; Lapedes, Alan; Gao, Hongmei; Greene, Kelli; Louder, Mark K; Kong, Rui; Karim, Salim Abdool; Burton, Dennis R; Barouch, Dan H; Nussenzweig, Michel C; Mascola, John R; Morris, Lynn; Montefiori, David C; Korber, Bette; Seaman, Michael S
    Author Summary In recent years, a new generation of monoclonal antibodies has been isolated from HIV-1 infected individuals that exhibit broad and potent neutralizing activity when tested against diverse strains of virus. There is a high level of interest in the field in determining if these antibodies can be used to prevent or treat HIV-1 infection. Because HIV-1 is adept at escaping from immune recognition, it is generally thought that combinations of multiple antibodies targeting different sites will be required for efficacy, much the same as seen for conventional antiretroviral drugs. How many and which antibodies to include in such combinations is not known. In this study, a new mathematical model was developed and used to accurately predict various measures of neutralizing activity for all possible combinations having a total of 2, 3, or 4 of the most promising antibodies. Through a systematic and comprehensive comparison, we identified optimal combinations of antibodies that best complement one another for enhanced anti-viral activity, and therefore may be most effective for the prevention or treatment of HIV-1 infection. These results provide important parameters that inform the selection of antibodies to develop for clinical use.
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    Pharmacokinetics, SAfety/tolerability, and EFficacy of high-dose RIFampicin in tuberculosis-HIV co-infected patients on efavirenz- or dolutegravir-based antiretroviral therapy: study protocol for an open-label, phase II clinical trial (SAEFRIF)
    (2020-02-13) Nabisere, Ruth; Musaazi, Joseph; Denti, Paolo; Aber, Florence; Lamorde, Mohammed; Dooley, Kelly E; Aarnoutse, Rob; Sloan, Derek J; Sekaggya-Wiltshire, Christine
    Abstract Background Tuberculosis (TB) is a significant public health problem that causes substantial morbidity and mortality. Current first-line anti-TB chemotherapy, although very effective, has limitations including long-treatment duration with a possibility of non-adherence, drug interactions, and toxicities. Dose escalation of rifampicin, an important drug within the regimen, has been proposed as a potential route to higher treatment efficacy with shorter duration and some studies have suggested that dose escalation is safe; however, these have almost entirely been conducted among human immunodeficiency (HIV)-negative TB patients. TB-HIV co-infected patients on antiretroviral therapy (ART) are at increased risk of drug-drug interactions and drug-related toxicities. This study aims to determine the safety of higher doses of rifampicin and its effect on the pharmacokinetics of efavirenz (EFV) and dolutegravir (DTG) in TB-HIV co-infected patients. Methods This study is a randomized, open-label, phase IIb clinical trial among TB-HIV infected adult outpatients attending an HIV clinic in Kampala, Uganda. Patients newly diagnosed with TB will be randomized to either standard-dose or high-dose rifampicin (35 mg/kg) alongside standard TB treatment. ART-naïve patients will be randomly assigned to first-line ART regimens (DTG or EFV). Those who are already on ART (DTG or EFV) at enrollment will be continued on the same ART regimen but with dose adjustment of DTG to twice daily dosing. Participants will be followed every 2 weeks with assessment for toxicities at each visit and measurement of drug concentrations at week 6. At the end of intensive-phase therapy (8 weeks), all participants will be initiated on continuation-phase treatment using standard-dose rifampicin and isoniazid. Discussion This study should avail us with evidence about the effect of higher doses of rifampicin on the pharmacokinetics of EFV and DTG among TB-HIV co-infected patients. The trial should also help us to understand safety concerns of high-dose rifampicin among this vulnerable cohort. Trial registration ClinicalTrials.gov, ID: NCT03982277. Registered retrospectively on 11 June 2019.
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    Protocol for a drugs exposure pregnancy registry for implementation in resource-limited settings
    (BioMed Central Ltd, 2012) Mehta, Ushma; Clerk, Christine; Allen, Elizabeth; Yore, Mackensie; Sevene, Esperanca; Singlovic, Jan; Petzold, Max; Mangiaterra, Viviana; Elefant, Elizabeth; Sullivan, Frank; Holmes, Lewis; Gomes, Melba
    BACKGROUND: The absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.METHODS/DESIGN:Sentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.DISCUSSION:In addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improve maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.
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    Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared
    (Public Library of Science, 2008) Keiser, Olivia; Orrell, Catherine; Egger, Matthias; Wood, Robin; Brinkhof, Martin W G; Furrer, Hansjakob; vCutsem, Gilles; Ledergerber, Bruno; Boulle, Andrew; (IeDEA-SA), for the Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases
    Comparing HIV treatment in Switzerland, where drug selection is individualized, and South Africa, where a programmatic approach is used, Matthias Egger and colleagues find similar virologic outcomes over two years.
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    South Africa's 'rollout' of highly active antiretroviral therapy: a critical assessment
    (2006) Nattrass, Nicoli
    The number of people on highly active antiretroviral therapy (HAART) in South Africa has risen from ,2000 in October 2003, to almost 200,000 by the end of 2005. Yet South Africa’s performance in terms of HAART coverage is poor both in comparison with other countries and the targets set by the government’s own Operational Plan. The public-sector HAART ‘‘rollout’’ has been uneven across South Africa’s nine provinces and the role of external assistance from NGOs and funding agencies such as the Global Fund and PEPFAR has been substantial. The National Treasury seems to have allocated sufficient funding to the Department of Health for a larger HAART rollout, but the Health Minister has not mobilized it accordingly. Failure to invest sufficiently in human resources— especially nurses—is likely to constrain the growth of HAART coverage.
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    Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction
    (Public Library of Science, 2013) de Waal, Reneé; Cohen, Karen; Maartens, Gary
    BACKGROUND: Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions. METHODS: We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. RESULTS: Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs) showed more limb fat loss (or less fat gain) with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs)); efavirenz (versus protease inhibitors (PIs)); and NRTI-containing (versus NRTI-sparing). RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. CONCLUSIONS: There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues) and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.
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    Trends in loss to follow-up among migrant workers on antiretroviral therapy in a community cohort in Lesotho
    (Public Library of Science, 2010) Bygrave, Helen; Kranzer, Katharina; Hilderbrand, Katherine; Whittall, Jonathan; Jouquet, Guillaume; Goemaere, Eric; Vlahakis, Nathalie; Triviño, Laura; Makakole, Lipontso; Ford, Nathan
    BACKGROUND: The provision of antiretroviral therapy (ART) to migrant populations raises particular challenges with respect to ensuring adequate treatment support, adherence, and retention in care. We assessed rates of loss to follow-up for migrant workers compared with non-migrant workers in a routine treatment programme in Morjia, Lesotho. Design All adult patients (≥18 years) initiating ART between January 1, 2008, and December 31, 2008, and followed up until the end of 2009, were included in the study. We described rates of loss to follow-up according to migrant status by Kaplan-Meier estimates, and used Poisson regression to model associations between migrant status and loss to follow-up controlling for potential confounders identified a priori. RESULTS: Our cohort comprised 1185 people, among whom 12% (148) were migrant workers. Among the migrant workers, median age was 36.1 (29.6-45.9) and the majority (55%) were male. We found no statistically significant differences between baseline characteristics and migrant status. Rates of lost to follow up were similar between migrants and non-migrants in the first 3 months but differences increased thereafter. Between 3 and 6 months after initiating antiretroviral therapy, migrants had a 2.78-fold increased rate of defaulting (95%CI 1.15-6.73); between 6 and 12 months the rate was 2.36 times greater (95%CI 1.18-4.73), whereas after 1 year the rate was 6.69 times greater (95%CI 3.18-14.09). CONCLUSIONS: Our study highlights the need for programme implementers to take into account the specific challenges that may influence continuity of antiretroviral treatment and care for migrant populations.
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    What is the optimal first line antiretroviral therapy in resource-limited settings?
    (Public Library of Science, 2012) Kenyon, Chris; Colebunders, Robert
    A perspective by Chris Kenyon and Robert Colebunders discusses policy implications for use of first line antiretroviral therapies in resource-limited settings, emerging from a new research study conducted by Campbell and colleagues.