Search

Background: Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART., Methods and Findings: Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness., Conclusions: ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality.

Background: Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa., Methods and Findings: Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77)., Conclusions: Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

Objectives: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow‐up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow‐up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. Methods: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow‐up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. Results: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow‐up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained‐other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained‐WC]). A high proportion of lost to follow‐up children, adolescents and young adults with HIV had self‐transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non‐informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. Conclusions: Our findings emphasise that lost to follow‐up is non‐ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow‐up, whereas linkage did not identify out‐of‐facility deaths, but showed that a large proportion of those reported as lost to follow‐up were self‐transfers. [ABSTRACT FROM AUTHOR]

Changes in an individual's contextual factors following HIV diagnosis may influence long-term outcomes. We evaluated how changes to contextual factors between HIV diagnosis and 9-month follow-up predict 5-year mortality among HIV-infected individuals in Durban, South Africa enrolled in the Sizanani Trial (NCT01188941). We used random survival forests to identify 9-month variables and changes from baseline predictive of time to mortality. We incorporated these into a Cox proportional hazards model including age, sex, and starting ART by 9 months a priori, 9-month social support and competing needs, and changes in mental health between baseline and 9 months. Among 1,154 participants with South African ID numbers, 900 (78%) had baseline and 9-month data available of whom 109 (12%) died after 9-month follow-up. Those who reported less social support at 9 months had a 16% higher risk of mortality. Participants who went without basic needs or healthcare at 9 months had a 2.6 times higher hazard of death compared to participants who did not. Low social support and competing needs at 9-month follow-up substantially increase long-term mortality risk. Reassessing contextual factors during follow-up and targeting interventions to increase social support and affordability of care may reduce long-term mortality for HIV-infected individuals in South Africa. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Early mortality in tuberculosis patients initially lost to follow up following diagnosis in provincial hospitals and primary health care facilities in Western Cape, South Africa." The correction addresses errors in the author contributions section of the article. The correct contributions are listed for each author. The authors involved in the study are Muhammad Osman, Sue-Ann Meehan, Arne von Delft, Karen Du Preez, Rory Dunbar, Florian M. Marx, Andrew Boulle, Alex Welte, Pren Naidoo, and Anneke C. Hesseling. [Extracted from the article]

Introduction: Few studies have systematically described population‐level differences comparing men and women across the continuum of routine HIV care. This study quantifies differentials in HIV care, treatment and mortality outcomes for men and women over time in South Africa. Methods: We analysed population‐wide linked anonymized data, including vital registration linkage, for the Western Cape Province, from the time of first CD4 count. Three antiretroviral therapy guideline eligibility periods were defined: 1 January 2008 to 31 July 2011 (CD4 cell count <200 cells/µL), 1 August 2011 to 31 December 2014 (<350 cells/µL), 1 January 2015 to 31 August 2016 (<500 cells/µL). We estimated care uptake based on service attendance, and modelled associations for men and women with ART initiation and overall, pre‐ART and ART mortality. Separate Cox proportional hazard models were built for each outcome and eligibility period, adjusted for tuberculosis, pregnancy, CD4 count and age. Results: Adult men made up 49% of the population and constituted 37% of those living with HIV. In 2009, 46% of men living with HIV attended health services, rising to 67% by 2015 compared to 54% and 77% of women respectively. Men contributed <35% of all CD4 cell counts over 10 years and presented with more advanced disease (39% of all first presentation CD4 cell counts from men were <200 cells/µL compared to 25% in women). ART access was lower in men compared to women (AHR 0.79 (0.77 to 0.80) summarized for Period 2) over the entire study). Mortality was greater in men irrespective of ART (AHR 1.08 (1.01 to 1.16) Period 3) and after ART start (AHR 1.15 (1.05 to 1.20) Period 3) with mortality differences decreasing over time. Conclusions: Compared to women, men presented with more advanced disease, were less likely to attend health care services annually, were less likely to initiate ART and had higher mortality overall and while receiving ART care. People living with HIV were more likely to initiate ART if they had acute reasons to access healthcare beyond HIV, such as being pregnant or being co‐infected with tuberculosis. Our findings point to missed opportunities for improving access to and outcomes from interventions for men along the entire HIV cascade. [ABSTRACT FROM AUTHOR]

Background Bedaquiline is used as a substitute for second-line injectable (SLI) intolerance in the treatment of multidrug-resistant (MDR) tuberculosis, but the efficacy and safety of this strategy is unknown. Methods In this retrospective cohort study adults receiving bedaquiline substitution for MDR tuberculosis therapy, plus a matched control group who did not receive bedaquiline, were identified from the electronic tuberculosis register in the Western Cape Province, South Africa. The primary outcome measure was the proportion of patients with death, loss to follow-up, or failure to achieve sustained culture conversion at 12 months of treatment. Results Data from 162 patients who received bedaquiline substitution and 168 controls were analyzed; 70.6% were infected with human immunodeficiency virus. Unfavorable outcomes occurred in 35 of 146 (23.9%) patients in the bedaquiline group versus 51 of 141 (36.2%) in the control group (relative risk, 0.66; 95% confidence interval,.46 –.95). The number of patients with culture reversion was lower in those receiving bedaquiline (1 patient; 0.8%) than in controls (12 patients; 10.3%; P =.001). Delayed initiation of bedaquiline was independently associated with failure to achieve sustained culture conversion (adjusted odds ratio for every 30-day delay, 1.5; 95% confidence interval, 1.1–1.9). Mortality rates were similar at 12 months (11 deaths in each group; P =.97). Conclusions Substituting bedaquiline for SLIs in MDR tuberculosis treatment resulted in improved outcomes at 12 months compared with patients who continued taking SLIs, supporting the use of bedaquiline for MDR tuberculosis treatment in programmatic settings. [ABSTRACT FROM AUTHOR]

Introduction: South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV-positive South Africans. To ensure that further expansion of services does not compromise quality of care, long-term outcomes must be monitored. Few studies have reported long-term mortality in resource-constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long-term mortality and viral suppression among adults starting ART in South Africa. Methods: The study was a cohort analysis of routine data on adults with IDs starting ART 2004-2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan-Meier estimator and Cox's proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV-negative. Viral suppression in patients with viral loads (VLs) in their last year of followup was the secondary outcome. Results: Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02- 3.14)/100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007-2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIVnegative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV-negative population, and SMRs were similar for all baseline CD4 strata. Three-quarters of patients had VLs in their last year, and 86% of these were virally suppressed. Conclusions: The South African ART programme has shown a remarkable ability to initiate and manage patients successfully over 12 years, despite rapid expansion. With further scale-up, testing and initiating men on ART must be a national priority. [ABSTRACT FROM AUTHOR]

Background. Morbidity and mortality remain high among hospitalized patients infected with human immunodeficiency virus (HIV) in sub-Saharan Africa despite widespread availability of antiretroviral therapy. Severe anemia is likely one important driver, and some evidence suggests that blood transfusions may accelerate HIV progression and paradoxically increase short-term mortality. We investigated the relationship between anemia, blood transfusions, and mortality in a South African district hospital. Methods. Unselected consecutive HIV-infected adults requiring acute medical admission to a Cape Town township district hospital were recruited. Admission hemoglobin concentrations were used to classify anemia severity according to World Health Organization/AIDS Clinical Trials Group criteria. Vital status was determined at 90 days, and Cox regression analyses were used to determine independent predictors of mortality. Results. Of 585 HIV-infected patients enrolled, 578 (98.8%) were included in the analysis. Anemia was detected in 84.8% of patients and was severe (hemoglobin, 6.5-7.9 g/dL) or life-threatening (hemoglobin, <6.5 g/dL) in 17.3% and 13.3%, respectively. Within 90 days of the date of admission, 13.5% (n = 78) patients received at least 1 blood transfusion with red cell concentrate and 77 (13.3%) patients died. In univariable analysis, baseline hemoglobin and receipt of blood transfusion were associated with increased mortality risk. However, in multivariable analysis, neither hemoglobin nor receipt of a blood transfusion were independently associated with greater mortality risk. Acquired immune deficiency syndrome-defining illnesses other than tuberculosis and impaired renal function independently predicted mortality. Conclusions. Newly admitted HIV-infected adults had a high prevalence of severe or life-threatening anemia and blood transfusions were frequently required. However, after adjustment for confounders, blood transfusions did not confer an increased mortality risk. [ABSTRACT FROM AUTHOR]

: Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North America by 4 years after starting antiretroviral therapy. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low-and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. Methods and Findings: Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was $200 cells/ml, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was ,50 cells/ml. Life expectancies of patients with baseline CD4 counts $200 cells/ml were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations. Conclusions: South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/ml. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART. Methodology/Principal Findings: We retrospectively reviewed TB registers and clinical notes of 209 TB/HIV co-infected adults with a CD4 count <250 cells/µl and registered for TB treatment at one primary care clinic in a South African township between June 2008 and May 2009. Using Kaplan-Meier and Cox proportional hazard analysis, we compared time between initiation of TB treatment and ART for the periods before and after full, "one-stop shop" integration of TB and HIV services (in December 2009). Potential confounders were determined a priori through directed acyclic graphs. Robustness of assumptions was investigated by sensitivity analyses. The analysis included 188 patients (100 pre- and 88 post-integration), yielding 56 person-years of observation. Baseline characteristics of the two groups were similar. Median time to ART initiation decreased from 147 days (95% confidence interval [CI] 85-188) before integration of services to 75 days (95% CI 52=119) post-integration. In adjusted analyses, patients attending the clinic post-integration were 1.60 times (95% CI 1.11-2.29) more likely to have started ART relative to the pre-integration period. Sensitivity analyses supported these findings. Conclusions/Significance: Full TB/HIV care integration is feasible and led to a 60% increased chance of co-infected patients starting ART, while reducing time to ART initiation by an average of 72 days. Although these estimates should be confirmed through larger studies, they suggest that scale-up of full TB/HIV service integration in high TB/HIV prevalence settings may shorten time to ART initiation, which might reduce excess mortality and morbidity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Loss to follow-up (LTF) challenges the reporting of antiretroviral treatment (ART) programmes, since it encompasses patients alive but lost to programme and deaths misclassified as LTF. We describe LTF before and after correction for mortality in a primary care ART programme with linkages to the national vital registration system. Methods and Findings: We included 6411 patients enrolled on ART between March 2001 and June 2007. Patients LTF with available civil identification numbers were matched with the national vital registration system to ascertain vital status. Corrected mortality and true LTF were determined by weighting these patients to represent all patients LTF. We used Kaplan-Meier estimates and Cox regression to describe LTF, mortality among those LTF, and true LTF. Of 627 patients LTF, 85 (28.8%) had died within 3 months after their last clinic visits. Respective estimates of LTF before and after correction for mortality were 6.9% (95% confidence interval [CI] 6.2-7.6) and 4.3% (95% CI 3.5-5.3) at one year on ART, and 23.9% (95% CI 21.0-27.2) and 19.7% (95% CI 16.1-23.7) at 5 years. After correction for mortality, the hazard of LTF was reversed from decreasing to increasing with time on ART. Younger age, higher baseline CD4 count, pregnancy and increasing calendar year were associated with higher true LTF. Mortality of patients LTF at 1, 12 and 24 months after their last visits was respectively 23.1%, 30.9% and 43.8%; 78.0% of deaths occurred during the first 3 months after last visit and 45.0% in patients on ART for 0 to 3 months. Conclusions: Mortality of patients LTF was high and occurred early after last clinic visit, especially in patients recently started on ART. Correction for these misclassified deaths revealed that the risk of true LTF increased over time. Research targeting groups at higher risk of LTF (youth, pregnant women and patients with higher CD4 counts) is needed. [ABSTRACT FROM AUTHOR]

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/mL, 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. [ABSTRACT FROM AUTHOR]

Background: The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity. Methodology/Principal Findings: Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 personyears. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of motherto- child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality. Conclusions: The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. Methods: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. Results: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-tofollow- up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality. Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. Conclusions: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential. [ABSTRACT FROM AUTHOR]

Knowledge of the experience and outcomes of current paediatric antiretroviral treatment (ART) programmes in sub-Saharan Africa can inform new programmes in the region as well as enhance existing ones. This is urgently needed to facilitate the scale-up of treatment, which is needed to address the burden of paediatric HIV cases on the continent. We reviewed the characteristics and outcomes of programmes with clinical paediatric ART studies published prior to 1 January 2008. The outcomes of the studies were comparable to similar ones from developed countries; however, the duration of follow-up was relatively limited in almost all the studies reviewed. One-year survival probability was between 84% and 91%, and considerable improvement in the clinical, immunologic and viral status of the paediatric patients was generally recorded. Loss to follow-up was less than 10% in all but two studies. Adherence to treatment was good and few adverse events were reported. This is despite the fact that many programmes were subject to enormous constraints in terms of health services, and despite widespread use of adult fixed-dose combinations for paediatric patients, including young infants. While the majority of children commencing ART were severely ill, most children were old (median age >5 years for almost all studies) with relatively few infants and young children (age <2 years) receiving treatment. This is in contrast to knowledge of rapid disease progression in the majority of HIV-infected infants and despite the World Health Organization's recent recommendations to commence ART in all HIV-infected infants less than one year old. There is an urgent need to address barriers to ART for infants. Studies of the outcomes of programmes treating infants as well as those with longer-term follow-up are also needed. [ABSTRACT FROM AUTHOR]

The article discusses the risk of tuberculosis in children which resulted from advancing human immunodeficiency virus (HIV) infection, which is a major contributor to morbidity and mortality associated with HIV. The author states that as of December 2009, this situation is very common in Africa where the risk of tuberculosis is high. Anti-retroviral therapy (ART), which is used to allow recovery of immune function and to reduce the risk of tuberculosis in patients with HIV, is mentioned.

Little is known about outcomes after transfer out (TFO) and loss to follow-up (LTF) and how differential outcomes might bias mortality estimates, as analyses generally censor or exclude TFOs/LTF. Using data linked to the National Population Register, we explored mortality among TFO and LTF patients compared with patients who were retained and investigated how linkage impacted on mortality estimates.A cohort analysis of routine data on adults with civil identification numbers starting antiretroviral therapy (ART) 2004-2009 in 4 large South African ART cohorts. The number, proportion, timing, and mortality of TFOs and LTF were reported. Mortality was compared using Kaplan-Meier curves, Cox's proportional hazards, and competing risks regression.Before linkage, 1207 patients (6%) had died, 2624 (13%) were LTF, 1067 (5%) were TFO and 14,583 (75%) were retained. Compared with retained, mortality risk was 3 times higher among TFO patients [adjusted hazard ratio (aHR), 3.11; 95% confidence interval (CI): 2.42 to 3.99] and 20 times higher among LTF patients (aHR, 22.03; 95% CI: 20.05 to 24.21). Excluding early deaths after TFO or LTF, the risk was comparable among TFOs and retained (aHR, 0.75; 95% CI: 0.54 to 1.03) and higher among LTF (aHR, 2.85; 95% CI: 2.43 to 3.33). After linkage, corrected mortality was higher than site-reported mortality. Censoring did not, however, lead to substantial underestimation of mortality among TFOs.Although TFO and LTF predicted mortality, the lower incidence of TFO and subsequent death compared with LTF meant that censoring TFOs did not bias mortality estimates. Future cohort analyses should explicitly consider proportions of TFO/LTF and mortality event rates. [ABSTRACT FROM AUTHOR]

In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information.We analyzed data from a large multicohort study in South Africa, where HIV RNA is routinely monitored. Adult HIV-positive patients initiating cART between 2003 and 2010 were included. Mortality was analyzed in Cox models; CD4 count slope by HIV RNA level was assessed using linear mixed models.About 44,829 patients (median age: 35 years, 58% female, median CD4 count at cART initiation: 116 cells/mm3) were followed up for a median of 1.9 years, with 3706 deaths. Mean CD4 count slopes per week ranged from 1.4 [95% confidence interval (CI): 1.2 to 1.6] cells per cubic millimeter when HIV RNA was <400 copies per milliliter to -0.32 (95% CI: -0.47 to -0.18) cells per cubic millimeter with >100,000 copies per milliliter. The association of CD4 slope with mortality depended on current CD4 count: the adjusted hazard ratio (aHRs) comparing a >25% increase over 6 months with a >25% decrease was 0.68 (95% CI: 0.58 to 0.79) at <100 cells per cubic millimeter but 1.11 (95% CI: 0.78 to 1.58) at 201-350 cells per cubic millimeter. In contrast, the aHR for current CD4 count, comparing >350 with <100 cells per cubic millimeter, was 0.10 (95% CI: 0.05 to 0.20).Absolute CD4 count remains a strong risk for mortality with a stable effect size over the first 4 years of cART. However, CD4 count slope and HIV RNA provide independently added to the model. [ABSTRACT FROM AUTHOR]

The article presents a research which aims to examine the effects on mortality, viral suppression, and other health outcomes of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) program. The STRETCH program provides educational training of nurses to initiate and represcribe antiretroviral therapy (ART). The method undertook cluster-randomized trial in South Africa and it is implicated that role of primary-care nurses in ART initiation can improve health outcomes. INSET: Panel: Research in context.

Tenofovir (TDF) is increasingly used in second-line antiretroviral treatment (ART) in sub-Saharan Africa. We compared outcomes of second-line ART containing and not containing TDF in cohort studies from Zambia and the Republic of South Africa (RSA).Patients aged 16 years and older starting protease-inhibitor-based second-line ART in Zambia (1 cohort) and RSA (5 cohorts) were included. We compared mortality, immunological failure (all cohorts), and virological failure (RSA only) between patients receiving and not receiving TDF. Competing risk models and Cox models adjusted for age, sex, CD4 count, time on first-line ART, and calendar year were used to analyze mortality and treatment failure, respectively. Hazard ratios (HRs) were combined in fixed-effects meta-analysis.1687 patients from Zambia and 1556 patients from RSA, including 1350 (80.0%) and 206 (13.2%) patients starting TDF, were followed over 4471 person-years. Patients on TDF were more likely to have started second-line ART in recent years and had slightly higher baseline CD4 counts than patients not on TDF. Overall, 127 patients died, 532 were lost to follow-up, and 240 patients developed immunological failure. In RSA, 94 patients had virologic failure. Combined HRs comparing TDF with other regimens were 0.60 (95% confidence interval [CI]: 0.41 to 0.87) for immunologic failure and 0.63 (0.38-1.05) for mortality. The HR for virologic failure in RSA was 0.28 (0.09-0.90).In this observational study, patients on TDF-containing second-line ART were less likely to develop treatment failure than patients on other regimens. TDF seems to be an effective component of second-line ART in southern Africa. [ABSTRACT FROM AUTHOR]