Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study (original) (raw)
Related papers
Twelve-year mortality in adults initiating antiretroviral therapy in South Africa
Journal of the International AIDS Society
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.
2008
• By 2005, an estimated 500 000 people with HIV had initiated highly active antiretroviral therapy (HAART) in sub-Saharan Africa. However, disproportionately more women than men have accessed HAART in most developing countries including South Africa. While there has been considerable recent interest in the determinants of mortality among patients receiving HAART in developing countries, there is conflicting evidence about gender differences and survival in HAAR T programmes. This study explored whether there were gender differences in early mortality among 2 843 treatment-naive men and women entering care in a large South African HAART programme. The study was a secondary analysis of patient records covering three time periods: person-time from programme entry to the initiation ofHAART; person-time from HAART initiation to one year on treatment; and the total person-time from programme entry to one year on HAART. Cox' s proportional hazards regression •was used to investigate crude and adjusted associations between basehne characteristics and mortality as we11 as loss-to-follow-up (LTFU). Using the Sobel test, the study explored whether the degree of disease (according to CD4 count and WHO stage) played a mediating role in any association between gender and mortality. In all three time periods, the analysis found a strong crude associ~tiol). between male gender and mortality. Prior to HAART-initiation, there was a 31 % increase in the risk of mortality (crude Hazard Ratio (HR) 1.31, 95% CI, 0.93-1.86; p=0.131). In the period on HAART, this association strengthened (crude HR 1.57, 95% CI, 1.14-2.16; p=0.005). Overall, male gender increased the risk of mortality in the total cohort by 49% (crude HR, 1.49, 95% CI, 1.17-1.88; p=OOl). Adjustment for baseline characteristics, including CD4 count and WHO stage, attenuated these crude associations. After adjustment, there was no increase in risk associated with male gender in the period pre-HAART (HR 1.01, 95% CI, 0.67-1.51). On HAART, there was a 19% increase in risk (HR 1.19, 95% CI, 0.88-1.67). In the total cohort, this was slightly attenuated (HR 1.15, 95% CI, TABLE OF CONTENTS 1
Journal of the International AIDS Society, 2011
Background: Because men in Africa are less likely to access HIV/AIDS care than women, we aimed to determine if men have differing outcomes from women across a nationally representative sample of adult patients receiving combination antiretroviral therapy in Uganda. Methods: We estimated survival distributions for adult male and female patients using Kaplan-Meier, and constructed multivariable regressions to model associations of baseline variables with mortality. We assessed person-years of life lost up to age 55 by sex. To minimize the impact of patient attrition, we assumed a weighted 30% mortality rate among those lost to follow up. Results: We included data from 22,315 adults receiving antiretroviral therapy. At baseline, men tended to be older, had lower CD4 baseline values, more advanced disease, had pulmonary tuberculosis and had received less treatment follow up (all at p < 0.001). Loss to follow up differed between men and women (7.5 versus 5.9%, p < 0.001). Over the period of study, men had a significantly increased risk of death compared with female patients (adjusted hazard ratio 1.43, 95% CI 1.31-1.57, p < 0.001). The crude mortality rate for males differed importantly from females (43.9, 95% CI 40.7-47.0/1000 person-years versus 26.9, 95% CI 25.4-28.5/1000 person years, p < 0.001). The probability of survival was 91.2% among males and 94.1% among females at 12 months. Person-years of life lost was lower for females than males (689.7 versus 995.9 per 1000 person-years, respectively). Conclusions: In order to maximize the benefits of antiretroviral therapy, treatment programmes need to be gender sensitive to the specific needs of both women and men. Particular efforts are needed to enroll men earlier into care.
The evolution and effectiveness of the South African antiretroviral therapy program
2014
Although South Africa has the largest antiretroviral therapy (ART) program worldwide, data on key outcomes like mortality and loss to follow-up (LTF) are limited. A few cohorts have published patient outcomes but there is no national reporting on ART scale-up and its impact on the health of HIV-infected individuals. Yet such monitoring of outcomes is vital to inform and improve service delivery. The International epidemiologic Databases to Evaluate AIDS Southern Africa collaboration (IeDEA-SA) was established in 2005 to collect and analyze individuallevel data from the larger cohorts of individuals on ART in Southern Africa. Using routine, anonymized data from the South African sites, this thesis aims to describe how the program has evolved over 10 years and to assess its effectiveness. Five quantitative analyses were performed using descriptive statistics and survival analysis methods. The studies used patient-level data on adult patients starting ART to describe characteristics and to explore outcomes and temporal changes in outcomes over time. Patient numbers ranged from 19,481 (limited to cohorts with civil identification numbers) to 83,576 adults, followed for up to 214,400 personyears. The results are presented as four published papers and one submitted for publication. The thesis describes a rapid, massive scale-up of services. Despite improvements in baseline immunologic status, late diagnosis and ART initiation especially in men are a challenge. Over five years, 12-month mortality drops and 12-month LTF increases, suggesting that LTF is a greater challenge to program effectiveness than mortality. Excluding early deaths after TFO/LTF, mortality risk compared with retained patients is similar among TFOs and higher among LTF. Censoring TFOs did not bias mortality estimates due to the lower incidence of TFO and subsequent death compared with LTF. Mortality increases with age at ART initiation, but the effect of age is modified by baseline immunologic status. The proportions of patients ≥50 years old enrolling and remaining in care each year increases. Men have higher mortality on ART than women and this is only partly explained by more advanced HIV disease at ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. Observed gender differences in mortality on ART may be best explained by background differences in mortality between men and women unrelated to HIV/AIDS or ART. The thesis concludes that the major challenges to program effectiveness are programmatic and not clinical. They include the earlier initiation of patients, especially men and patients ≥50 years old, and the need for good monitoring systems and strategies to retain patients in lifelong chronic care.
PLoS Medicine, 2013
Background: Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in lowand 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 HIVpositive 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 200cells/ml,comparedto29.5y(95200 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 200cells/ml,comparedto29.5y(95200 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.
High mortality rates in men initiated on anti-retroviral treatment in KwaZulu-Natal, South Africa
PloS one, 2017
In attaining UNAIDS targets of 90-90-90 to achieve epidemic control, understanding who the current utilizers of HIV treatment services are will inform efforts aimed at reaching those not being reached. A retrospective chart review of CAPRISA AIDS Treatment Program (CAT) patients between 2004 and 2013 was undertaken. Of the 4043 HIV-infected patients initiated on ART, 2586 (64.0%) were women. At ART initiation, men, compared to women, had significantly lower median CD4+ cell counts (113 vs 131 cells/mm3, p <0.001), lower median body mass index (BMI) (21.0 vs 24.2 kg/m2, p<0.001), higher mean log viral load (5.0 vs 4.9 copies/ml, p<0.001) and were significantly older (median age: 35 vs. 32 years, p<0.001). Men had higher mortality rates compared to women, 6.7 per 100 person-years (p-y), (95% CI: 5.8-7.8) vs. 4.4 per 100 p-y, (95% CI: 3.8-5.0); mortality rate ratio: 1.54, (95% CI: 1.27-1.87), p <0.001. Age-standardised mortality rate was 7.9 per 100 p-y (95% CI: 4.1-11.7...
Andrew Boulle1, Landon Myer1 for the International Epidemiologic Databases to Evaluate AIDS
2016
Background: Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART. Methods and Findings: Analyses included 46,201 ART-naı̈ve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached.200 cells/ml. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised
South African Medical Journal, 2019
This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0. Background. South Africa (SA) has one of the largest HIV/AIDS epidemics in the world and the most extensive antiretroviral therapy (ART) programme globally, which was rolled out from 2004. This paper reports the trends in HIV/AIDS mortality pre and post ART rollout in SA. Methods. Vital registration cause-of-death data from Statistics South Africa were adjusted for under-reporting of deaths using demographic methods. Misattributed HIV/AIDS deaths were identified by regressing excess mortality on a lagged indicator HIV antenatal clinic prevalence for causes found to be associated with HIV/AIDS. Background trends in the source-cause mortality rates were estimated from the trend in cause-specific mortality experienced among 75-84-year-olds. Mortality rates were calculated using midyear population estimates and the World Health Organization world standard age-weights. Results. We estimated over 3 189 000 HIV/AIDS deaths for 1997-2012. In 1997, 60 336 (14.5%) of deaths were attributed to HIV/AIDS; this number peaked in 2006 at 283 564 (41.9%) and decreased to 153 661 (29.1%) by 2012; female mortality rates peaked in 2005 and those of males in 2006. Men aged 35 years and older had higher mortality rates than did women. While the rates at ages below 65 years in 2012 were lower than those in 2006, rates of those age 65 years and older remained unchanged. Conclusion. The number of HIV/AIDS deaths has almost halved since the ART rollout. Of concern is the high mortality in men 45 years and older and the high mortality of men compared with women in the older ages by 2012; this gap has increased with age. Treatment and prevention programmes should strategise how to target men.