Gender differences in presentation and early survival in an antiretroviral therapy programme in Gugulethu : South Africa, 2002-2007

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=001). 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, 0.93-1.50). There was evidence of mediation by degree of disease. In the preHAART period, the Sobel test found significant associations between mortality and CD4 count (p=0.044) as well as WHO stage (p=0.003). On HAART, too, CD4 count (p=0.045) and WHO stage (p< 0.001) appeared to mediate the effect of gender on death. Similarly, in the total cohort, there was evidence to support mediation by CD4 count (p=0.035) and WHO stage (p<0.001). There was a crude association between male gender and the risk of being L TFU (HR for L TFU during the total study period comparing males to females, 1.26, 95% CI, 0.89-1.78 ; p=0.194). This was strengthened by adjustment for age and monthly income (HR,1.35, 95% CI, 0.92-1.97). In this cohort, men appeared to have worse survival prospects than women due to more advanced HIV disease on programme entry. Previous studies have attributed the disproportionate access of women to HAART to gender differences in health seeking behaviour. This study argues that the prime obstacle might be the existing orientation of primary health care systems in developing countries towards the needs of women more than those of men. It suggests that women have better access to primary health services through the existing focus on maternal and child health. Women who are diagnosed and referred for HAART through these services are generally younger and healthier than men, who are diagnosed through services for tuberculosis (TB) and sexually transmitted infections (STis). This might explain why fewer men than women access HAART, and why they are diagnosed at later stages of disease progression. As a result, men may be disadvantaged in access to HAAR T in South Africa. The study suggests a number of short- and long-term solutions including : further research on obstacles to male access to HAART; changes in national policy; and the establishment of male-friendly services as an entry point for men into broader health services. Such approaches might facilitate the earlier diagnosis and treatment of men and improve their survival in HAART programmes

The evolution and effectiveness of the South African antiretroviral therapy program

Includes bibliographical referencesAlthough 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 individual level 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 person years. 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 area challenge

Feeding practices and nutritional status of HIV-exposed and HIV-unexposed infants in the Western Cape

Background: Optimal infant- and young child–feeding practices are crucial for nutritional status, growth, development, health and, ultimately, survival. Human breast milk is optimal nutrition for all infants. Complementary food introduced at the correct age is part of optimal feeding practices. In South Africa, widespread access to antiretrovirals and a programme to prevent mother-to-child transmission of HIV have reduced HIV infection in infants and increased the number of HIV-exposed uninfected (HEU) infants. However, little is known about the feeding practices and nutritional status of HEU and HIV-unexposed (HU) infants.Objective: To assess the feeding practices and nutritional status of HIV-exposed and HIV-unexposed (HU) infants in the Western Cape.Design: Prospective substudy on feeding practices nested in a pilot study  investigating the innate immune abnormalities in HEU infants compared to HU infants. The main study commenced at week 2 of life with the nutrition component added from 6 months. Information on children’s dietary intake was obtained at each visit from the caregiver, mainly the mother. Head circumference, weight and length were recorded at each visit. Data were obtained from 6-, 12- and 18-month visits. World Health Organization feeding practice indicators and nutrition indicators were utilised.Setting: Tygerberg Academic Hospital, Western Cape. Mothers were recruited from the postnatal wards.Subjects: Forty-seven mother–infant pairs, 25 HEU and 22 HU infants, participated in this nutritional substudy. Eight (17%) infants, one HU and seven HEU, were lost to follow-up over the next 12 months. The HEU children were mainly Xhosa (76%) and HU were mainly mixed race (77%).Results: The participants were from poor socio-economic backgrounds. In both groups, adherence to breastfeeding recommendations was low with suboptimal dietary diversity. We noted a high rate of sugar- and salt-containing snacks given from a young age. The HU group had poorer anthropometric and nutritional indicators not explained by nutritional factors alone. However, alcohol and tobacco use was much higher amongst the HU mothers.Conclusion: Adherence to breastfeeding recommendations was low. Ethnicity and cultural milieu may have influenced feeding choices and growth. Further research is needed to understand possible reasons for the poorer nutritional and anthropometric indicators in the HU group

Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting

Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study

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

Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study.

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

Cervical precancer and cancer incidence among insured women with and without HIV in South Africa.

HIV infection increases the risk of developing cervical cancer; however, longitudinal studies in sub-Saharan Africa comparing cervical cancer rates between women living with HIV (WLWH) and women without HIV are scarce. To address this gap, we compared cervical precancer and cancer incidence rates between WLWH and women without HIV in South Africa using reimbursement claims data from a medical insurance scheme from January 2011 to June 2020. We used Royston-Parmar flexible parametric survival models to estimate cervical precancer and cancer incidence rates as a continuous function of age, stratified by HIV status. Our study population consisted of 518 048 women, with exclusions based on the endpoint of interest. To analyse cervical cancer incidence, we included 517 312 women, of whom 564 developed cervical cancer. WLWH had an ~3-fold higher risk of developing cervical precancer and cancer than women without HIV (adjusted hazard ratio for cervical cancer: 2.99; 95% confidence interval [CI]: 2.40-3.73). For all endpoints of interest, the estimated incidence rates were higher in WLWH than women without HIV. Cervical cancer rates among WLWH increased at early ages and peaked at 49 years (122/100 000 person-years; 95% CI: 100-147), whereas, in women without HIV, incidence rates peaked at 56 years (40/100 000 person-years; 95% CI: 36-45). Cervical precancer rates peaked in women in their 30s. Analyses of age-specific cervical cancer rates by HIV status are essential to inform the design of targeted cervical cancer prevention policies in Southern Africa and other regions with a double burden of HIV and cervical cancer

Life years lost associated with mental illness: A cohort study of beneficiaries of a South African medical insurance scheme.

BACKGROUND People with mental illness have a reduced life expectancy, but the extent of the mortality gap and the contribution of natural and unnatural causes to excess mortality among people with mental illness in South Africa are unknown. METHODS We analysed reimbursement claims from South African medical insurance scheme beneficiaries aged 15-85 years. We estimated excess life years lost (LYL) associated with organic, substance use, psychotic, mood, anxiety, eating, personality, developmental or any mental disorders. RESULTS We followed 1,070,183 beneficiaries for a median of three years, of whom 282,926 (26.4 %) received mental health diagnoses. Men with a mental health diagnosis lost 3.83 life years (95 % CI 3.58-4.10) compared to men without. Women with a mental health diagnosis lost 2.19 life years (1.97-2.41) compared to women without. Excess mortality varied by sex and diagnosis, from 11.50 LYL (95 % CI 9.79-13.07) among men with alcohol use disorder to 0.87 LYL (0.40-1.43) among women with generalised anxiety disorder. Most LYL were attributable to natural causes (men: 3.42, women: 1.94). A considerable number of LYL were attributable to unnatural causes among men with bipolar (1.52) or substance use (2.45) disorder. LIMITATIONS Mental diagnoses are based on reimbursement claims. CONCLUSIONS Premature mortality among South African individuals with mental disorders is high. Our findings support interventions for the prevention, early detection, and treatment of physical comorbidities in this population. Targeted programs for suicide prevention and substance use treatment, particularly among men, can help reduce excess mortality from unnatural causes

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time-series analysis.

AIMS The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. METHODS We conducted an interrupted time-series analysis using insurance claims from 1 January 2017 to 1 June 2020 of beneficiaries 18 years or older from a large private sector medical insurance scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until 1 June 2020. RESULTS 710 367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% confidence interval (CI) 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the introduction of the lockdown and did not recover to pre-lockdown levels by 1 June 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24). CONCLUSIONS Mental health care utilisation rates for inpatient and outpatient services decreased substantially after the introduction of the lockdown. Hospital admissions and outpatient consultations for alcohol withdrawal syndrome increased after the introduction of the lockdown, but statistical uncertainty precludes strong conclusions about a potential unintended effect of the alcohol sales ban. Governments should integrate strategies for ensuring access and continuity of essential mental health services during lockdowns in pandemic preparedness planning

Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level