The tuberculosis challenge in a rural South African HIV programme.

BACKGROUND: South Africa remains the country with the greatest burden of HIV-infected individuals and the second highest estimated TB incidence per capita worldwide. Within South Africa, KwaZulu-Natal has one of the highest rates of TB incidence and an emerging epidemic of drug-resistant tuberculosis. METHODS: Review of records of consecutive HIV-infected people initiated onto ART between 1st January 2005 and 31st March 2006. Patients were screened for TB at initiation and incident episodes recorded. CD4 counts, viral loads and follow-up status were recorded; data was censored on 5th August 2008. Geographic cluster analysis was performed using spatial scanning. RESULTS: 801 patients were initiated. TB prevalence was 25.3%, associated with lower CD4 (AHR 2.61 p = 0.01 for CD4 25 copies/ml (OR 1.75 p = 0.11). A low-risk cluster for incident TB was identified for patients living near the local hospital in the geospatial analysis. CONCLUSION: There is a large burden of TB in this population. Rate of incident TB stabilises at a rate higher than that of the overall population. These data highlight the need for greater research on strategies for active case finding in rural settings and the need to focus on strengthening primary health care

An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa

BackgroundDespite the severe impact of HIV in sub-Saharan Africa, the health of older people aged 50+ is often overlooked owing to the dearth of data on the direct and indirect effects of HIV on older people's health status and well-being. The aim of this study was to examine correlates of health and well-being of HIV-infected older people relative to HIV-affected people in rural South Africa, defined as participants with an HIV-infected or death of an adult child due to HIV-related cause. MethodsData were collected within the Africa Centre surveillance area using instruments adapted from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample of 422 people aged 50+ participated. We compared the health correlates of HIV-infected to HIV-affected participants using ordered logistic regressions. Health status was measured using three instruments: disability index, quality of life and composite health score. ResultsMedian age of the sample was 60 years (range 50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than men to be in good functional ability. Women's adjusted odds of being in good overall health state were similarly lower than men's; while income and household wealth status were stronger correlates of quality of life. HIV-infected participants reported better functional ability, quality of life and overall health state than HIV-affected participants. Discussion and Conclusions The enhanced healthcare received as part of anti-retroviral treatment as well as the considerable resources devoted to HIV care appear to benefit the overall well-being of HIV-infected older people; whereas similar resources have not been devoted to the general health needs of HIV uninfected older people. Given increasing numbers of older people, policy and programme interventions are urgently needed to holistically meet the health and well-being needs of older people beyond the HIV-related care system. <br/

Association of Age with Mortality and Virological and Immunological Response to Antiretroviral Therapy in Rural South African Adults

OBJECTIVE: To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort. DESIGN: Retrospective cohort analysis using data from a public HIV Treatment & Care Programme. METHODS: Adults initiating ART 1(st) August 2004-31(st) October 2009 were stratified by age at initiation: young adults (16-24 years) mid-age adults (25-49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points. RESULTS: 8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25-49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90-7.78); 6.55 (95% CI 6.11-7.02) and 8.69 (95% CI 7.34-10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0-3 months (MR: 27.1 vs 17.17 and 21.36) and 3-12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1 year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0-3 months) whilst immunological and virological responses were associated with mortality after 12 months. CONCLUSIONS: Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART

Poor long-term outcomes for cryptococcal meningitis in rural South Africa.

OBJECTIVES: To explore linkage to and retention in HIV care after an episode of cryptococcal meningitis (CM) in rural South Africa. Design. A retrospective case series of adult individuals (> or = 16 years old) with laboratory-confirmed CM from January - December 2007 at Hlabisa Hospital--a district hospital in northern KwaZulu-Natal. OUTCOME MEASURES: Inpatient mortality and associated risk factors were analysed. The proportion alive and on antiretroviral therapy (ART) at 2 years was determined by linkage to the HIV treatment programme. RESULTS: One hundred and four individuals were identified with laboratory diagnosis of CM; 74/104 (71.2%) with complete records were included in the analysis. Inpatient mortality was high (40.5%) and was significantly associated with reduced conscious level (aHR 3.09, 95% CI 1.30 - 7.33) and absence of headache (aHR 0.33 for headache, 95% CI 0.13 - 0.87). Only 8 individuals (10.8% of all study subjects) were alive and receiving ART 2 years after the CM episode. CONCLUSIONS: Long-term outcomes of CM are poor in routine practice. Interventions to strengthen linkage to HIV treatment and care and continuation of secondary fluconazole prophylaxis are critical

Disengagement from care in a decentralised primary health care antiretroviral treatment programme: cohort study in rural South Africa.

OBJECTIVE: To determine rates of, and factors associated with, disengagement from care in a decentralised antiretroviral programme. METHODS: Adults (≥16 years) who initiated antiretroviral therapy (ART) in the Hlabisa HIV Treatment and Care Programme August 2004-March 2011 were included. Disengagement from care was defined as no clinic visit for 180 days, after adjustment for mortality. Cumulative incidence functions for disengagement from care, stratified by year of ART initiation, were obtained; competing-risks regression was used to explore factors associated with disengagement from care. RESULTS: A total of 4,674 individuals (median age 34 years, 29% male) contributed 13 610 person-years of follow-up. After adjustment for mortality, incidence of disengagement from care was 3.4 per 100 person-years (95% confidence interval (CI) 3.1-3.8). Estimated retention at 5 years was 61%. The risk of disengagement from care increased with each calendar year of ART initiation (P for trend 200 cells/μl respectively, compared with CD4 count <50 cells/μl). Of those disengaged from care with known outcomes, the majority (206/303, 68.0%) remained resident within the local community. CONCLUSIONS: Increasing disengagement from care threatens to limit the population impact of expanded antiretroviral coverage. The influence of both individual and programmatic factors suggests that alternative service delivery strategies will be required to achieve high rates of long-term retention

Decreased chronic morbidity but elevated HIV associated cytokine levels in HIV-infected older adults receiving HIV treatment: benefit of enhanced access to care?

BACKGROUND:The association of HIV with chronic morbidity and inflammatory markers (cytokines) in older adults (50+years) is potentially relevant for clinical care, but data from African populations is scarce. OBJECTIVE:To examine levels of chronic morbidity by HIV and ART status in older adults (50+years) and subsequent associations with selected pro-inflammatory cytokines and body mass index. METHODS:Ordinary, ordered and generalized ordered logistic regression techniques were employed to compare chronic morbidity (heart disease (angina), arthritis, stroke, hypertension, asthma and diabetes) and cytokines (Interleukins-1 and -6, C-Reactive Protein and Tumor Necrosis Factor-alpha) by HIV and ART status on a cross-sectional random sample of 422 older adults nested within a defined rural South African population based demographic surveillance. RESULTS:Using a composite measure of all morbidities, controlling for age, gender, BMI, smoking and wealth quintile, HIV-infected individuals on ART had 51% decreased odds (95% CI:0.26-0.92) of current morbidity compared to HIV-uninfected. In adjusted regression, compared to HIV-uninfected, the proportional odds (aPOR) of having elevated inflammation markers of IL6 (>1.56 pg/mL) was nearly doubled in HIV-infected individuals on (aPOR 1.84; 95%CI: 1.05-3.21) and not on (aPOR 1.94; 95%CI: 1.11-3.41) ART. Compared to HIV-uninfected, HIV-infected individuals on ART had >twice partial proportional odds (apPOR=2.30;p=0.004) of having non-clinically significant raised hsCRP levels(>1 ug/mL); ART-naïve HIV-infected individuals had >double apPOR of having hsCRP levels indicative of increased heart disease risk(>3.9 ug/mL;p=0.008). CONCLUSIONS:Although HIV status was associated with increased inflammatory markers, our results highlight reduced morbidity in those receiving ART and underscore the need of pro-actively extending these services to HIV-uninfected older adults, beyond mere provision at fixed clinics. Providing health services through regular community chronic disease screening would ensure health care reaches all older adults in need

Retention in HIV care for individuals not yet eligible for antiretroviral therapy: rural KwaZulu-Natal, South Africa.

OBJECTIVES: To determine retention in HIV care for individuals not yet eligible for antiretroviral therapy (ART) and to explore factors associated with retention in a rural public health HIV program. METHODS: HIV-infected adults (≥16 years) not yet eligible for ART, with CD4 cell count >200 cells per microliter from January 2007 to December 2007 were included in the analysis. Retention was defined by repeat CD4 count within 13 months. Factors associated with retention were assessed using logistic regression with clustering at clinic level. RESULTS: Four thousand two hundred twenty-three were included in the analysis (83.9% female). Overall retention was 44.9% with median time to return 201 days [interquartile range (IQR): 127-274]. Retention by initial CD4 count 201-350, 351-500, and >500 cells per microliter was 51.6% [95% confidence interval (CI): 49.1 to 54.0], 43.2% (95% CI: 40.5 to 45.9), and 34.9% (95% CI: 32.4 to 37.4), respectively. Compared with CD4 201-350 cells per microliter, higher initial CD4 count was significantly associated with lower odds of retention [CD4: 351-500 cells/μL adjusted odds ratio (aOR): 0.72, 95% CI: 0.62 to 0.84; CD4 >500 cells/μL aOR: 0.51, 95% CI: 0.44 to 0.60]. Male sex was independently associated with lower odds (aOR: 0.80, 95% CI: 0.67 to 0.96), and older age with higher odds of retention (for each additional year of age aOR: 1.03, 95% CI: 1.03 to 1.04). CONCLUSIONS: Retention in HIV care before eligibility for ART is poor, particularly for younger individuals and those at an earlier stage of infection. Further work to optimize and evaluate care and monitoring strategies is required to realize the full benefits of the rapid expansion of HIV programs in sub-Saharan Africa

Reduction in early mortality on antiretroviral therapy for adults in rural south africa since change in CD4+ cell count eligibility criteria

Objective: To explore the impact of expanded eligibility criteria for antiretroviral therapy (ART) on median CD4+ cell count at ART initiation and early mortality on ART. Methods: Analyses included all adults (16 years) initiated on first-line ART between August 2004 and July 2012. CD4+ cell count threshold 350 cells per microliter for all adults was implemented in August 2011. Early mortality was defined as any death within 91 days of ART initiation. Trends in baseline CD4+ cell count and early mortality were examined by year (August to July) of ART initiation. Competing risks analysis was used to examine early mortality. Results: A total of 19,080 adults (67.6% female) initiated ART. Median CD4+ cell count at ART initiation was 110-120 cells per microliter over the first 6 years, increasing marginally to 145 cells per microliter in 2010-2011 and more significantly to 199 cells per microliter in 2011-2012. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate was 19.4 per 100 personyears [95% confidence interval (CI) 18.2 to 20.7]. After adjustment for sex, age, baseline CD4+ cell count, and concurrent tuberculosis (TB), there was a 46% decrease in early mortality for those who initiated ART in 2011-2012 compared with the reference period 2008-2009 (subhazard ratio, 0.54; 95% CI: 0.41 to 0.71). Conclusions: Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rate in this primary health care programme. These findings provide strong support for national ART policies and highlight the importance of earlier ART initiation for achieving reductions in HIV-related mortality. Copyright © 2013 by Lippincott Williams & Wilkins

Scale-up of a decentralized HIV treatment programme in rural KwaZulu-Natal, South Africa: does rapid expansion affect patient outcomes?

OBJECTIVE: To describe the scale-up of a decentralized HIV treatment programme delivered through the primary health care system in rural KwaZulu-Natal, South Africa, and to assess trends in baseline characteristics and outcomes in the study population. METHODS: The programme started delivery of antiretroviral therapy (ART) in October 2004. Information on all patients initiated on ART was captured in the programme database and follow-up status was updated monthly. All adult patients (> 16 years) who initiated ART between October 2004 and September 2008 were included and stratified into 6-month groups. Clinical and sociodemographic characteristics were compared between the groups. Retention in care, mortality, loss to follow-up and virological outcomes were assessed at 12 months post-ART initiation. FINDINGS: A total of 5719 adults initiated on ART were included (67.9% female). Median baseline CD4+ lymphocyte count was 116 cells/μl (interquartile range, IQR: 53-173). There was an increase in the proportion of women who initiated ART while pregnant but no change in other baseline characteristics over time. Overall retention in care at 12 months was 84.0% (95% confidence interval, CI: 82.6-85.3); 10.9% died (95% CI: 9.8-12.0); 3.7% were lost to follow-up (95% CI: 3.0-4.4). Mortality was highest in the first 3 months after ART initiation: 30.1 deaths per 100 person-years (95% CI: 26.3-34.5). At 12 months 23.0% had a detectable viral load (> 25 copies/ml) (95% CI: 19.5-25.5). CONCLUSION: Outcomes were not affected by rapid expansion of this decentralized HIV treatment programme. The relatively high rates of detectable viral load highlight the need for further efforts to improve the quality of services