Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study

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-naïve 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/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.

Conclusions

HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors'' Summary.     

Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study

Background

Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART.

Methods

We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment.

Results

Between January 2001–January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm³) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71–4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95–5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08–4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7–52cells/mm³) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99–2.06) within the first 6-months of treatment.

Conclusions

HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS demonstrated a poorer immunologic response to ART than those without KS.     

Antiretroviral outcomes in South African prisoners: a retrospective cohort analysis

Background and Methods

Little is known about antiretroviral therapy (ART) outcomes in prisoners in Africa. We conducted a retrospective review of outcomes of a large cohort of prisoners referred to a public sector, urban HIV clinic. The review included baseline characteristics, sequential CD4 cell counts and viral load results, complications and co-morbidities, mortality and loss to follow-up up to 96 weeks on ART.

Findings

148 inmates (133 male) initiated on ART were included in the study. By week 96 on ART, 73% of all inmates enrolled in the study and 92% of those still accessing care had an undetectable viral load (<400copies/ml). The median CD4 cell count increased from 122 cells/mm³ at baseline to 356 cells/mm³ by 96 weeks. By study end, 96 (65%) inmates had ever received tuberculosis (TB) therapy with 63 (43%) receiving therapy during the study: 28% had a history of TB prior to ART initiation, 33% were on TB therapy at ART initiation and 22% developed TB whilst on ART. Nine (6%) inmates died, 7 in the second year on ART. Loss to follow-up (LTF) was common: 14 (9%) patients were LTF whilst still incarcerated, 11 (7%) were LTF post-release and 9 (6%) whose movements could not be traced. 16 (11%) inmates had inter-correctional facility transfers and 34 (23%) were released of whom only 23 (68%) returned to the ART clinic for ongoing follow-up.

Conclusions

Inmates responded well to ART, despite a high frequency of TB/HIV co-infection. Attention should be directed towards ensuring eligible prisoners access ART programs promptly and that inter-facility transfers and release procedures facilitate continuity of care. Institutional TB control measures should remain a priority.     

Point-of-Care CD4 Testing to Inform Selection of Antiretroviral Medications in South African Antenatal Clinics: A Cost-Effectiveness Analysis

Background

Many prevention of mother-to-child HIV transmission (PMTCT) programs currently prioritize antiretroviral therapy (ART) for women with advanced HIV. Point-of-care (POC) CD4 assays may expedite the selection of three-drug ART instead of zidovudine, but are costlier than traditional laboratory assays.

Methods

We used validated models of HIV infection to simulate pregnant, HIV-infected women (mean age 26 years, gestational age 26 weeks) in a general antenatal clinic in South Africa, and their infants. We examined two strategies for CD4 testing after HIV diagnosis: laboratory (test rate: 96%, result-return rate: 87%, cost: $14) and POC (test rate: 99%, result-return rate: 95%, cost: $26). We modeled South African PMTCT guidelines during the study period (WHO “Option A”): antenatal zidovudine (CD4 ≤350/μL) or ART (CD4>350/μL). Outcomes included MTCT risk at weaning (age 6 months), maternal and pediatric life expectancy (LE), maternal and pediatric lifetime healthcare costs (2013 USD), and cost-effectiveness ($/life-year saved).

Results

In the base case, laboratory led to projected MTCT risks of 5.7%, undiscounted pediatric LE of 53.2 years, and undiscounted PMTCT plus pediatric lifetime costs of $1,070/infant. POC led to lower modeled MTCT risk (5.3%), greater pediatric LE (53.4 years) and lower PMTCT plus pediatric lifetime costs ($1,040/infant). Maternal outcomes following laboratory were similar to POC (LE: 21.2 years; lifetime costs: $23,860/person). Compared to laboratory, POC improved clinical outcomes and reduced healthcare costs.

Conclusions

In antenatal clinics implementing Option A, the higher initial cost of a one-time POC CD4 assay will be offset by cost-savings from prevention of pediatric HIV infection.     

Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children

Background

In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6–36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth.

Methods

HIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions).

Results

In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures).

Conclusions

In this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.     

Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial

Objective

Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low–income African countries.

Methods

Setting: HIV clinics in Uganda and Zimbabwe. Design: Secondary exploratory cross-sectional analysis of the DART randomized controlled trial. Outcome Measures: Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ≥ 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without.

Results

A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ≥ 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV–1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis.

Conclusions

Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy.     

Obesity and Risk of Hip Fracture in Adults: A Meta-Analysis of Prospective Cohort Studies

Background

Many observational studies assessed the association between obesity and risk of hip fracture in adults, but reported controversial results. Our goal was to evaluate the association between obesity and risk of hip fracture in adults by conducting a meta-analysis of prospective cohort studies.

Methods

Three databases, PubMed, Embase and Web of Science, were searched through May 2012 to identify eligible cohort studies. Either a fixed- or a random-effects model was used to calculate the pooled relative risk (RR) with its 95% confidence interval (95%CI).

Results

Fifteen prospective cohort studies involving a total 3,126,313 participants were finally included into this meta-analysis. Overall, adults with obesity compared with the normal weight group had a significantly decreased risk of hip fracture (RR: 0.66, 95% CI 0.57 to 0.77, P<0.001). Meta-analyses by the adjusted status of RRs also suggested adults with obesity compared with the reference group had a significantly decreased risk of hip fracture (adjusted RR: 0.48, 95% CI 0.39 to 0.58, P<0.001; unadjusted RR: 0.66, 95% CI 0.56 to 0.78, P<0.001). Subgroup analyses by gender suggested individuals with obesity had a significantly decreased risk for developing hip fracture compared with the reference group in both men (RR 0.54, 95% CI 0.48 to 0.60, P<0.001) and women (RR 0.70, 95% CI 0.58 to 0.84, P<0.001). No evidence of publication bias was observed in this meta-analysis.

Conclusions

This meta-analysis of prospective cohort studies suggests that obesity significantly decreases the risk of hip fracture in adults, and obesity is probably a protective factor of hip fracture in adults.     

BMI and All‐cause Mortality Among Japanese Older Adults: Findings From the Japan Collaborative Cohort Study

The association between BMI and all‐cause mortality may vary with gender, age, and ethnic groups. However, few prospective cohort studies have reported the relationship in older Asian populations. We evaluated the association between BMI and all‐cause mortality in a cohort comprised 26,747 Japanese subjects aged 65–79 years at baseline (1988–1990). The study participants were followed for an average of 11.2 years. Proportional‐hazards regression models were used to estimate mortality hazard ratios (HRs) and 95% confidence intervals. Until 2003, 9,256 deaths occurred. The underweight group was associated with a statistically higher risk of all‐cause mortality compared with the mid‐normal‐range group (BMI: 20.0–22.9); resulting in a 1.78‐fold (95% confidence interval: 1.45–2.20) and 2.55‐fold (2.13–3.05) increase in mortality risk among severest thin men and women (BMI: <16.0), respectively. Even within the normal‐range group, the lower normal‐range group (BMI: 18.5–19.9) showed a statistically elevated risk. In contrast, being neither overweight (BMI: 25.0–29.9) nor obese (BMI: ≥30.0) elevated the risk among men; however among women, HR was slightly elevated in the obese group but not in the overweight group compared with the mid‐normal‐range group. Among Japanese older adults, a low BMI was associated with increased risk of all‐cause mortality, even among those with a lower normal BMI range. The wide range of BMI between 20.0 and 29.9 in both older men and women showed the lowest all‐cause mortality risk.     

Virologic,Immunologic and Clinical Responses in Foreign-Born versus US-Born HIV-1 Infected Adults Initiating Antiretroviral Therapy: An Observational Cohort Study

Introduction

Mortality rates within the first year of combination antiretroviral therapy (cART) initiation are several-fold higher in resource-limited countries than in resource-replete settings. However studies in western countries examining virologic, immunologic and clinical responses after cART initiation in indigenous versus non-indigenous populations have shown mixed results. This study aimed to determine whether there is a difference in these outcomes in a United States setting between foreign-born and US-born patients.

Methods

This retrospective observational cohort study of HIV-1 infected adults in one urban clinic in the United States compared virologic suppression, immune recovery and rates of AIDS defining events (ADEs) within the first year of cART using linear mixed effect models, log rank tests and Cox proportional hazard models. Data were analyzed for 94 foreign-born and 1242 US-born patients.

Results

Foreign-born patients were younger (31.7 years versus 38.5 years), more often female (38.3% versus 27.1%), less often injection drug users (3.2% versus 9.5%) or men who have sex with men (19.0% versus 54.5%), and had higher loss to follow-up rates (14.9% versus 6.2%). No significant differences were detected between the groups in suppression of plasma HIV-1 RNA, CD4+ cell recovery or development of ADEs.

Conclusions

During the first year on cART, virologic suppression, immune recovery and development of ADEs were comparable between foreign-born and US-born patients in care in a US clinic. Differential rates of loss to follow-up warrant further investigation in the foreign-born population.     

Quality of Life Outcomes of Antiretroviral Treatment for HIV/AIDS Patients in Vietnam

Objective

This study assessed health-related quality of life (HRQOL) and its related factors in HIV/AIDS patients taking antiretroviral treatment (ART) in Vietnam.

Methods

A cross-sectional study was conducted with 1016 patients (36.2% women, mean age = 35.4) in three epicenters of Vietnam, including Hanoi, Hai Phong, and Ho Chi Minh City. HRQOL was assessed using the Vietnamese version of the WHOQOL-HIV BREF. Factor analysis classified measure items into six HRQOL dimensions, namely Physical, Morbidity, Social, Spirituality, Performance, and Environment. Tobit censored regression models were applied to determine associations of patient’s characteristics and HRQOL domain scores.

Results

Internal consistency reliability of the six domains ranged from 0.69 to 0.89. The WHOQOL-HIV BREF had a good discriminative validity with patient’s disease stages, CD4 cell counts, and duration of ART. In a band score of (4, 20), six domains were moderate; “Environment” had the highest score (13.8±2.8), and “Social” had the lowest score (11.2±3.3). Worse HRQOL were observed in patients at provincial and district clinics. Those patients who were male, had higher educational attainment, and are employed, reported better HRQOL. In reduced regression models, poorer HRQOL was found in patients who had advanced HIV infection and had CD4 cell count <200 cells/mL. Patients reported significantly poorer Physical and Social in the 1^st year ART, but moderately better Performance, Morbidity, Spirituality, and Environment from the 2^nd year ART, compared to those not-yet-on ART.

Conclusion

Strengthening the quality of ART services at the provincial and district levels, gender-specific impact mitigation, and early treatment supports are recommended for further expansion of ART services in Vietnam. Regular assessments of HRQOL may provide important indicators for monitoring and evaluating HIV/AIDS services.     

Retention in Care and Outpatient Costs for Children Receiving Antiretroviral Therapy in Zambia: A Retrospective Cohort Analysis

Background

There are few published estimates of the cost of pediatric antiretroviral therapy (ART) in Africa. Our objective was to estimate the outpatient cost of providing ART to children remaining in care at six public sector clinics in Zambia during the first three years after ART initiation, stratified by service delivery site and time on treatment.

Methods

Data on resource utilization (drugs, diagnostics, outpatient visits, fixed costs) and treatment outcomes (in care, died, lost to follow up) were extracted from medical records for 1,334 children at six sites who initiated ART at <15 years of age between 2006 and 2011. Fixed and variable unit costs (reported in 2011 USD) were estimated from the provider’s perspective using site level data.

Results

Median age at ART initiation was 4.0 years; median CD4 percentage was 14%. One year after ART initiation, 73% of patients remained in care, ranging from 60% to 91% depending on site. The average annual outpatient cost per patient remaining in care was $209 (95% CI, $199–$219), ranging from $116 (95% CI, $107–$126) to $516 (95% CI, $499–$533) depending on site. Average annual costs decreased as time on treatment increased. Antiretroviral drugs were the largest component of all outpatient costs (>50%) at four sites. At the two remaining sites, outpatient visits and fixed costs together accounted for >50% of outpatient costs. The distribution of costs is slightly skewed, with median costs 3% to 13% lower than average costs during the first year after ART initiation depending on site.

Conclusions

Outpatient costs for children initiating ART in Zambia are low and comparable to reported outpatient costs for adults. Outpatient costs and retention in care vary widely by site, suggesting opportunities for efficiency gains. Taking advantage of such opportunities will help ensure that targets for pediatric treatment coverage can be met.     

Increasing Transfers-Out from an Antiretroviral Treatment Service in South Africa: Patient Characteristics and Rates of Virological Non-Suppression

Objectives

To determine the proportion, characteristics and outcomes of patients who transfer-out from an antiretroviral therapy (ART) service in a South African township.

Methods

This retrospective cohort study included all patients aged ≥15 years who enrolled between September 2002 and December 2009. Follow-up data were censored in December 2010. Kaplan-Meier survival analysis was used to describe time to transfer-out and cox proportional hazard analysis was used to determine associated risk factors.

Results

4511 patients (4003 ART-naïve and 508 non-naïve at baseline) received ART during the study period. Overall, 597 (13.2%) transferred out. The probability of transferring out by one year of ART steadily increased from 1.4% in 2002/2004 cohort to 8.9% for the 2009 cohort. Independent risk factors for transfer-out were more recent calendar year of enrolment, younger age (≤25 years) and being ART non-naïve at baseline (i.e., having previously transferred into this clinic from another facility). The proportions of patients transferred out who had a CD4 cell count <200 cells/µL and/or a viral load ≥1000 copies/mL were 19% and 20%, respectively.

Conclusions

With scale-up of ART over time, an increasing proportion of patients are transferring between ART services and information systems are needed to track patients. Approximately one-fifth of these have viral loads >1000 copies/mL around the time of transfer, suggesting the need for careful adherence counseling and assessment of medication supplies among those planning transfer.     

Better Antiretroviral Therapy Outcomes at Primary Healthcare Facilities: An Evaluation of Three Tiers of ART Services in Four South African Provinces

Background

There are conflicting reports of antiretroviral therapy (ART) effectiveness comparisons between primary healthcare (PHC) facilities and hospitals in low-income settings. This comparison has not been evaluated on a broad scale in South Africa.

Methodology/Principal Findings

A retrospective cohort study was conducted including ART-naïve adults from 59 facilities in four provinces in South Africa, enrolled between 2004 and 2007. Kaplan-Meier estimates, competing-risks Cox regression, generalised estimating equation population-averaged models and logistic regression were used to compare death, loss to follow-up (LTFU) and virological suppression (VS) between PHC, district and regional hospitals. 29 203 adults from 47 PHC facilities, nine district hospitals and three regional hospitals were included. Patients at PHC facilities had more advanced WHO stage disease when starting ART. Retention in care was 80.1% (95% CI: 79.3%–80.8%), 71.5% (95% CI: 69.1%–73.8%) and 68.7% (95% CI: 67.0%–69.7%) at PHC, district and regional hospitals respectively, after 24 months of treatment (P<0.0001). In adjusted regression analyses, LTFU was independently increased at regional hospitals (aHR 2.19; 95% CI: 1.94−2.47) and mortality was independently elevated at district hospitals (aHR 1.60; 95% CI: 1.30−1.99) compared to PHC facilities after 12 months of ART. District and regional hospital patients had independently reduced probabilities of VS, aOR 0.76 (95% CI: 0.59−0.97) and 0.64 (95% CI: 0.56−0.75) respectively compared to PHC facilities over 24 months of treatment.

Conclusions/Significance

ART outcomes were superior at PHC facilities, despite PHC patients having more advanced clinical stage disease when starting ART, suggesting that ART can be adequately provided at this level and supporting the South African government''s call for rapid up-scaling of ART at the primary level of care. Further prospective research is required to determine the degree to which outcome differences are attributable to either facility level characteristics or patient co-morbidity at hospital level.     

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9–8.4 and pooled HR = 8.7, 95% CI 6.6–11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4–2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1–1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1–2.4 and HR = 2.4, 95% CI 1.5–3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0–1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0–2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.     

A South African Public-Private Partnership HIV Treatment Model: Viability and Success Factors

Introduction

The increasing number of people requiring HIV treatment in South Africa calls for efficient use of its human resources for health in order to ensure optimum treatment coverage and outcomes. This paper describes an innovative public-private partnership model which uses private sector doctors to treat public sector patients and ascertains the model’s ability to maintain treatment outcomes over time.

Methods

The study used a retrospective design based on the electronic records of patients who were down-referred from government hospitals to selected private general medical practitioners (GPs) between November 2005 and October 2012. In total, 2535 unique patient records from 40 GPs were reviewed. The survival functions for mortality and attrition were calculated. Cumulative incidence of mortality for different time cohorts (defined by year of treatment initiation) was also established.

Results

The median number of patients per GP was 143 (IQR: 66–246). At the time of down-referral to private GPs, 13.8% of the patients had CD4 count <200 cell/mm³, this proportion reduced to 6.6% at 12 months and 4.1% at 48 months. Similarly, 88.4% of the patients had suppressed viral load (defined as HIV-1 RNA <400 copies/ml) at 48 months. The patients’ probability of survival at 12 and 48 months was 99.0% (95% CI: 98.4%–99.3%) and 89.0% (95% CI: 87.1%–90.0%) respectively. Patient retention at 48 months remained high at 94.3% (95% CI: 93.0%–95.7%).

Conclusions

The study findings demonstrate the ability of the GPs to effectively maintain patient treatment outcomes and potentially contribute to HIV treatment scale-up with the relevant support mechanism. The model demonstrates how an assisted private sector based programme can be effectively and efficiently used to either target specific health concerns, key populations or serve as a stop-gap measure to meet urgent health needs.     

Life Course Trajectories of Labour Market Participation among Young Adults Who Experienced Severe Alcohol-Related Health Outcomes: A Retrospective Cohort Study

BackgroundLong-term employment trajectories of young problem drinkers are poorly understood.MethodsWe constructed retrospective labour market participation histories at ages 18–34 of 64 342 persons born in 1969–1982. Beginning from the year of each subject’s 18^th birthday, we extracted information from the records of Statistics Finland on educational attainment, main type of economic activity, months in employment, and months in unemployment for a minimum of seven years (range 7–16 years). We used information on the timing of alcohol-related hospitalizations and deaths in the same period to define problem drinkers with early onset limited course, early onset persistent course, and late onset problem drinking.ResultsEarly onset limited course problem drinkers improved their employment considerably by age, whereas early onset persistent problem drinkers experienced a constant decline in their employment by age. From the age of 18 to 34, early onset persistent problem drinkers were in employment merely 12% of the time, in comparison with 39% among the early onset limited course problem drinkers, and 58% among the general population.ConclusionsThese results indicate that young adults who were retrospectively defined as having early onset persistent course problem drinking were extensively marginalized from the labour market early on during their life course, and that their employment trajectory was significantly worse compared to other problem drinkers.     

The Association between Hypertension and Depression and Anxiety Disorders: Results from a Nationally-Representative Sample of South African Adults

Objective

Growing evidence suggests high levels of comorbidity between hypertension and mental illness but there are few data from low- and middle-income countries. We examined the association between hypertension and depression and anxiety in South Africa.

Methods

Data come from a nationally-representative survey of adults (n = 4351). The Composite International Diagnostic Interview was used to measure DSM-IV mental disorders during the previous 12-months. The relationships between self-reported hypertension and anxiety disorders, depressive disorders and comorbid anxiety-depression were assessed after adjustment for participant characteristics including experience of trauma and other chronic physical conditions.

Results

Overall 16.7% reported a previous medical diagnosis of hypertension, and 8.1% and 4.9% were found to have a 12-month anxiety or depressive disorder, respectively. In adjusted analyses, hypertension diagnosis was associated with 12-month anxiety disorders [Odds ratio (OR) = 1.55, 95% Confidence interval (CI) = 1.10–2.18] but not 12-month depressive disorders or 12-month comorbid anxiety-depression. Hypertension in the absence of other chronic physical conditions was not associated with any of the 12-month mental health outcomes (p-values all <0.05), while being diagnosed with both hypertension and another chronic physical condition were associated with 12-month anxiety disorders (OR = 2.25, 95% CI = 1.46–3.45), but not 12-month depressive disorders or comorbid anxiety-depression.

Conclusions

These are the first population-based estimates to demonstrate an association between hypertension and mental disorders in sub-Saharan Africa. Further investigation is needed into role of traumatic life events in the aetiology of hypertension as well as the temporality of the association between hypertension and mental disorders.