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1.  The association between timing of initiation of antenatal care and stillbirths: a retrospective cohort study of pregnant women in Cape Town, South Africa 
There is renewed interest in stillbirth prevention for lower-middle income countries. Early initiation of and properly timed antenatal care (ANC) is thought to reduce the risk of many adverse birth outcomes. To this end we examined if timing of the first ANC visit influences the risk of stillbirth.
We conducted an analysis of a retrospective cohort of women (n = 34,671) with singleton births in a public perinatal service in Cape Town, South Africa. The main exposure was the gestational age at the first ANC visit. Bivariable analyses examining maternal characteristics by stillbirth status and gestational age at the first ANC visit, were conducted. Logistic regression, adjusting for maternal characteristics, was conducted to determine the risk of stillbirth.
Of the 34,671 women who initiated ANC, 27,713 women (80%) were retained until delivery. The population stillbirth rate was 4.3 per 1000 births. The adjusted models indicated there was no effect of gestational age at first ANC visit on stillbirth outcomes when analyzed as a continuous variable (aOR 1.01; 95% CI: 0.99-1.04) or in trimesters (2nd Trimester aOR 0.78, 95% CI: 0.39-1.59; 3rd Trimester OR 1.03, 95% CI: 0.50-2.13, both with 1st Trimester as reference category). The findings were unchanged in sensitivity analyses of unobserved outcomes in non-retained women.
The timing of a woman’s first ANC visit may not be an important determinant of stillbirths in isolation. Further research is required to examine how quality of care, incorporating established, effective biomedical interventions, influences outcomes in this setting.
PMCID: PMC4062506  PMID: 24923284
Stillbirths; Antenatal care; Gestational age; Prenatal care; South Africa
2.  Mother-to-child transmission of HIV in a community-based antiretroviral clinic in South Africa 
To examine the uptake of ART among pregnant women referred to an ART service and the associated rates and risk factors for vertical HIV transmission.
Retrospective analysis of an observational cohort at a community ART clinic in Cape Town.
Between 2002 and 2008, 367 treatment-naïve pregnant women accessed the clinic. The median age was 27.5 years, and median gestation at presentation was 28 weeks. The median baseline CD4 count and viral load were 134 cells/µl and 28 282 copies/ml. Two hundred and sixty-five women (72%) commenced ART before giving birth, 73 women (20%) were referred for prevention of mother-to-child transmission therapy (PMTCT), and 29 (8%) received no intervention. Among ART-eligible women, 13% were lost to follow-up. Of those starting ART, median duration of therapy prior to birth was 7.6 weeks (interquartile range (IQR) 4 – 11.9). The HIV transmission rate was 5.1% (95% confidence interval (CI) 2.8 – 9.0%). Factors associated with transmission were advanced maternal WHO disease stage (odds ratio (OR) 9.57, p=0.02), and follow-up viral load above 50 copies/ml (OR 3.64, p=0.03). Each additional week on ART reduced transmission by 20% (p=0.05). There was no HIV transmission among women who received more than 8 weeks’ therapy.
The rate of HIV transmission in this study was higher than reported in high-income countries. Prevention of vertical transmission with ART was hindered by women presenting late in pregnancy and with advanced stage of HIV disease. Interventions that facilitate earlier ART commencement and improve programmatic retention of pregnant women are required.
PMCID: PMC3954611  PMID: 21414276
3.  Rates of tuberculosis transmission to children and adolescents in a community with high adult HIV prevalence 
PMCID: PMC3816246  PMID: 18558885
tuberculin skin test; HIV; TB transmission; children; annual risk of TB infection
4.  Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa 
AIDS (London, England)  2008;22(15):10.1097/QAD.0b013e32830007cd.
Two-thirds of the world's HIV-infected people live in sub-Saharan Africa and more than 1.5 million of them die annually. As access to antiretroviral treatment (ART) has expanded within the region, early pessimism concerning the delivery of ART using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, however, early mortality rates in sub-Saharan Africa are very high; between 8% and 26% of patients die in the first year of ART, with most deaths occurring in the first few months. Patients typically access ART with advanced symptomatic disease, and mortality is strongly associated with baseline CD4 cell count <50 cells/μL and WHO stage 4 disease (AIDS). Although data are limited, leading causes of death appear to be tuberculosis, acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome. Mortality rates are likely to depend not only on the care delivered by ART programmes, but more fundamentally on how advanced disease is at programme enrolment and the quality of preceding health-care. In addition to improving delivery of ART and providing this free of charge to the patient, strategies to reduce mortality must include earlier diagnosis of HIV infection, strengthening of longitudinal HIV care and timely initiation of ART. Health systems delays in ART initiation must be minimised, especially in patients who present with advanced immunodeficiency.
PMCID: PMC3816249  PMID: 18784453
HIV; AIDS; antiretroviral treatment; HAART; ART; mortality; death; Africa
5.  Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa 
AIDS (London, England)  2009;23(13):1717-1725.
To determine the short-term and long-term risks of tuberculosis (TB) associated with CD4 cell recovery during antiretroviral therapy (ART).
Observational community-based ART cohort in South Africa.
TB incidence was determined among patients (n = 1480) receiving ART for up to 4.5 years in a South African community-based service. Updated CD4 cell counts were measured 4-monthly. Person-time accrued within a range of CD4 cell count strata (CD4 cell strata) was calculated and used to derive CD4 cell-stratified TB rates. Factors associated with incident TB were identified using Poisson regression models.
Two hundred and three cases of TB were diagnosed during 2785 person-years of observation (overall incidence, 7.3 cases/100 person-years). During person-time accrued within CD4 cell strata 0–100, 101–200, 201–300, 301–400, 401–500 and more than 500 cells/µl unadjusted TB incidence rates were 16.8, 9.3, 5.5, 4.6, 4.2 and 1.5 cases/100 person-years, respectively (P < 0.001). During early ART (first 4 months), adjusted TB rates among those with CD4 cell counts 0–200 cells/µl were 1.7-fold higher than during long-term ART (P = 0.026). Updated CD4 cell counts were the only patient characteristic independently associated with long-term TB risk.
Updated CD4 cell counts were the dominant predictor of TB risk during ART in this low-resource setting. Among those with baseline CD4 cell counts less than 200 cells/µl, the excess adjusted risk of TB during early ART was consistent with ‘unmasking’ of disease missed at baseline screening. TB incidence rates at CD4 cell counts of 200–500 cells/µl remained high and adjunctive interventions are required. TB prevention would be improved by ART policies that minimized the time patients spend with CD4 cell counts below a threshold of 500 cells/µl.
PMCID: PMC3801095  PMID: 19461502
Africa; antiretroviral; CD4 cell; HIV; immune reconstitution; resource-limited country; tuberculosis
6.  Antiretroviral therapy and TB notification rates in a high HIV prevalence South African community 
Antiretroviral therapy (ART) has been proposed as an intervention for reducing tuberculosis (TB) burdens in areas with high HIV prevalence. However, little data is available on the impact of ART on population-level TB.
Trends in adult TB case fatality and notifications were assessed prior to and during increasing ART coverage in a well-defined peri-urban community, from 1997 to 2008. Mean changes in TB rates were measured using linear autoregression models. ART coverage increased from 1% in 2003, to 5%, 13% and 21% of HIV-infected population in 2004, 2005 and 2008 respectively.
From 1997 to end of 2004 TB notification rates increased by an average of 187 cases/100,000/yr (p<0.001), reaching a peak of 2,536/100,000 in 2005. From 2005 to 2008, TB notification rates declined by approximately 183 cases/100,000/yr (p<0.001). TB rates were initially stable in HIV-uninfected individuals, but declined moderately from 2005. TB rates declined in HIV-infected adults from 6,513/100,000 in 2005 to 4,741/100,000 in 2008. The predominant decline in TB notifications occurred among HIV-infected patients receiving ART (1,156 cases/100,000/yr) and was less marked in those not receiving ART (416cases/100,000/yr). Similarly, TB case fatality was constant for HIV-uninfected individuals but declined in HIV-infected individuals from 23% in 2002 to 8% in 2008 (p=0.01).
In this community heavily affected by both HIV and TB epidemics, rapid and high ART coverage was associated with significant reductions in TB notifications and TB-associated case fatality.
PMCID: PMC3801097  PMID: 21317585
tuberculosis; notification rates; HIV; antiretroviral; community
7.  Comparison of point-of-care versus laboratory-based CD4 cell enumeration in HIV-positive pregnant women 
Early initiation of antiretroviral therapy (ART) in eligible pregnant women is a key intervention for prevention of mother-to-child transmission (PMTCT) of HIV. However, in many settings in sub-Saharan Africa where ART-eligibility is determined by CD4 cell counts, limited access to laboratories presents a significant barrier to rapid ART initiation. Point-of-care (POC) CD4 cell count testing has been suggested as one approach to overcome this challenge, but there are few data on the agreement between POC CD4 cell enumeration and standard laboratory-based testing.
Working in a large antenatal clinic in Cape Town, South Africa, we compared POC CD4 cell enumeration (using the Alere PimaTM Analyzer) to laboratory-based flow cytometry in consecutive HIV-positive pregnant women. Bland–Altman methods were used to compare the two methods, including analyses by subgroups of participant gestational age.
Among the 521 women participating, the median gestational age was 23 weeks, and the median CD4 cell count according to POC and laboratory-based methods was 388 and 402 cells/µL, respectively. On average, the Pima POC test underestimated CD4 cell count relative to flow cytometry: the mean difference (laboratory test minus Pima POC) was 22.7 cells/µL (95% CI, 16.1 to 29.2), and the limits of agreement were −129.2 to 174.6 cells/µL. When analysed by gestational age categories, there was a trend towards increasing differences between laboratory and POC testing with increasing gestational age; in women more than 36 weeks’ gestation, the mean difference was 45.0 cells/µL (p=0.04).
These data suggest reasonable overall agreement between Pima POC CD4 testing and laboratory-based flow cytometry among HIV-positive pregnant women. The finding for decreasing agreement with increasing gestational age requires further investigation, as does the operational role of POC CD4 testing to increase access to ART within PMTCT programmes.
PMCID: PMC3776301  PMID: 24044627
point-of-care test; CD4 cell count; reliability; pregnancy; HIV; antiretroviral therapy; South Africa
8.  Viewpoint Men and antiretroviral therapy in Africa: our blindspot 
PMCID: PMC3749374  PMID: 21418449
9.  Screening for Serious Mental Illness in the General Population with the K6 screening scale: Results from the WHO World Mental Health (WMH) Survey Initiative 
Data are reported on the background and performance of the K6 screening scale for serious mental illness (SMI) in the World Health Organization (WHO) World Mental Health (WMH) surveys. The K6 is a 6-item scale developed to provide a brief valid screen for DSM-IV SMI based on the criteria in the US ADAMHA Reorganization Act. Although methodological studies have documented good K6 validity in a number of countries, optimal scoring rules have never been proposed. Such rules are presented here based on analysis of K6 data in nationally or regionally representative WMH surveys in 14 countries (combined n = 41,770 respondents). Twelve-month prevalence of DSM-IV SMI was assessed with the fully-structured WHO Composite International Diagnostic Interview. Nested logistic regression analysis was used to generate estimates of the predicted probability of SMI for each respondent from K6 scores taking into consideration the possibility of variable concordance as a function of respondent age, gender, education, and country. Concordance, assessed by calculating the area under the receiver operating characteristic curve (AUC), was generally substantial (Median .83; Range .76-.89; Inter-quartile range .81-.85). Based on this result, optimal scaling rules are presented for use by investigators working with the K6 scale in the countries studied.
PMCID: PMC3659799  PMID: 20527002
K6 screening scale; psychiatric epidemiology; serious mental illness (SMI)
10.  Integration of Antiretroviral Therapy Services into Antenatal Care Increases Treatment Initiation during Pregnancy: A Cohort Study 
PLoS ONE  2013;8(5):e63328.
Initiation of antiretroviral therapy (ART) during pregnancy is critical to promote maternal health and prevent mother-to-child HIV transmission (PMTCT). The separation of services for antenatal care (ANC) and ART may hinder antenatal ART initiation. We evaluated ART initiation during pregnancy under different service delivery models in Cape Town, South Africa.
A retrospective cohort study was conducted using routinely collected clinic data. Three models for ART initiation in pregnancy were evaluated ART ‘integrated’ into ANC, ART located ‘proximal’ to ANC, and ART located some distance away from ANC (‘distal’). Kaplan-Meier methods and Poisson regression were used to examine the association between service delivery model and antenatal ART initiation.
Among 14 617 women seeking antenatal care in the three services, 30% were HIV-infected and 17% were eligible for ART based on CD4 cell count <200 cells/µL. A higher proportion of women started ART antenatally in the integrated model compared to the proximal or distal models (55% vs 38% vs 45%, respectively, global p = 0.003). After adjusting for age and gestation at first ANC visit, women who at the integrated service were significantly more likely to initiate ART antenatally (rate ratio 1.33; 95% confidence interval: 1.09–1.64) compared to women attending the distal model; there was no difference between the proximal and distal models in antenatal ART initiation however (p = 0.704).
Integration of ART initiation into ANC is associated with higher levels of ART initiation in pregnancy. This and other forms of service integration may represent a valuable intervention to enhance PMTCT and maternal health.
PMCID: PMC3656005  PMID: 23696814
11.  Early clinical signs in neonates with hypoxic ischemic encephalopathy predict an abnormal amplitude-integrated electroencephalogram at age 6 hours 
BMC Pediatrics  2013;13:52.
An early clinical score predicting an abnormal amplitude-integrated electroencephalogram (aEEG) or moderate-severe hypoxic ischemic encephalopathy (HIE) may allow rapid triage of infants for therapeutic hypothermia. We aimed to determine if early clinical examination could predict either an abnormal aEEG at age 6 hours or moderate-severe HIE presenting within 72 hours of birth.
Sixty infants ≥ 36 weeks gestational age were prospectively enrolled following suspected intrapartum hypoxia and signs of encephalopathy. Infants who were moribund, had congenital conditions that could contribute to the encephalopathy or had severe cardio-respiratory instability were excluded. Predictive values of the Thompson HIE score, modified Sarnat encephalopathy grade (MSEG) and specific individual signs at age 3–5 hours were calculated.
All of the 60 infants recruited had at least one abnormal primitive reflex. Visible seizures and hypotonia at 3–5 hours were strongly associated with an abnormal 6-hour aEEG (specificity 88% and 92%, respectively), but both had a low sensitivity (47% and 33%, respectively). Overall, 52% of the infants without hypotonia at 3–5 hours had an abnormal 6-hour aEEG. Twelve of the 29 infants (41%) without decreased level of consciousness at 3–5 hours had an abnormal 6-hour aEEG (sensitivity 67%; specificity 71%). A Thompson score ≥ 7 and moderate-severe MSEG at 3–5 hours, both predicted an abnormal 6-hour aEEG (sensitivity 100 vs. 97% and specificity 67 vs. 71% respectively). Both assessments predicted moderate-severe encephalopathy within 72 hours after birth (sensitivity 90%, vs. 88%, specificity 92% vs. 100%). The 6-hour aEEG predicted moderate-severe encephalopathy within 72 hours (sensitivity 75%, specificity 100%) but with lower sensitivity (p = 0.0156) than the Thompson score (sensitivity 90%, specificity 92%). However, all infants with a normal 3- and 6-hour aEEG with moderate-severe encephalopathy within 72 hours who were not cooled had a normal 24-hour aEEG.
The encephalopathy assessment described by the Thompson score at age 3–5 hours is a sensitive predictor of either an abnormal 6-hour aEEG or moderate-severe encephalopathy presenting within 72 hours after birth. An early Thompson score may be useful to assist with triage and selection of infants for therapeutic hypothermia.
PMCID: PMC3635928  PMID: 23574923
Asphyxia; Neonate; Hypoxic ischemic encephalopathy; Electroencephalogram; aEEG; Prognostic
12.  Increasing Transfers-Out from an Antiretroviral Treatment Service in South Africa: Patient Characteristics and Rates of Virological Non-Suppression 
PLoS ONE  2013;8(3):e57907.
To determine the proportion, characteristics and outcomes of patients who transfer-out from an antiretroviral therapy (ART) service in a South African township.
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.
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.
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.
PMCID: PMC3589459  PMID: 23472118
13.  Complications of Antiretroviral Therapy Initiation in Hospitalised Patients with HIV-Associated Tuberculosis 
PLoS ONE  2013;8(2):e54145.
HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries.
Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded.
Between May 2009 and November 2010, 112 patients (60% female), with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm3 (IQR 31–106) and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68%) developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%.
High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1st three months following ART initiation.
PMCID: PMC3568128  PMID: 23408935
14.  Linkage of HIV-Infected Infants from Diagnosis to Antiretroviral Therapy Services across the Western Cape, South Africa 
PLoS ONE  2013;8(2):e55308.
Early infant diagnosis (EID) of HIV infection is an important service to reduce paediatric morbidity and mortality related to HIV/AIDS. Although South Africa has a national EID programme based on PCR testing, there are no population-wide data on the linkage of infants testing HIV PCR-positive to HIV care and treatment services.
We conducted a retrospective analysis of all public sector laboratory data from across the Western Cape province between 2005 and 2011. We linked positive HIV PCR results to subsequent HIV viral load testing to determine the proportion of infants who were successfully linked to HIV care.
A total of 83 698 unique infant HIV PCR tests were documented, of which 6322 (8%) were PCR positive. The proportion of PCR-positive children declined from 12% in 2005 to 3% in 2011. Of the children testing PCR-positive, 4105 (65%) had subsequent viral load testing indicating successful linkage to care. The proportion of successfully linked infants increased from 54% in 2005 to 71% in 2010, while the median delay in days to successful linkage decreased from 146 days in 2005 to 33 days in 2010.
From 2005 to 2011 there has been a reduction in the proportion of children testing HIV PCR-positive, and an increase in the proportion of infected infants successfully linked to HIV care and treatment, in this setting. However a large proportion of infected infants remain unlinked to antiretroviral therapy services and there is a clear need for interventions to further strengthen EID programmes.
PMCID: PMC3566187  PMID: 23405133
15.  Immune Activation in the Female Genital Tract During HIV Infection Predicts Mucosal CD4 Depletion and HIV Shedding 
The Journal of Infectious Diseases  2011;204(10):1550-1556.
Plasma viral load predicts genital tract human immunodeficiency virus (HIV) shedding in HIV-infected women. We investigated whether local mucosal T-cell activation (HLA-DR, CD38, CCR5, and Ki67) contributed to HIV shedding in the genital tracts of HIV-infected women. We showed that cervical cytobrush-derived T cells expressed higher frequencies of T-cell activation markers (CD38+ and HLA-DR+) than blood-derived T cells. Expression was significantly higher in HIV-infected women than in uninfected women. We found that the frequency of activated proliferating cervical T cells (Ki67+; Ki67+CCR5+) broadly predicted HIV shedding in the genital tract in HIV-infected women, independently of plasma viral loads. Furthermore, activated cervical T cells (HLA-DR+CD38+ and HLA-DR+CCR5+) and local HIV shedding were independently associated with CD4 depletion in the genital tract. These data suggest that the presence of high frequencies of activated T cells in the female genital mucosa during HIV infection facilitates both local HIV shedding and CD4 T-cell depletion.
PMCID: PMC3192190  PMID: 21940422
16.  Effect of Caregivers' Depression and Alcohol Use on Child Antiretroviral Adherence in South Africa 
AIDS Patient Care and STDs  2011;25(10):595-600.
Pediatric antiretroviral adherence is difficult to assess, and subjective measures are affected by reporting bias, which in turn may depend on psychosocial factors such as alcohol use and depression. We enrolled 56 child–caregiver dyads from Cape Town, South Africa and followed their adherence over 1 month via various methods. The Alcohol Use Disorder Inventory Tool and Beck Depression Inventory 1 were used to assess these factors and their affect on pediatric adherence. The median age of the children was 4 years, and median time on antiretrovirals was 20 months. Increased time on ART was associated with poorer adherence via 3-day recall (3DR; p=0.03). Ethanol use was inversely associated with adherence by both subjective measures, 3DR and visual analogue scale (VAS) (both p<0.01), and with Medication Event Monitoring System (MEMS) adherence as a continuous variable. In a multivariate analysis predicting MEMS adherence greater than 95%, including variables that were associated with adherence in univariate analyses, having a mother as a caregiver and shorter time on highly active antiretroviral therapy (HAART) were significantly associated with adherence (odds ratio [OR] 19.2; 95% confidence interval [CI] 1.1–327 and 0.9; 95% CI 0.9–0.99). Pediatric adherence is affected by caregiver alcohol use, but caregiver relationship to the child is most important. This small study suggests that interventions should aim to keep mothers healthy and alive, as well as alcohol-free.
PMCID: PMC3183652  PMID: 21470047
17.  Mental illness and lost income among adult South Africans 
Little is known regarding the links between mental disorder and lost income in low- and middle-income countries. The purpose of this study was to investigate the association between mental disorder and lost income in the first nationally representative psychiatric epidemiology survey in South Africa.
A probability sample of South African adults was administered the World Health Organization Composite International Diagnostic Interview schedule to assess the presence of mental disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, version IV.
The presence of severe depression or anxiety disorders was associated with a significant reduction in earnings in the previous 12 months among both employed and unemployed South African adults (p = 0.0043). In simulations of costs to individuals, the mean estimated lost income associated with severe depression and anxiety disorders was $4,798 per adult per year, after adjustment for age, gender, substance abuse, education, marital status, and household size. Projections of total annual cost to South Africans living with these disorders in lost earnings, extrapolated from the sample, were $3.6 billion. These data indicate either that mental illness has a major economic impact, through the effect of disability and stigma on earnings, or that people in lower income groups are at increased risk of mental illness. The indirect costs of severe depression and anxiety disorders stand in stark contrast with the direct costs of treatment in South Africa, as illustrated by annual government spending on mental health services, amounting to an estimated $59 million for adults.
The findings of this study support the economic argument for investing in mental health care as a means of mitigating indirect costs of mental illness.
PMCID: PMC3627034  PMID: 23007296
Income; Mental disorder; South Africa; Economics; Health policy
18.  Systemic delays in the initiation of antiretroviral therapy during pregnancy do not improve outcomes of HIV-positive mothers: a cohort study 
Antiretroviral therapy (ART) initiation in eligible HIV-infected pregnant women is an important intervention to promote maternal and child health. Increasing the duration of ART received before delivery plays a major role in preventing vertical HIV transmission, but pregnant women across Africa experience significant delays in starting ART, partly due the perceived need to deliver ART counseling and patient education before ART initiation. We examined whether delaying ART to provide pre-ART counseling was associated with improved outcomes among HIV-infected women in Cape Town, South Africa.
We undertook a retrospective cohort study of 490 HIV-infected pregnant women referred to initiate treatment at an urban ART clinic. At this clinic all patients including pregnant women are screened by a clinician and then undergo three sessions of counseling and patient education prior to starting treatment, commonly introducing delays of 2–4 weeks before ART initiation. Data on viral suppression and retention in care after ART initiation were taken from routine clinic records.
A total of 382 women initiated ART before delivery (78%); ART initiation before delivery was associated with earlier gestational age at presentation to the ART service (p < 0.001). The median delay between screening and ART initiation was 21 days (IQR, 14–29 days). Overall, 84.7%, 79.6% and 75.0% of women who were pregnant at the time of ART initiation were retained in care at 4, 8 and 12 months after ART initiation, respectively. Among those retained, 91% were virally suppressed at each follow-up visit. However the delay from screening to ART initiation was not associated with retention in care and/or viral suppression throughout the first year on ART in unadjusted or adjusted analyses.
A substantial proportion of eligible pregnant women referred for ART do not begin treatment before delivery in this setting. Among women who do initiate ART, delaying initiation for patient preparation is not associated with improved maternal outcomes. Given the need to maximize the duration of ART before delivery for prevention of mother-to-child HIV transmission, there is an urgent need for new strategies to help expedite ART initiation in eligible pregnant women.
PMCID: PMC3490939  PMID: 22963318
Antiretroviral therapy; Pregnancy; Patient preparation; Prevention of mother-to-child transmission (PMTCT); HIV/AIDS; South Africa
19.  Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study 
PLoS Medicine  2012;9(9):e1001304.
Morna Cornell and colleagues investigate differences in mortality for HIV-positive men and women on antiretroviral therapy in South Africa.
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.
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.
Editors' Summary
About 34 million people (most living in low- and middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of becoming infected. Then, in 1996, antiretroviral therapy (ART)—cocktails of drugs that keep HIV in check—became available. For people living in affluent countries, HIV/AIDS became a chronic condition. However, ART was expensive and, for people living in poorer countries, HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global emergency, and governments and international agencies began to implement plans to increase ART coverage in resource-limited countries. Since then, ART programs in these countries have grown rapidly. In South Africa, for example, about 52% of the 3.14 million adults in need of ART were receiving an ART regimen recommended by the World Health Organization by the end of 2010.
Why Was This Study Done?
The outcomes of ART programs in resource-limited countries need to be evaluated thoroughly so that these programs can be optimized. One area of concern to ART providers is that of gender differences in survival among patients receiving treatment. In sub-Saharan Africa, for example, men are more likely to die than women while receiving ART. This gender difference in mortality may arise because men initiating ART in many African ART programs have more advanced HIV disease than women (early ART initiation is associated with better outcomes than late initiation) or because men are more likely to be lost to follow-up than women (failure to continue treatment is associated with death). Other possible explanations for gender differentials in mortality on ART include gender differences in immunologic and virologic responses to treatment (increased numbers of immune system cells and reduced amounts of virus in the blood, respectively). In this multicenter cohort study, the researchers examine the size of, and risk factors for, gender differences in mortality on ART in South Africa by examining data collected from adults starting ART at International Epidemiologic Databases to Evaluate AIDS South Africa (IeDEA-SA) collaboration sites.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 46,201 ART-naïve adults who started ART between 2002 and 2009 in eight IeDEA-SA ART programs. At ART initiation, men had a lower CD4 count on average and were more likely to have advanced HIV disease than women. During the study, after allowing for factors likely to affect mortality such as HIV disease stage at initiation, men on ART had a 31% higher risk of dying than women. Men were more likely to be lost to follow-up than women, but men and women who were lost to follow-up were equally likely to die. Women had a slightly better immunological response to ART than men but virologic suppression was similar in both genders. Importantly, in analyses of mortality limited to individuals who were virologically suppressed at 12 months and to patients who had a good immunological response to ART, men still had a higher risk of death than women. However, the gender differences in mortality on ART were smaller than the gender differences in age-standardized mortality in the HIV-negative South African population.
What Do These Findings Mean?
These analyses show that among South African patients initiating ART between 2002 and 2009, men were more likely to die than women but that this gender difference in mortality on ART cannot be completely explained by gender differences in baseline characteristics, loss to follow-up, or virologic and/or immunologic responses. Instead, the observed gender differences in mortality can best be explained by background gender differences in mortality in the whole South African population. Because substantial amounts of data were missing in this study (for example, HIV disease stage was not available for all the patients), these findings need to be interpreted cautiously. Moreover, similar studies need to be done in other settings to investigate whether they are generalizable to the South African national ART program and to other countries. If confirmed, however, these findings suggest that the root causes of gender differences in mortality on ART may be unrelated to HIV/AIDS or to the characteristics of ART programs.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information on the treatment of HIV/AIDS in South Africa is available from the Southern African HIV Clinicians Society
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV/AIDS treatment and care, and on HIV/AIDS in South Africa (in English and Spanish)
WHO provides information about universal access to AIDS treatment (in several languages); its 2010 ART guidelines can be downloaded
Information about the IeDEA-SA collaboration is available
The Treatment Action Campaign provides information on antiretroviral therapy and South African HIV statistics
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about taking anti-HIV drugs and the challenges of anti-HIV drugs
PMCID: PMC3433409  PMID: 22973181
20.  Maternal CD4+ Cell Count Decline after Interruption of Antiretroviral Prophylaxis for the Prevention of Mother-to-Child Transmission of HIV 
PLoS ONE  2012;7(8):e43750.
We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program.
Analysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm3 at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm3 or <200 cells/mm3 at 24 months. Weibull regression was used for multivariable analysis.
A total of 1,393 women with enrollment CD4+ ≥250 cells/mm3 initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23–30), median CD4+ was 469 cells/mm3 (IQR: 363–613). At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm3 was 12% (95% CI: 10–14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm3 was 28%; (95% CI: 25–32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm3: 46% (CD4+400–499 cells/mm3) vs. 19% (CD4+ ≥500 cells/mm3). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm3 within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5–3.2, p<0.0001).
Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.
PMCID: PMC3428298  PMID: 22952754
21.  Sexual health, HIV risk, and retention in an adolescent HIV prevention trial preparatory cohort 
Adolescents are at high risk for HIV infection, yet have not been included in HIV vaccine trials.
In preparation for their enrollment in HIV vaccine trials, 100 HIV-negative 14 to 17 year olds from Cape Town were recruited into a cohort. HIV, syphilis, pregnancy testing, and sexual risk questionnaires were performed at varying intervals for one year.
The mean age of the participants was 15 years, and 70% were female. Recruitment was completed in three months. Retention was 82% at 1 year. The main reasons for dropout were relocation to other communities, phlebotomy, and visit frequency. In a Cox proportional hazards model, only female gender was significantly associated with retention. No change in reported sexual risk occurred, but the proportion knowing their partners’ HIV status was significantly higher (17% at baseline, 83% at one year; p<0.001). There were five pregnancies during follow-up.
To our knowledge, this is the first prospective adolescent HIV prevention cohort in Southern Africa. Despite reports of risky sex and high pregnancy rates, HIV seroconversions did not occur in the retained cohort. HIV prevention trials with high-risk adolescents will require rigorous efforts to prevent pregnancy, and may require risk eligibility criteria. Retention may improve with transport provision, incentivizing visits, and efforts to retain males.
PMCID: PMC3124666  PMID: 21700155
Adolescents; HIV; sexual risk; retention; cohort
22.  Awareness and Interest in Intrauterine Contraceptive Device Use among HIV-Positive Women in Cape Town, South Africa 
Objective. To assess awareness of and interest in intrauterine contraceptive device (IUCD) use among HIV-positive women in Cape Town, South Africa. Design. Cross-sectional survey. Methods. HIV-positive women aged 18 through 45 years presenting for care at a primary health care clinic in Cape Town, South Africa participated in this study. Consented participants completed a staff-administered questionnaire in a private setting. Descriptive statistics were generated. Comparisons between demographic and reproductive health-related variables and IUCD awareness and interest were performed with multiple logistic regression. Analyses for IUCD interest excluded women with prior surgical sterilization. Results. Of 277 HIV-positive women, 37% were aware of the IUCD; awareness was independently associated with greater age (adjusted odds ratio (AOR) = 1.15, 95%; confidence interval (CI): 1.10–1.20) and not switching contraceptive methods in the last year (AOR = 2.45, 95% CI: 1.03–5.83). Following an IUCD information session, 86% of women (n = 206/240) were interested in IUCD use. IUCD interest was inversely associated with age (AOR = 0.91, 95% CI: 0.86–0.97) and marginally positively associated with current menstrual bleeding pattern complaints (AOR = 2.14, 95% CI: 0.98–4.68). Conclusions. Despite low levels of method awareness, HIV-positive women in this setting are frequently interested in IUCD use, indicating need for programming to expand method access.
PMCID: PMC3388580  PMID: 22778537
23.  Neuropsychological outcomes in adults commencing highly active anti-retroviral treatment in South Africa: a prospective study 
Infection with HIV may result in significant neuropsychological impairment, especially in late stage disease. To date, there have been no cohort studies of the impact of highly active anti-retroviral treatment (HAART) in South Africa where clade C HIV is predominant.
Participants in the current study were recruited from a larger study of HIV-associated neurocognitive disorders (HAND) and included a group of individuals commencing HAART (n = 82). Baseline and one-year neuropsychological function was assessed using a detailed battery, and summary global deficit scores (GDS) obtained. Associations with change in GDS were calculated.
Participants had a median CD4 cell count of 166 at baseline and 350 at follow-up. There were significant difference across groups of GDS severity at baseline with respect to level of education and GDS change at one year (p = 0.00 and 0.00 respectively). Participants with severe impairment at baseline improved significantly more than those with lesser degrees of impairment. Significant improvements were observed in the domains of attention, verbal fluency, motor function, and executive functions. There were unadjusted associations between GDS change and male gender, lower levels of education, baseline CD4 count and baseline GDS severity. In an adjusted model, only baseline GDS severity (p = 0.00) remained significant, with a lower level of education nearing significance (p = 0.05). The overall model was highly significant (p = 00; r-squared = 0.58).
In individuals in late stage HIV commencing HAART in South Africa, those with severe baseline neuropsychological impairment improved significantly more than those less impaired. While improvement across a number of neuropsychological domains was observed, high rates of impairment persisted.
The effects of HAART and participant variables, such as test experience, require clarification. Studies with larger comparison groups, and where HIV disease characteristics are needed to establish whether the trends we identified are clinically meaningful.
PMCID: PMC3356227  PMID: 22335937
HIV neuropsychology; Clade C; Combination anti-retroviral therapy; Neuropsychological outcomes
24.  Preventing Human Immunodeficiency Virus Infection Among Sexual Assault Survivors in Cape Town, South Africa: An Observational Study 
AIDS and Behavior  2011;16(4):990-998.
We describe 131 South African sexual assault survivors offered HIV post-exposure prophylaxis (PEP). While the median days completed was 27 (IQR 27, 28), 34% stopped PEP or missed doses. Controlling for baseline symptoms, PEP was not associated with symptoms (OR = 1.30, 95% CI = 0.66, 2.64). Factors associated with unprotected sex included prior unprotected sex (OR = 6.46, 95% CI = 3.04, 13.74), time since the assault (OR = 1.33, 95% CI = 1.12, 1.57) and age (OR = 1.30, 95% CI = 1.08, 1.57). Trauma counseling was protective (OR = 0.18, 95% CI = 0.05, 0.58). Four instances of seroconversion were observed by 6 months (risk = 3.7%, 95% CI = 1.0, 9.1). Proactive follow-up is necessary to increase the likelihood of PEP completion and address the mental health and HIV risk needs of survivors. Adherence interventions and targeted risk reduction counseling should be provided to minimize HIV acquisition.
PMCID: PMC3337999  PMID: 21301949
Human immunodeficiency virus; Post-exposure prophylaxis; Sexual assault; Adherence; Risk behavior

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