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1.  Sexual behaviour in a rural high HIV prevalence South African community: time trends in the antiretroviral treatment era 
AIDS (London, England)  2013;27(15):2461-2470.
Objectives
Data from generalized epidemic settings have consistently found that patients on antiretroviral therapy (ART) reduce sexual risk behaviours, but how sexual behaviour changes in the general population in response to ART availability, including amongst HIV-uninfected and undiagnosed adults, has not been characterized in these settings.
Design
General population open cohort.
Methods
We report trends in sexual behaviour indicators for men aged 17–54 years and women aged 17–49 years in rural KwaZulu-Natal province, based on annual sexual behaviour surveys during ART scale-up from 2005 to 2011. Estimates are adjusted for survey non-participation and non-response to individual survey items using inverse probability weighting and multiple imputation. Trends are presented by HIV status, knowledge of status, age and marital status.
Results
Reports of condom use at last sex with a regular partner increased by 2.6% points per year [95% confidence interval (CI) 1.5%, 3.7%] for men and 4.1% per year (3.0%, 5.3%) for women. Condom use at last sex with a casual partner was high and did not change significantly over the period for both sexes. There were statistically significant declines in the percentage reporting multiple partnerships in the last year and the point prevalence of concurrency. Trends within subgroups are generally consistent with overall estimates.
Conclusion
We find no evidence of increased sexual risk-taking following ART availability and protective changes in some behaviours, suggesting that general trends in sexual behaviour are not counter-acting preventive effects of HIV treatment. Continued monitoring of population-level sexual behaviour indicators will be essential to interpret the success of combination-prevention programmes.
doi:10.1097/01.aids.0000432473.69250.19
PMCID: PMC3773237  PMID: 23842132
Africa; antiretroviral therapy; HIV; sexual behaviour; trends
2.  Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment 
Science (New York, N.Y.)  2013;339(6122):10.1126/science.1230413.
The scale-up of antiretroviral therapy (ART) is expected to raise adult life expectancy in populations with high HIV prevalence. Using data from a population cohort of over 101,000 individuals in rural KwaZulu-Natal, South Africa, we measured changes in adult life expectancy for 2000–2011. In 2003, the year before ART became available in the public sector health system, adult life expectancy was 49.2 years; by 2011, adult life expectancy had increased to 60.5 years – an 11.3-year gain. Based on standard monetary valuation of life, the survival benefits of ART far outweigh the costs of providing treatment in this community. These gains in adult life expectancy signify the social value of ART and have implications for investment decisions of individuals, governments, and donors.
doi:10.1126/science.1230413
PMCID: PMC3860268  PMID: 23430655
3.  The Association between Self-Reported Stigma and Loss-to-Follow Up in Treatment Eligible HIV Positive Adults in Rural Kwazulu-Natal, South Africa 
PLoS ONE  2014;9(2):e88235.
Background
The relationship between loss-to-follow-up (LTFU) in HIV treatment and care programmes and psychosocial factors, including self-reported stigma, is important to understand. This prospective cohort study explored stigma and LTFU in treatment eligible adults who had yet not started antiretroviral therapy (ART).
Methods
Psychosocial, clinical and demographic data were collected at a baseline interview. Self-reported stigma was measured with a multi-item scale. LTFU was defined as not attending clinic in the 90 days since last appointment or before death. Data was collected between January 2009 and January 2013 and analysed using Cox Regression.
Results
380 individuals were recruited (median time in study 3.35 years, total time at risk 1065.81 person-years). 203 were retained (53.4%), 109 were LTFU (28.7%), 48 had died and were not LTFU at death (12.6%) and 20 had transferred out (5.3%). The LTFU rate was 10.65 per 100 person-years (95% CI: 8.48–12.34). 362 individuals (95.3%) started ART. Stigma total score (categorised in quartiles) was not significantly associated with LTFU in either univariable or multivariable analysis (adjusting for other variables in the final model): second quartile aHR 0.77 (95%CI: 0.41–1.46), third quartile aHR 1.20(95%CI: 0.721–2.04), fourth quartile aHR 0.62 (95%CI: 0.35–1.11). In the final multivariable model, higher LTFU rates were associated with male gender, increased openness with friends/family and believing that community problems would be solved at higher levels. Lower LTFU rates were independently associated with increased year of age, greater reliance on family/friends, and having children.
Conclusions
Demographic and other psychosocial factors were more closely related to LTFU than self-reported stigma. This may be consistent with high levels of social exposure to HIV and ART and with stigma affecting LTFU less than other stages of care. Research and clinical implications are discussed.
doi:10.1371/journal.pone.0088235
PMCID: PMC3930529  PMID: 24586310
4.  Patient satisfaction with HIV and TB treatment in a public programme in rural KwaZulu-Natal: evidence from patient-exit interviews 
Background
Patient satisfaction is a determinant of treatment uptake, adherence and retention, and an important health systems outcome. Queues, health worker-patient contact time, staff attitudes, and facility cleanliness may affect patient satisfaction. We quantified dimensions of patient satisfaction among HIV and TB patients in a rural sub-district of KwaZulu-Natal, South Africa, and identified underlying satisfaction factors that explained the data.
Methods
We conducted patient-exit interviews with 300 HIV and 300 TB patients who were randomly selected using a two-stage cluster random sampling approach with primary sampling units (primary healthcare clinics) selected with probability-proportional-to-size sampling. We performed factor analysis to investigate underlying patient satisfaction factors. We compared the satisfaction with HIV and TB services and examined the relationships between patient satisfaction and patients’ socio-demographic characteristics in multivariable regression.
Results
Almost all patients (95% HIV, 97% TB) reported to be globally satisfied with the healthcare services received on the day of the interview. However, patient satisfaction with specific concrete aspects of the health services was substantially lower: 52% of HIV and 40% of TB patients agreed that some staff did not treat patients with sufficient respect (p = 0.02 for difference between the two patient groups); 65% of HIV and 40% of TB patients agreed that health worker queues were too long (p < 0.001). Based on factor analysis, we identified five factors underlying the HIV data and the TB data (availability, accommodation, acceptability and communication for HIV and TB patients; health worker preference for HIV patients only; and global satisfaction for TB patients only). The level of satisfaction did not vary significantly with patients’ socio-demographic characteristics.
Conclusions
In this rural area, HIV and TB patients’ evaluations of specific aspects of health services delivery revealed substantial dissatisfaction hidden in the global assessments of satisfaction. A wide range of patient satisfaction variables could be reduced to a few underlying factors that align broadly with concepts previously identified in the literature as affecting access to healthcare. Increases in health systems resources for HIV and TB, but also improvements in facility maintenance, staff attitudes and communication, are likely to substantially improve HIV and TB patients’ satisfaction with the care they receive in public-sector treatment programmes in rural communities in South Africa.
doi:10.1186/1472-6963-14-32
PMCID: PMC3904687  PMID: 24450409
Patient satisfaction; Factor analysis; HIV; TB; Health systems
5.  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/μL 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-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/μL over the first six years, increasing marginally to 145 cells/μL in 2010/11 and more significantly to 199 cells/μL in 2011/12. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate 19.4 per 100 person-years (95% confidence interval (CI) 18.2-20.7). After adjustment for sex, age, baseline CD4+ cell count and concurrent TB, there was a 46% decrease in early mortality for those who initiated ART in 2011/12 compared to the reference period 2008/9 (sub-hazard ratio 0.54, 95% CI 0.41-0.71).
Conclusions
Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rates 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.
doi:10.1097/QAI.0b013e31829ceb14
PMCID: PMC3867341  PMID: 23756374
HIV-1; anti-retroviral agents; CD4 lymphocyte count; mortality; access to health care
6.  Ageing with HIV in South Africa 
AIDS (London, England)  2011;25(13):10.1097/QAD.0b013e32834982ea.
We used an established microsimulation model, quantified to a rural South African setting with a well-developed antiretroviral treatment program, to predict the impact of antiretroviral therapy on the HIV epidemic in the population aged 50+. We show that the HIV prevalence in patients aged 50+ will nearly double in the next 30 years, while the fraction of HIV infected patients aged over 50 will triple in the same period. This ageing epidemic has important consequences for the South African health-care system, as older HIV patients require specialized care.
doi:10.1097/QAD.0b013e32834982ea
PMCID: PMC3886337  PMID: 21681056
HIV; Antiretroviral therapy; Ageing; Mathematical model; Epidemiological trends
7.  The impact of antiretroviral treatment on the age composition of the HIV epidemic in sub-Saharan Africa 
AIDS (London, England)  2012;26(0 1):10.1097/QAD.0b013e3283558526.
Introduction
Antiretroviral treatment (ART) coverage is rapidly expanding in sub-Saharan Africa (SSA). Based on the effect of ART on survival of HIV-infected people and HIV transmission the age composition of the HIV epidemic in the region is expected to change in the coming decades. We quantify the change of the age composition of HIV-infected people in all countries in SSA.
Methods
We used STDSIM, a stochastic microsimulation model, and developed an approach to represent HIV prevalence and treatment coverage in 43 countries in SSA, using publicly available data. We predict future trends in HIV prevalence and total number of infections among the populations aged 15-49 and 50 years and older (50+) for different ART coverage levels.
Results
We show that, if treatment coverage continues to increase at present rates, the total number of HIV-infected patients aged 50+ will nearly triple over the coming years: from 3.1 million in 2011 to 9.1 million in 2040, dramatically changing the age composition of the HIV epidemic in SSA. In 2011, about 1 in 7 HIV-infected people was aged 50 years or older; in 2040, this ratio will be larger than 1 in 4.
Conclusion
The HIV epidemic in SSA is rapidly ageing, implying changing needs and demands in many social sectors, including health, social care, and old-age pension systems. Health policymakers need to anticipate the impact of the changing HIV age composition in their planning for future capacity in these systems.
doi:10.1097/QAD.0b013e3283558526
PMCID: PMC3886374  PMID: 22781175
HIV; Antiretroviral therapy; Ageing; Mathematical model; Epidemiological trends
8.  Is the Risk of HIV Acquisition Increased during and Immediately after Pregnancy? A Secondary Analysis of Pooled HIV Community-Based Studies from the ALPHA Network 
PLoS ONE  2013;8(12):e82219.
Background
Previous studies of HIV acquisition in pregnancy have been in specific population groups, such as sero-discordant couples which have shown an increased risk of HIV acquisition during pregnancy and studies of sexually active women where the results have been ambiguous. However these studies are unable to tell us what the overall impact of pregnancy is on HIV acquisition in the general population.
Methods
Data from six community-based HIV cohorts were pooled to give 2,628 sero-conversions and a total of 178,000 person years of observation. Multiple imputation was used to allow for the uncertainty of exact sero-conversion date in surveillance intervals greater than the length of a pregnancy. Results were combined using Rubin’s rules to give appropriate error bounds. The analysis was stratified into two periods: pre- and post- widespread availability of prevention of mother-to-child HIV transmission services. This allows us to assess whether there is reporting bias relating to a person’s knowledge of their own HIV status which would become more widespread in the latter time period.
Results
Results suggest that women while pregnant have a lower risk of acquiring HIV infection over all periods (HRR 0.79, 95%CI 0.70-0.89) than women who were not pregnant. There is no evidence for a difference in the rate of HIV acquisition between postpartum and non-pregnant women (HRR 0.92 95%CI 0.84-1.03).
Discussion
Although there may be immunological reasons for increased risk of HIV acquisition during pregnancy, at a population level this study indicates a lower risk of HIV acquisition for pregnant women. Pregnant women may be more likely to be concordant with their current sexual partner than non-pregnant women, i.e. either already HIV positive prior to the pregnancy or if negative at the time of becoming pregnant more likely to have a negative partner.
doi:10.1371/journal.pone.0082219
PMCID: PMC3873249  PMID: 24386091
9.  Mortality in women of reproductive age in rural South Africa 
Global Health Action  2013;6:10.3402/gha.v6i0.22834.
Objective
To determine causes of death and associated risk factors in women of reproductive age in rural South Africa.
Methods
Deaths and person-years of observation (pyo) were determined for females (aged 15–49 years) resident in 15,526 households in a rural South African Demographic and Health Surveillance site from 2000 to 2009. Cause of death was ascertained by verbal autopsy and ICD-10 coded; causes were categorized as HIV/TB, non-communicable, communicable/maternal/perinatal/nutrition, injuries, and undetermined (unknown). Characteristics of women were obtained from regularly updated household visits, while HIV and self-reported health status was obtained from the annual HIV surveillance. Overall and cause-specific mortality rates (MRs) with 95% confidence intervals (CI) were calculated. The Weibull regression model (HR, 95% CI) was used to determine risk factors associated with mortality.
Results
A total of 42,703 eligible women were included; 3,098 deaths were reported for 212,607 pyo. Overall MRwas 14.6 deaths/1,000 pyo (95% CI: 14.1–15.1), peaking in 2003 (MR 18.2/1,000 pyo, 95% CI: 16.4–20.1) and declining thereafter (2009: MR 9.6/1,000 pyo, 95% CI: 8.4–10.9). Mortality was highest for HIV/TB (MR 10.6/1,000 pyo, 95% CI: 10.2–11.1), accounting for 73.1% of all deaths, ranging from 61.2% in 2009 to 82.7% in 2002. Adjusting for education level, marital status, age, employment status, area of residence, and migration, all-cause mortality was associated with external migration (adjusted hazard ratio, or aHR), 1.70, 95% CI: 1.41–2.05), self-reported poor health status (aHR 8.26, 95% CI: 2.94–23.15), and HIV-infection (aHR 7.84, 95% CI: 6.26–9.82); external migration and HIV infection were also associated with causes of mortality other than HIV/TB (aHR 1.62, 95% CI: 1.12–2.34 and aHR 2.59, 95% CI: 1.79–3.75).
Conclusion
HIV/TB was the leading cause of death among women of reproductive age, although rates declined with the rollout of HIV treatment in the area from 2004. Women's age, external migration status and HIV-positive status were significantly associated with all-cause and cause-specific mortality.
doi:10.3402/gha.v6i0.22834
PMCID: PMC3869952  PMID: 24360403
reproductive age; women; mortality; rural South Africa; risk factors
10.  Exclusive Breastfeeding, Diarrhoeal Morbidity and All-Cause Mortality in Infants of HIV-Infected and HIV Uninfected Mothers: An Intervention Cohort Study in KwaZulu Natal, South Africa 
PLoS ONE  2013;8(12):e81307.
Introduction
Antiretroviral drug interventions significantly reduce the risk of HIV transmission to infants through breastfeeding. We report diarrhoea prevalence and all-cause mortality at 12 months of age according to infant feeding practices, among infants born to HIV-infected and uninfected mothers in South Africa.
Methods
A non-randomised intervention cohort study that followed both HIV-infected and HIV-uninfected mothers and their infants until 18 months of age. Mothers were supported in their infant feeding choice. Detailed morbidity and vital status data were collected over the first year. At the time, only single dose nevirapine was available to prevent mother-to-child transmission of HIV.
Results
Among 2,589 infants, detailed feeding data and vital status were available for 1,082 HIV-exposed infants and 1,155 HIV non-exposed infants. Among exclusively breastfed (EBF) infants there were 9.4 diarrhoeal days per 1,000 child days (95%CI. 9.12-9.82) while among infants who were never breastfed there were 15.6 diarrhoeal days per 1,000 child days (95%CI. 14.62-16.59). Exclusive breastfeeding was associated with fewer acute, persistent and total diarrhoeal events than mixed or no breastfeeding in both HIV-exposed infants and also infants of HIV uninfected mothers. In an adjusted cox regression analysis, the risk of death among all infants by 12 months of age was significantly greater in those who were never breastfed (aHR 3.5, p<0.001) or mixed fed (aHR 2.65, p<0.001) compared with those who were EBF. In separate multivariable analyses, infants who were EBF for shorter durations had an increased risk of death compared to those EBF for 5-6 months [aHR 2.18 (95% CI, 1.56-3.01); p<0.001].
Discussion
In the context of antiretroviral drugs being scaled-up to eliminate new HIV infections among children, there is strong justification for financial and human resource investment to promote and support exclusive breastfeeding to improve HIV-free survival of HIV-exposed and non-exposed infants.
doi:10.1371/journal.pone.0081307
PMCID: PMC3846835  PMID: 24312545
11.  Nearly Full Employment Recovery Among South African HIV Patients On Antiretroviral Therapy: Evidence From A Large Population Cohort 
Health affairs (Project Hope)  2012;31(7):10.1377/hlthaff.2012.0407.
Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the U.S. President’s Emergency Plan for AIDS Relief. We linked clinical data from more than 2000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of over 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening illness and the decision to seek care. We find large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss.
doi:10.1377/hlthaff.2012.0407
PMCID: PMC3819460  PMID: 22778335
12.  Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries 
BMC Infectious Diseases  2013;13:522.
Background
Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common.
Methods
Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12–24 months after delivery (n = 1070). Women with a CD4 count of 200-500cells/mm3 and gestational age 28–36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: <200 cells/mm3 initiated antiretroviral therapy, and >500 cells/mm3 received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin < 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models.
Results
At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥6 months) and shorter ARV exposure. Severe anaemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1–2 months of ARV’s, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort.
Conclusions
Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring.
Trial registration number
ISRCTN71468401
doi:10.1186/1471-2334-13-522
PMCID: PMC3829097  PMID: 24192332
Zidovudine; Pregnancy; HIV; Sub-Saharan Africa; Anaemia; Drug toxicity
13.  Elimination of HIV in South Africa through Expanded Access to Antiretroviral Therapy: A Model Comparison Study 
PLoS Medicine  2013;10(10):e1001534.
Using nine structurally different models, Jan Hontelez and colleagues investigate timeframes for HIV elimination in South Africa using a universal test and treat strategy.
Please see later in the article for the Editors' Summary
Background
Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV.
Methods and Findings
We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled.
Conclusions
Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 34 million people (mostly in low- and middle-income countries) are currently infected with HIV, the virus that causes AIDS, and every year another 2.5 million people become infected. HIV, which is usually transmitted through unprotected sex with an infected partner, gradually destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, people infected with HIV often died within ten years of infection. Then, in 1996, antiretroviral therapy (ART) became available, and, for people living in affluent countries, HIV/AIDS became a chronic condition. However, ART was expensive, so HIV/AIDS remained a fatal condition for people living in resource-limited countries. In 2006, the international community set a target of achieving universal ART coverage by 2010, and ART programs were initiated in many resource-limited countries. Although universal ART coverage has still not been achieved in South Africa, where nearly 6 million people are HIV-positive, 80% of people in need of ART were receiving a World Health Organization–recommended ART regimen by October 2012.
Why Was This Study Done?
ART is usually started when a person's CD4 count falls below 350 cells/µl blood, but it is thought that treatment of all HIV-positive individuals, regardless of their CD4 count, could reduce HIV transmission by reducing the infectiousness of HIV-positive individuals (“treatment as prevention”). Might it be possible, therefore, to eliminate HIV by screening everyone annually for infection and treating all HIV-positive individuals immediately? In 2009, a mathematical modeling study suggested that seven years of universal test and treat (UTT) could eliminate HIV in South Africa. The deterministic (nonrandom) model used in that study has been widely criticized, however, and some subsequent modeling studies have reached different conclusions, probably because of differences in the models' structures and in the assumptions built into them. A better understanding of the reasons for the discrepancies between models would help policy-makers decide whether to introduce UTT, so, here, the researchers developed several increasingly complex and realistic models of the South African HIV epidemic and used these models to predict the long-term impact of UTT in South Africa.
What Did the Researchers Do and Find?
The researchers developed nine structurally different mathematical models of the South African HIV epidemic based on the STDSIM framework, a stochastic microsimulation model that simulates the life course of individuals in a dynamic network of sexual contacts and in which events such as HIV infection are random processes. The simplest model, which resembled the original deterministic model, was extended by sequentially adding in factors such as different HIV transmission rates at different stages of HIV infection and up-to-date assumptions regarding the ability of ART to reduce HIV infectiousness. All the models replicated the prevalence of HIV in South Africa (the proportion of the population that was HIV-positive) between 1990 and 2010, and all predicted that UTT (defined as annual screening of individuals age 15+ years and immediate ART for all HIV-infected adults starting in 2012 and scaled up to 90% coverage by 2019) would result in HIV elimination (less than one new infection per 1,000 person-years). However, whereas the simplest model predicted that UTT would eliminate HIV after seven years, the more complex, realistic models predicted elimination at much later time points. Importantly, the most comprehensive model predicted that, although elimination would be reached after about 17 years of UTT, the current strategy of ART initiation for HIV-positive individuals at a CD4 cell count at or below 350 cells/µl would also lead to HIV elimination, albeit ten years later than UTT.
What Do These Findings Mean?
These findings confirm previous predictions that UTT could eliminate HIV in South Africa, but the development of more realistic models than those used in the past suggests that HIV elimination would occur substantially later than originally predicted. Importantly, the most comprehensive model suggests that HIV could be eliminated in South Africa using the current strategy for ART treatment alone. As with all modeling studies, the accuracy of these findings depends on the assumptions built into the models and on the structure of the models. Thus, although these findings support the use of UTT as an intervention to eliminate HIV, more research with comprehensive models that incorporate factors such as data from ongoing trials of treatment as prevention is needed to determine the population-level impact and overall cost-effectiveness of UTT.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001534.
This study is further discussed in a PLOS Medicine Perspective by Ford and Hirnschall
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
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 and AIDS in South Africa, on HIV treatment as prevention and the possibility of HIV elimination (in English and Spanish)
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
The World Health Organization provides information about universal access to AIDS treatment (in several languages); its 2010 ART guidelines can be downloaded
The PLOS Medicine Collection Investigating the Impact of Treatment on New HIV Infections provides more information about HIV treatment as prevention
Personal stories about living with HIV/AIDS are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001534
PMCID: PMC3805487  PMID: 24167449
14.  Decreased Chronic Morbidity but Elevated HIV Associated Cytokine Levels in HIV-Infected Older Adults Receiving HIV Treatment: Benefit of Enhanced Access to Care? 
PLoS ONE  2013;8(10):e77379.
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 (>1.56pg/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(>1ug/mL); ART-naïve HIV-infected individuals had >double apPOR of having hsCRP levels indicative of increased heart disease risk(>3.9ug/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.
doi:10.1371/journal.pone.0077379
PMCID: PMC3797035  PMID: 24143226
15.  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 <0.001). There was a strong association between disengagement from care and higher baseline CD4+ cell count (subhazard ratio (SHR) 1.94 (P < 0.001) and 2.35 (P < 0.001) for CD4+ cell count 150–200 cells/μl and >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.
doi:10.1111/tmi.12135
PMCID: PMC3775257  PMID: 23731253
HIV-1; antiretroviral agents; primary health care; delivery of health care; lost to follow-up; disengagement from care
16.  Sexual risk after HIV diagnosis: a comparison of pre-ART individuals with CD4>500 cells/µl and ART-eligible individuals in a HIV treatment and care programme in rural KwaZulu-Natal, South Africa 
Introduction
Little is known about people diagnosed as HIV-positive who access HIV care early in their disease. In pre-ART studies published to date, only a minority of the participants have CD4>500 cells/µl.
Methods
This cross-sectional study compared individuals presenting for HIV care with CD4>500 cells/µl, “pre-ART” (N=247), with individuals who had CD4<200 cells/µl or WHO Stage IV, “ART-eligible” (N=385). Baseline characteristics were contrasted between the two groups and logistic regression models used to explore group differences in: (a) being sexually active in the last month; (b) disclosure of HIV status to current partner; (c) knowing the HIV status of one's current partner; and (d) condom use at last sex.
Results
Pre-ART and ART-eligible individuals were similar in terms of a wide range of socio-demographic characteristics. Controlling for gender, only current sexual behaviour and HIV-testing history were significantly different between ART groups. In multivariable models, participants in the pre-ART group were twice as likely to be sexually active in the last month, OR 2.06 95% CI (1.32, 3.21), and to know their partner's status, OR 1.95 (1.18, 3.22) compared to those in the ART-eligible group. Self-reported disclosure of HIV status to current sexual partner (71%), condom use at last sex (61%) and HIV concordancy within relationships were not significantly different between the two ART groups. Overall, 39% of the study participants reported knowing that they were in concordant HIV-positive relationships. Fifty-five percent of all participants reported not knowing their partner's HIV status, only half of whom reported using a condom at last sex. Pre-ART individuals were significantly less likely to have tested HIV-positive for the first time in the last year and to have tested for sickness-related reasons than the ART-eligible group.
Conclusions
Reported sexual risk behaviours by pre-ART individuals with CD4>500 cells/µl suggest a continued risk of onward HIV transmission. There is a need for positive prevention efforts to target this group given that current treatment guidelines do not provide them with ART. Strengthening support regarding disclosure, partner HIV testing and consistent condom use, and further promotion of HIV testing in the community to assist earlier diagnosis are urgently required.
doi:10.7448/IAS.16.1.18048
PMCID: PMC3736456  PMID: 23920209
AIDS; antiretroviral therapy; HIV; sexual risk behaviours; ART-eligible; pre-ART
17.  Unpacking the recommended indicator for concurrent sexual partnerships 
AIDS (London, England)  2012;26(8):1037-1039.
Summary
Using sexual behaviour survey data, we examine the methodological choice for the time period underlying the UNAIDS Reference Group recommended ‘point prevalence’ indicator for concurrency. Results confirm that 6 months before the interview is a good time point for calculating the recommended indicator, and that this retrospective estimate is substantially lower than the estimate of concurrency based on the number of current partnerships. The discrepancy is only partially explained by disproportionate missing data in those with more sexual partners.
doi:10.1097/QAD.0b013e328351f726
PMCID: PMC3725702  PMID: 22313959
18.  Collective patient behaviours derailing ART roll-out in KwaZulu-Natal: perspectives of health care providers 
Background
Antiretroviral therapy (ART) roll-out is fraught with challenges, many with serious repercussions. We explored and described patient behaviour-related challenges from the perspective of health care providers from non-governmental organisations involved in ART programmes in KwaZulu-Natal, South Africa.
Methods
A descriptive case study design using qualitative approach was applied during this study. Data was collected from nine key informants from the three biggest NGOs involved in ART roll-out using in-depth semi-structured interviews. Transcribing and coding for emergent themes was done by two independent reviewers. Ethical approval for the study was granted by the UNISA research ethics committee of The Faculty of Health Sciences. Written consent was obtained from directors of the three NGOs involved and individual audio taped informed consent was obtained from all study participants prior to data collection.
Results
Findings revealed six broad areas of patient behaviour challenges. These were patient behaviour related to socio-economic situation of patient (skipping of medication due to lack of food, or due to lack of transport fees), belief systems (traditional and religious), stigma (non- disclosure), sexual practices (non-acceptability of condoms, teenage pregnancies), escapism (drug and alcohol abuse) and opportunism (skipping medication in order to access disability grant, teenage pregnancies in order to access child grant).
Conclusion
New programmes need to address patient behaviour as a complex phenomenon requiring a multi-pronged approach that also addresses social norms and institutions. In the face of continued ART scale up, this is further evidence for the need for multi-sectoral collaboration to ensure successful and sustainable ART roll-out.
doi:10.1186/1742-6405-10-20
PMCID: PMC3765690  PMID: 23870285
Patient behaviour; ART roll-out; Health care provider perspective; Non-governmental organisation; KwaZulu-Natal
19.  Impact of a novel molecular TB diagnostic system in patients at high risk of TB mortality in rural South Africa (Uchwepheshe): study protocol for a cluster randomised trial 
Trials  2013;14:170.
Background
Tuberculosis control in sub-Saharan Africa has long been hampered by poor diagnostics and weak health systems. New molecular diagnostics, such as the Xpert® MTB/RIF assay, have the potential to improve patient outcomes. We present a cluster randomised trial designed to evaluate whether the positioning of this diagnostic system within the health system has an impact on important patient-level outcomes.
Methods/Design
This pragmatic cluster randomised clinical trial compared two positioning strategies for the Xpert MTB/RIF system: centralised laboratory versus primary health care clinic. The cluster (unit of randomisation) is a 2-week time block at the trial clinic. Adult pulmonary tuberculosis suspects with confirmed human immunodeficiency virus infection and/or at high risk of multidrug-resistant tuberculosis are enrolled from the primary health care clinic. The primary outcome measure is the proportion of culture-confirmed pulmonary tuberculosis cases initiated on appropriate treatment within 30 days of initial clinic visit. Univariate logistic regression will be performed as the primary analysis using generalised estimating equations with a binomial distribution function and a logit link.
Conclusion
Diagnostic research tends to focus only on performance of diagnostic tests rather than on patient-important outcomes. This trial has been designed to improve the quality of evidence around diagnostic strategies and to inform the scale-up of new tuberculosis diagnostics within public health systems in high-burden settings.
Trial registration
Current Controlled Trials ISRCTN18642314; South African National Clinical Trials Registry DOH-27-0711-3568.
doi:10.1186/1745-6215-14-170
PMCID: PMC3686680  PMID: 23758662
Tuberculosis; Multidrug-resistant tuberculosis; HIV; Molecular diagnostics; Point-of-care systems; Clinical trial
20.  Detection of antenatal depression in rural HIV-affected populations with short and ultrashort versions of the Edinburgh Postnatal Depression Scale (EPDS) 
Risk of antenatal depression has been shown to be elevated in Southern Africa and can impact maternal and child outcomes, especially in the context of the Human Immunodeficiency Virus (HIV). Brief screening methods may optimize access to care during pregnancy, particularly where resources are scarce. This research evaluated shorter versions of the Edinburgh Postnatal Depression Scale (EPDS) to detect antenatal depression. This cross-sectional study at a large primary health care (PHC) facility recruited a consecutive series of 109 antenatal attendees in rural South Africa. Women were in the second half of pregnancy and completed the EPDS and Structured Clinical Interview for Depression (SCID). The recommended EPDS cutoff (≥13) was used to determine probable depression. Four versions, including the 10-item scale, seven-item depression, and novel three- and five-item versions developed through regression analysis, were evaluated using receiver operating characteristic (ROC) analysis. High numbers of women 51/109 (47 %) were depressed, most depression was chronic, and nearly half of the women were HIV positive 49/109 (45 %). The novel three-item version had improved positive predictive value (PPV) over the 10-item version and equivalent specificity to the seven-item depression subscale; the novel five-item provided the best overall performance in terms of ROC and Cronbach's reliability statistics and had improved specificity. The brevity, sensitivity, and reliability of the short and ultrashort versions could facilitate widespread community screening. The usefulness of the novel three- and five-item versions are underscored by the fact that sensitivity is important at first screening, while specificity becomes more important at higher levels of care. Replication in larger samples is required.
doi:10.1007/s00737-013-0353-z
PMCID: PMC3778840  PMID: 23615932
Antenatal depression; Screening; EPDS; Short; Ultrashort; HIV
21.  Health, wellbeing, and disability among older people infected or affected by HIV in Uganda and South Africa 
Global Health Action  2013;6:10.3402/gha.v6i0.19201.
Objective
To describe and compare the health status, emotional wellbeing, and functional status of older people in Uganda and South Africa who are HIV infected or affected by HIV in their families.
Methods
Data came from the general population cohort and Entebbe cohort of the Medical Research Council/Uganda Virus Research Institute, and from the Africa Centre Demographic Information System through cross-sectional surveys in 2009/10 using instruments adapted from the World Health Organization (WHO) Study on Global Ageing and adult health (SAGE). Analysis was based on 932 people aged 50 years or older (510 Uganda, 422 South Africa).
Results
Participants in South Africa were slightly younger (median age − 60 years in South Africa, 63 in Uganda), and more were currently married, had no formal education, were not working, and were residing in a rural area. Adjusting for socio-demographic factors, older people in South Africa were significantly less likely to have good functional ability [adjusted odds ratio (aOR) 0.72, 95% CI 0.53–0.98] than those in Uganda, but were more likely to be in good subjective wellbeing (aOR 2.15, 95% CI 1.60–2.90). South Africans were more likely to be obese (aOR 5.26, 95% CI 3.46–8.00) or to be diagnosed with hypertension (aOR 2.77, 95% CI 2.06–3.73).
Discussion and conclusions
While older people’s health problems are similar in the two countries, marked socio-demographic differences influence the extent to which older people are affected by poorer health. It is therefore imperative when designing policies to improve the health and wellbeing of older people in sub-Saharan Africa that the region is not treated as a homogenous entity.
doi:10.3402/gha.v6i0.19201
PMCID: PMC3554811  PMID: 23364075
South Africa; Uganda; older people; health status; functional ability; subjective wellbeing
22.  Predictors of pregnancy and changes in pregnancy incidence among HIV-positive women accessing HIV clinical care at 13 large UK clinics 
AIDS (London, England)  2013;27(1):95-103.
Objectives
To describe predictors of pregnancy and changes in pregnancy incidence among HIV-positive women accessing HIV clinical care.
Methods
Data were obtained through the linkage of two separate studies; the UK Collaborative HIV Cohort study (UK CHIC), a cohort of adults attending 13 large HIV clinics, and the National Study of HIV in Pregnancy and Childhood (NSHPC), a national surveillance study of HIV-positive pregnant women. Pregnancy incidence was measured using the proportion of women in UK CHIC with a pregnancy reported to NSHPC. Generalised estimating equations were used to identify predictors of pregnancy and assess changes in pregnancy incidence in 2000-2009.
Results
The number of women accessing care at UK CHIC sites increased as did the number of pregnancies (from 72 to 230). Older women were less likely to have a pregnancy (adjusted Relative Rate (aRR) 0.44 per 10 year increment in age [95% CI [0.41-0.46], p<0.001) as were women with CD4<200 cells/mm3 compared with CD4 200-350 cells/mm3 (aRR 0.65 [0.55-0.77] p<0.001) and women of white ethnicity compared with women of black-African ethnicity (aRR 0.67 [0.57-0.80], p<0.001). The likelihood that women had a pregnancy increased over the study period (aRR 1.05 [1.03-1.07], p<0.001). The rate of change did not significantly differ according to age group, ART use, CD4 group or ethnicity.
Conclusions
The pregnancy rate among women accessing HIV clinical care increased in 2000-2009. HIV-positive women with, or planning, a pregnancy require a high level of care and this is likely to continue and increase as more women of older age have pregnancies.
doi:10.1097/QAD.0b013e3283565df1
PMCID: PMC3495056  PMID: 22713479
HIV; pregnancy; pregnancy rate; maternal age; highly active antiretroviral therapy; maternal-fetal infection transmission; United Kingdom
23.  The social dynamics of consent and refusal in HIV surveillance in rural South Africa 
Social Science & Medicine (1982)  2013;77(C):118-125.
In the context of low rates of participation in a prospective, population-based HIV surveillance programme, researchers at a surveillance site in rural KwaZulu-Natal, South Africa, conducted an operational study from January 2009 to February 2010, with the aim of improving participation rates, particularly in the provision of dried blood spots for the surveillance. Findings suggest, firstly, that consent to participation in the HIV surveillance is informed by the dynamics of relationality in the HIV surveillance “consent encounter.”
Secondly, it emerged that both fieldworkers and participants found it difficult to differentiate between HIV surveillance and HIV testing in the surveillance procedure, and tended to understand and explain giving blood under the aegis of the surveillance as an HIV test. The conflation of surveillance and testing, we argue, is not merely a semantic confusion, but reveals an important tension inherent to global health research between individual risks and benefits and collective good, or between private morality and public good. Because of these structural tensions, we suggest, the HIV surveillance consent encounter activates multiple gift economies in the collection of blood samples. Thinking beyond the complex ethical dimensions provoked by new forms of long-term surveillance and health research, we therefore suggest that deepening relations between scientists, fieldworkers, and study participants in locality deserve more careful methodological consideration and descriptive attention.
Highlights
► Consent and refusal to HIV surveillance take place in the context of everyday social relations and local exchange economies. ► Local notions of gift and relatedness and rights and obligations frame exchanges of blood for knowledge in HIV surveillance. ► Participants struggled to differentiate HIV surveillance from testing, thereby blurring concepts of risk and benefit. ► Surveillance programs should engage with local constructions of risk, benefit and relatedness in research design.
doi:10.1016/j.socscimed.2012.11.015
PMCID: PMC3560061  PMID: 23219165
South Africa; Ethics; Surveillance research; Obligation and reciprocity; Kinship; Local relations; HIV testing; Participation
24.  Why MSM in Rural South African Communities Should be an HIV Prevention Research Priority 
AIDS and Behavior  2012;17(Suppl 1):70-76.
Research into HIV and men who have sex with men’s (MSM) health in South Africa has been largely confined to the metropolitan centres. Only two studies were located making reference to MSM in rural contexts or same-sex behaviors among men in the same. There is growing recognition in South Africa that MSM are not only disproportionately affected by HIV and have been underserved by the country’s national response, but that they contribute significantly to sustaining the high number of new infections recorded each year. We argue that to meet the objectives of the country’s national strategic plan for HIV, STI and TB it is important we know how these behaviours may be contributing to the sustained rural HIV epidemic in the youngest age groups and determine what constitutes appropriate and feasible programmatic response that can be implemented in the country’s public sector health services.
doi:10.1007/s10461-012-0356-1
PMCID: PMC3627851  PMID: 23196857
Rural; MSM; HIV prevention; Research; South Africa
25.  Human resources needs for universal access to antiretroviral therapy in South Africa: a time and motion study 
Background
Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs) required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria.
Methods
We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year.
Results
For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/μl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR), equivalent to US$ 141 million. For universal treatment (‘treatment as prevention’), an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million).
Conclusions
Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/μl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments.
doi:10.1186/1478-4491-10-39
PMCID: PMC3529683  PMID: 23110724
Human resources for health; HIV; South Africa; Antiretroviral treatment

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