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1.  Treatment Outcomes of HIV-Infected Adolescents Attending Public-Sector HIV Clinics Across Gauteng and Mpumalanga, South Africa 
There is little evidence comparing treatment outcomes between adolescents and other age groups, particularly in resource-limited settings. A retrospective analysis of data from seven HIV clinics across urban Gauteng (n=5) and rural Mpumalanga (n=2), South Africa was conducted. The analysis compared HIV-positive antiretroviral treatment (ART)-naive young adolescents (10–14 years), older adolescents (15–19), and young adults (20–24 years) to adults (≥25 years) initiated onto standard first-line ART between April 2004 and August 2010. Log-binomial regression was used to estimate relative risk (RR) of failure to suppress viral load (≥400 copies/ml) or failure to achieve an adequate CD4 response at 6 or 12 months. The effect of age group on virological failure, mortality, and loss to follow-up (LTFU; ≥90 days since scheduled visit date) was estimated using Cox proportional hazards models. Of 42,427 patients initiating ART, 310 (0.7%) were young adolescents, 342 (0.8%) were older adolescents, and 1599 (3.8%) were young adults. Adolescents were similar to adults in terms of proportion male, baseline CD4 count, hemoglobin, and TB. Compared to adults, both older adolescents (6 months RR 1.75 95% CI 1.25–2.47) and young adults (6 months RR 1.33 95% CI 1.10–1.60 and 12 months RR 1.64 95% CI 1.23–2.19) were more likely to have an unsuppressed viral load and were more likely to fail virologically (HR 2.90 95% CI 1.74–4.86; HR 2.94 95% CI 1.63–5.31). Among those that died or were LTFU, the median time from ART initiation until death or LTFU was 4.7 months (IQR 1.5–13.2) and 10.9 months (IQR 5.0–22.7), respectively. There was no difference in risk of mortality by age category, compared to adults. Young adolescents were less likely to be LTFU at any time period after ART initiation (HR 0.43 95% CI 0.26–0.69) whereas older adolescents and young adults were more likely to be LTFU after ART initiation (HR 1.78 95% CI 1.34–2.36; HR 1.63 95% CI 1.41–1.89) compared to adults. HIV-infected adolescents and young adults between 15 and 24 years have poorer ART treatment outcomes in terms of virological response, LTFU, and virological failure than adults receiving ART. Interventions are needed to help improve outcomes and retention in care in this unique population.
PMCID: PMC3653371  PMID: 23373540
2.  The Feasibility of Using Screening Criteria to Reduce Clinic Visits for Stable Patients on Antiretroviral Therapy in South Africa 
South African HIV care providers are exploring ways to reduce the intensity of patient visits while maintaining high quality of care. We used routinely collected data to model whether a simple screening tool could identify stable patients who would not need to see a doctor during a scheduled medical visit.
We identified stable and non-stable visits from January 2007 to September 2011 at a large HIV clinic in Johannesburg, SA. Stable medical visits were defined as having all of the following: stable CD4 count, undetectable viral load, stable weight, not pregnant, no comorbidity, no regimen change within three months, and normal lab results for hemoglobin, ALT, and creatinine clearance.
We assessed the sensitivity and specificity of non-stable visits at predicting indicators of disease progression or needing additional care: a) ART regimen change; and b) follow-up visits in <2 and <4 weeks from previous visit.
Stable visits had a sensitivity of 88.9% (95% CI 88.2–89.7) and a specificity of 44.8% (44.5–44.1) at predicting ART therapy changes, and a sensitivity of 72.6% (71.8–73.4) and specificity of 45.1% (44.8–45.4) for predicting a follow-up visit interval of <2 weeks and similar results for predicting a follow-up visit interval of <4 weeks.
Our retrospective analysis suggests an approach to potentially reduce the number of medical visits while missing few visits in which changes in regimen or additional care would be needed. Evaluation of our criteria in a primary care setting is needed to determine whether they could safely reduce visits.
PMCID: PMC3619021  PMID: 23111577
3.  Outcomes of stable HIV-positive patients down-referred from doctor-managed ART clinics to nurse-managed primary health clinics for monitoring and treatment 
AIDS (London, England)  2011;25(16):10.1097/QAD.0b013e32834b6480.
Compare clinical, immunologic and virologic outcomes amongst stable HIV-positive patients down-referred (DR) to nurse-managed primary health care clinic (PHC) for treatment maintenance to those who remained at the doctor-managed treatment-initiation site (TI).
We conducted a matched cohort analysis amongst stable HIV patients at the Themba Lethu Clinic, in Johannesburg, South Africa. Eligible patients met the criteria for down-referral (undetectable viral load <10-months, ART >11-months, CD4 ≥200cells/mm3, stable weight and no opportunistic infections) regardless of whether they were down-referred to a PHC for treatment maintenance between February 2008-January 2009. Patients were matched 1:3 (DR:TI) using propensity scores.
We calculated rates and hazard ratios for the effect of down-referral on loss to follow-up (LTFU) and mortality and the relative risk of down-referral on viral rebound by 12-months of follow-up.
693 DR patients were matched to 2079 TI patients. Two (0.3%) DR and 32 (1.5%) TI patients died, 10 (1.4%) DR and 87 (4.2%) TI were lost, while 22 (3.3%) DR and 100 (5.6%) TI experience viral rebound by 12-months of follow-up. After adjustment, patients down-referred were less likely to die (HR 0.2; 95%CI: 0.04-0.8), become LTFU (HR 0.3; 95%CI: 0.2-0.6) or experience viral rebound (RR 0.6; 95%CI 0.4-0.9) than TI patients during follow-up.
The utilization of nurse-managed PHCs for treatment maintenance of stable patients could decrease the burden on specialized doctor-managed ART clinics. Patient outcomes for DR patients at PHCs appear equal, if not better, than those achieved at ART clinics amongst stable patients.
PMCID: PMC3669640  PMID: 21997488
antiretroviral therapy; task-shifting; nurse-managed vs. doctor-managed care; mortality; loss to follow-up; resource-limited setting; scaling-up
4.  Incidence of Pregnancy after Initiation of Antiretroviral Therapy in South Africa: A Retrospective Clinical Cohort Analysis 
Background. Little is known about rates of incident pregnancy among HIV-positive women initiating highly active antiretroviral therapy (HAART). Methods. We conducted a retrospective clinical cohort study among therapy-naïve women ages 18–45 initiating HAART between 1 April 2004 and 30 September 2009 at an adult HAART clinic in Johannesburg, South Africa. We used Poisson regression to characterize rates and rate ratios of pregnancy. Results. We evaluated 5,996 women who experienced 727 pregnancies during 14,095 person-years at risk. The overall rate of pregnancy was 5.2 per 100 person-years (95% confidence limits [CL] 4.8, 5.5). By six years, cumulative incidence of first pregnancy was 22.9% (95% CL 20.6%, 25.4%); among women ages 18–25 at HAART initiation, cumulative incidence was 52.2% (95% CL 35.0%, 71.8%). The strongest predictor of incidence of pregnancy was age, with women 18–25 having 13.2 times the rate of pregnancy of women ages 40–45 in adjusted analysis. CD4 counts below 100 and worse adherence to HAART were associated with lower rates of incident pregnancy. Conclusions. Women experience high rates of incident pregnancy after HAART initiation. Understanding which women are most likely to experience pregnancy will help planning and future efforts to understand the implications of pregnancy for response to HAART.
PMCID: PMC3388336  PMID: 22778536
5.  Treatment Outcomes and Cost-Effectiveness of Shifting Management of Stable ART Patients to Nurses in South Africa: An Observational Cohort 
PLoS Medicine  2011;8(7):e1001055.
Lawrence Long and colleagues report that “down-referring” stable HIV patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health facility provides good health outcomes and cost-effective treatment for patients.
To address human resource and infrastructure shortages, resource-constrained countries are being encouraged to shift HIV care to lesser trained care providers and lower level health care facilities. This study evaluated the cost-effectiveness of down-referring stable antiretroviral therapy (ART) patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health care facility in Johannesburg, South Africa.
Methods and Findings
Criteria for down-referral were stable ART (≥11 mo), undetectable viral load within the previous 10 mo, CD4>200 cells/mm3, <5% weight loss over the last three visits, and no opportunistic infections. All patients down-referred from the treatment-initiation site to the down-referral site between 1 February 2008 and 1 January 2009 were compared to a matched sample of patients eligible for down-referral but not down-referred. Outcomes were assigned based on vital and health status 12 mo after down-referral eligibility and the average cost per outcome estimated from patient medical record data.
The down-referral site (n = 712) experienced less death and loss to follow up than the treatment-initiation site (n = 2,136) (1.7% versus 6.2%, relative risk = 0.27, 95% CI 0.15–0.49). The average cost per patient-year for those in care and responding at 12 mo was US$492 for down-referred patients and US$551 for patients remaining at the treatment-initiation site (p<0.0001), a savings of 11%. Down-referral was the cost-effective strategy for eligible patients.
Twelve-month outcomes of stable ART patients who are down-referred to a primary health clinic are as good as, or better than, the outcomes of similar patients who are maintained at a hospital-based ART clinic. The cost of treatment with down-referral is lower across all outcomes and would save 11% for patients who remain in care and respond to treatment. These results suggest that this strategy would increase treatment capacity and conserve resources without compromising patient outcomes.
Please see later in the article for the Editors' Summary
Editors' Summary
AIDS has killed more than 25 million people since 1981, and about 33 million people are now infected with HIV, the virus that causes AIDS. Because HIV destroys immune system cells, which leaves infected individuals susceptible to other infections, early in the AIDS epidemic, most HIV-infected people died within ten years of infection. Then, in 1996, antiretroviral therapy (ART), which can keep HIV in check for many years, became available. For people living in developed countries, HIV infection became a chronic condition, but people in developing countries were not so lucky—ART was prohibitively expensive and so a diagnosis of HIV infection remained a death sentence in many regions of the world. In 2003, this situation was declared a global health emergency, and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. As a result, nowadays, more than a third of people in low- and middle-income countries who need ART are receiving it.
Why Was This Study Done?
Unfortunately, shortages of human resources in developing countries are impeding progress toward universal ART coverage. In sub-Saharan Africa, for example, where two-thirds of all HIV-positive people live, there are too few doctors to supervise all the ART that is required. Various organizations are therefore encouraging a shift of clinical care responsibilities for people receiving ART from doctors to less highly trained, less expensive, and more numerous members of the clinical workforce. Thus, in South Africa, plans are underway to reduce the role of hospital doctors in ART and to increase the role of primary health clinic nurses. One specific strategy involves “down-referring” patients whose HIV infection is under control (“stable ART patients”) from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health care facility. In this observational study, the researchers investigate the effect of this strategy on treatment outcomes and costs by retrospectively analyzing data collected from a cohort (group) of adult patients initially treated by doctors at the Themba Lethu Clinic in Johannesburg and then down-referred to a nearby primary health clinic where nurses supervised their treatment.
What Did the Researchers Do and Find?
Patients attending the hospital-based ART clinic were invited to transfer to the down-referral site if they had been on ART for at least 11 months and met criteria that indicated that ART was controlling their HIV infection. Each of the 712 stable ART patients who agreed to be down-referred to the primary health clinic was matched to three patients eligible for down-referral but not down-referred (2,136 patients), and clinical outcomes and costs in the patient groups were compared 12 months after down-referral eligibility. At this time point, 1.7% of the down-referred patients had died or had been lost to follow up compared to 6.2% of the patients who continued to receive hospital-based ART. The average cost per patient-year for those in care and responding at 12 months was US$492 for down-referred patients but US$551 for patients remaining at the hospital. Finally, the down-referral site spent US$509 to produce a patient who was in care and responding one year after down-referral on average, whereas the hospital spent US$602 for each responding patient. Thus, the down-referral strategy (nurse-managed care) was more cost-effective than continued hospital treatment (doctor-managed care).
What Do These Findings Mean?
These findings indicate that, at least for this pair of study sites, the 12-month outcomes of stable ART patients who were down-referred to a primary health clinic were as good as or better than the outcomes of similar patients who remained at a hospital-based ART clinic. Moreover, the down-referral strategy saved 11% of costs for patients who remained in care and responded to treatment and appeared to be cost-effective, although additional studies are needed to confirm this last finding. Because this is an observational study (that is, patients eligible for down-referral were not randomly assigned to hospital or primary care facility treatment), it is possible that some unknown factor was responsible for the difference in outcomes between the two patient groups. Nevertheless, these results suggest that the down-referral strategy tested in this study could increase ART capacity and conserve resources without compromising patient outcomes in South Africa and possibly in other resource-limited settings.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Ford and Mills
The US National Institute of Allergy and Infectious Diseases provides information on HIV infection and AIDS
HIV InSite has comprehensive information on HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment, including its 2010 progress report (in English, French and Spanish)
Right to Care, a non-profit organization that aims to deliver and support quality clinical services in Southern Africa for the prevention, treatment, and management of HIV, provides information on down-referral
PMCID: PMC3139666  PMID: 21811402

Results 1-5 (5)