Summary Background Expanded access to combination antiretroviral therapy (ART) in the resource-poor setting is dependent on “task-shifting” from doctors to other health care providers. We compared “doctor-initiated-nurse-monitored” care to the current standard of care, “doctor-initiated-doctor-monitored” ART. Methods A randomised strategy trial to determine whether treatment outcomes of “nurse-monitored” ART were non-inferior to “doctor-monitored” ART was conducted at two South African primary-care clinics. HIV-positive individuals with a CD4 count of <350cells/mm3 or WHO stage 3 or 4 disease were eligible. The primary objective was a composite end-point of treatment limiting events, incorporating mortality, viral failure, treatment-limiting toxicities and visit schedule adherence. Intention-to-treat analyses were performed. This study is registered with ClinicalTrials.gov, NCT00255840. Findings The hazard ratio for composite failure was 1.09 (95% CI= 0.89-1.33) which lay within the limits for non-inferiority. The analysis was performed on 812 HIV-positive adults with either doctor-(n=408) or nurse-monitored ART (n=404). At baseline 573 (70%) patients were female, 282 (34.7%) had prior AIDS diagnoses and the median CD4 was 164 cells/mm3. After a median follow-up of 24.3 months, deaths (10 vs. 11), virological failures (44 vs. 39), CD4 gain (270 vs. 248 cells/mm3), toxicity failures (68 vs. 66) and program losses (70 vs. 63) were similar in nurse and doctor arms respectively. 371(46%) patients reached an endpoint of treatment failure; 192(47.5%) and 179(43.9%) in the nurse and doctor arms respectively. Interpretation Nurse-monitored ART was shown to be non-inferior to doctor-monitored therapy. This study supports task-shifting to appropriately trained nurses for monitoring ART.

BackgroundAntiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART.MethodologyData on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis.FindingsOnly 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period.ConclusionLinkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.

Objective To investigate antiretroviral treatment (ART) interruption in a long-term treatment cohort in South Africa. Methods All adults accessing ART between 2004 and 2009 were included in this analysis. Defaulting was defined as having stopped all ART drugs for more than 30 days. Treatment interrupters were patients who defaulted and returned to care during the study, whereas loss to follow-up was defined as defaulting and not returning to care. Kaplan-Meier estimates and Possion regression models were used to analyze rates and determinants of defaulting therapy and of treatment resumption. Results Overall rate of defaulting treatment was 12.8/100 person years (95% CI 11.4-14.4). Risk factors for defaulting were male gender, high baseline CD4 count, recency of ART initiation and time on ART. The probability of resuming therapy within 3 years of defaulting therapy was 42% (event rate=21.4/100 person-years). Factors associated with restarting treatment were female gender, older age, and time since defaulting. Conclusion Defaulting treatment need not be an irreversible event. Interventions to increase retention in care should target men, less immunocompromised patients and patients during the first 6 months of treatment. Resumption of treatment is most likely within the first year of interrupting therapy.

Introduction Increasing EFV dose from 600mg to 800mg daily has been suggested with concomitant RFN, as induction of cytochrome p450 isoenzymes may reduce EFV plasma concentrations Methods Individuals from the CIPRA-South Africa cohort taking EFV-based ART with concomitant TB were dosed with either increased-(800mg) or standard-(600mg) dose EFV during TB treatment. After TB therapy all took 600mg EFV. Two mid-dosing interval EFV concentrations were determined from each individual: after 4 weeks of concomitant EFV and RFN therapy, and at least 4 weeks after TB therapy completion. Mid-dosing interval EFV concentrations were compared within individuals using the Wilcoxon signed rank test. Results Paired-samples were collected from 72 individuals. 45(63%) were women; median weight 59kg (IQR52-67kg). At ART start median CD4 count was114 cells/mm3 (IQR37-165), median viral load 5.5log (IQR5.1–5.9). 38 (53%) took 800mg EFV during TB treatment and 34(47%) took 600mg. EFV concentrations in the 800mg group were higher with RFN [[2.9mg/L (IQR 1.8–5.6)] than without [2.1mg/L (IQR 1.4–3.0)]], p=0.0003. There was no significant difference in EFV concentrations with RFN [2.4mg/L (IQR1.2–5.1)] or without [2.2 mg/L (IQR 1.4 to 3.7)] in the 600mg group. There was no increase in EFV-linked adverse effects in either group. Proportion virologically suppressed at 48 weeks was similar in both groups. Conclusion EFV concentrations were significantly increased in the EFV 800mg group on RFN. There was no significant decrease in EFV concentrations when on RFN in the 600mg group. Dose escalation of EFV 600mg to 800mg is not required during concomitant TB therapy in South Africa.