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.

IntroductionStable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.MethodsHIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24–36 months.ResultsFrom July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28–40) and (26–39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0–14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1–2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2–8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log10 copies/mL (IQR 3.31–4.53) and median CD4 count was 496 cells/µL (IQR 375–662); the majority (64%) had WHO stage 1 HIV-1 disease.ConclusionsCouples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245)

Aim-The World Health Organisation (WHO) haemoglobin colour scale has been developed as a simple, inexpensive clinical device for diagnosing anaemia when laboratory based haemoglobinometry is not available. In an initial validation study at several health centres, scale readings were compared with measurements of haemoglobin by the laboratory. This showed the scale to have 90% sensitivity and 70% specificity in identifying whether anaemia was present or not. In addition, when present, the degree of anaemia was correctly classified in clinical terms as moderate, pronounced, or severe, with an overall sensitivity of 60% and specificity of 88%. Errors were mainly marginal-that is, between two adjacent categories-but there were also some major discrepancies, such as a blood with a haemoglobin of 6-7 g/dl being read as normal or vice versa. Because this would compromise the scale's reliability in practice, this study was undertaken to identify the causes of the discrepancies and to reassess the performance of the scale. Methods-Venous blood samples were collected into potassium EDTA from patients attending selected clinics at three South African hospitals with good laboratory facilities. A prototype of the device was used unsupervised by nursing staV, doctors, and phlebotomists, who were told to follow the printed instructions. The blood specimens were then immediately sent to the laboratory where haemoglobin was measured by standardised automated blood cell counters. Any discrepancies > 1 g/dl were recorded and the tests were repeated by the same operators under supervision of the investigators. Results-Almost all the errors that occurred resulted from the incorrect use of the device, namely: inadequate or excessive blood, reading the results too soon or too late (beyond the limit of two minutes), poor lighting, or holding the scale at the wrong angle. The accuracy improved dramatically when the tests were repeated under supervision and these faults were avoided: 95% of readings were within 1 g/dl of the reference measurements, and 97% within 1.5 g/dl. Anaemia screening showed 96% sensitivity and 86% specificity. Clinical judgement of pallor was frequently wrong, whereas the scale gave the correct diagnosis in more than 97% of cases. Conclusion-The study confirmed the usefulness and reliability of the scale and its advantage over clinical signs for the diagnosis of anaemia, thus providing a clinically reliable near patient method in the absence of a laboratory. The instructions are easy to follow but must be strictly adhered to. (J Clin Pathol 2000;53:933-937)

BackgroundA pivotal phase III study of the RTS,S/AS01 malaria candidate vaccine is ongoing in several research centres across Africa. The development and establishment of quality systems was a requirement for trial conduct to meet international regulatory standards, as well as providing an important capacity strengthening opportunity for study centres.MethodsStandardized laboratory methods and quality assurance processes were implemented at each of the study centres, facilitated by funding partners.ResultsA robust protocol for determination of parasite density based on actual blood cell counts was set up in accordance with World Health Organization recommendations. Automated equipment including haematology and biochemistry analyzers were put in place with standard methods for bedside testing of glycaemia, base excess and lactacidaemia. Facilities for X-rays and basic microbiology testing were also provided or upgraded alongside health care infrastructure in some centres. External quality assurance assessment of all major laboratory methods was established and method qualification by each laboratory demonstrated. The resulting capacity strengthening has ensured laboratory evaluations are conducted locally to the high standards required in clinical trials.ConclusionMajor efforts by study centres, together with support from collaborating parties, have allowed standardized methods and robust quality assurance processes to be put in place for the phase III evaluation of the RTS, S/AS01 malaria candidate vaccine. Extensive training programmes, coupled with continuous commitment from research centre staff, have been the key elements behind the successful implementation of quality processes. It is expected these activities will culminate in healthcare benefits for the subjects and communities participating in these trials.Trial registrationClinicaltrials.gov NCT00866619