The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.

Matthias Egger and colleagues present a nomogram and a web-based calculator to correct estimates of program-level mortality for loss to follow-up, for use in antiretroviral treatment programs.

Summaryobjective To estimate the rates of mortality in patients lost to follow-up (LTFU) from a large urban public sector HIV clinic in South Africa.methods We compared vital status using the clinic's database to vital status verified against the Vital Registration system at the South African Department of Home Affairs. We compared rates of mortality before and after updating mortality data. Predictors of mortality were estimated using Kaplan-Meier curves and proportional hazard regression.results Of the 7097 total patients who initiated highly active antiretroviral therapy at Themba Lethu Clinic by October 1st, 2008 and had an ID number, 6205 were included. 2453 patients (21%) were LTFU, of whom 1037 (42.3%) could be included in the analysis. After matching to the vital registration system, mortality more than doubled from 4.2% (258 ⁄ 6205) to 10.9% (676 ⁄ 6205). Overall 37% of those LTFU died by life-table analysis the probability of survival amongst those LTFU was 69% (95% CI: 66-72%), 64% (95% CI: 61-67%) and 59% (95% CI: 55-62%) by years 1, 2 and 3 since being lost, respectively. Those at highest risk of death after being lost were patients with a history of tuberculosis, CD4 count < 100 cells ⁄ ll, BMI < 17.5, haemoglobin < 10 and on <6 months of treatment.

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Background In high-income countries viral load (VL) is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. VL monitoring is not generally available in resource-limited settings. We examined switching from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor (PI)-based regimens in Africa, South America and Asia. Design and methods Multi-cohort study of 17 ART programmes. All sites monitored CD4 counts and had access to second-line ART, 10 sites monitored VL. We compared times to switching, CD4 counts at switching and obtained adjusted hazard ratios for switching (aHR) with 95% confidence intervals (CIs) from random-effects Weibull models. Results A total of 20,113 patients, including 6,369 (31.7%) patients from 10 programmes with access to VL monitoring were analysed; 576 patients (2.9%) switched. Low CD4 counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months (interquartile range [IQR] 10.1–26.6) in programmes with VL and 21.8 months (IQR 14.0–21.8) in programmes without VL monitoring (p<0.001). Median CD4 cell counts at switching were 161 cells/μl (IQR 77–265) and 102 cells/μl (44–181), respectively (p<0.001). Switching was more common in programmes with VL monitoring during months 7–18 after starting ART (aHR 1.38; 95% CI 0.97–1.98), similar during months 19–30 (aHR 0.97; 0.58–1.60) and less common during months 31–42 (aHR 0.29; 0.11–0.79). Conclusions In resource-limited settings switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with VL monitoring compared to programmes without VL monitoring.

Summaryobjective To assess the outcome of patients who experienced treatment failure with antiretrovirals in sub-Saharan Africa.methods Analysis of 11 antiretroviral therapy (ART) programmes in sub-Saharan Africa. World Health Organization (WHO) criteria were used to define treatment failure. All ART-naive patients aged ‡16 who started with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen and had at least 6 months of follow-up were eligible. For each patient who switched to a second-line regimen, 10 matched patients who remained on a non-failing first-line regimen were selected. Time was measured from the time of switching, from the corresponding time in matched patients, or from the time of treatment failure in patients who remained on a failing regimen. Mortality was analysed using KaplanMeier curves and random-effects Cox models.results Of 16 591 adult patients starting ART, 382 patients (2.3%) switched to a second-line regimen. Another 323 patients (1.9%) did not switch despite developing immunological or virological failure. Cumulative mortality at 1 year was 4.2% (95% CI 2.2-7.8%) in patients who switched to a second-line regimen and 11.7% (7.3%-18.5%) in patients who remained on a failing first-line regimen, compared to 2.2% (1.6-3.0%) in patients on a non-failing first-line regimen (P < 0.0001). Differences in mortality were not explained by nadir CD4 cell count, age or differential loss to follow up.conclusions Many patients who meet criteria for treatment failure do not switch to a second-line regimen and die. There is an urgent need to clarify the reasons why in sub-Saharan Africa many patients remain on failing first-line ART.

Objective 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). Design 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. Methods 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. Results 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. Conclusions 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.

Summary OBJECTIVES To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment. METHODS Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/μl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements ≥10 0000 copies/ml (higher threshold) or ≥500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated. RESULTS A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6–33.6%) for the higher and 12.6% (6.7–21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3–97.8%) and 97.3% (96.5–98.0%), for positive predictive value 9.5% (3.6–19.6%) and 19.0% (10.2–30.9%) and for negative predictive value 98.5% (97.9–99.0%) and 95.7% (94.7–96.6%). CONCLUSIONS The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.