Background HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004–2013. Methods Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. Findings Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine VL, 1·21 (1·13–1·30) for targeted VL and 0·49 (0·43–0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114–133 cells/µl). Interpretation Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

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HAART-treated ADC patients with baseline CSF markers of viral and immunologic inactivity did not necessarily have inactive ADC when followed over 12 weeks. More sensitive CSF markers to judge the activity of ADC are urgently needed, whereas the interpretation of these markers should be considered with caution in HAART-treated ADC patients.

Objectives:To determine the efficacy of adding abacavir (Ziagen, ABC) to optimal stable background antiretroviral therapy (SBG) to AIDS dementia complex (ADC) patients and address trial design.Design:Phase III randomized, double-blind placebo-controlled trial.Setting:Tertiary outpatient clinics.Participants:ADC patients on SBG for ≥8 wk.Interventions:Participants were randomized to ABC or matched placebo for 12 wk.Outcome Measures:The primary outcome measure was the change in the summary neuropsychological Z score (NPZ). Secondary measures were HIV RNA and the immune activation markers β-2 microglobulin, soluble tumor necrosis factor (TNF) receptor 2, and quinolinic acid.Results:105 participants were enrolled. The median change in NPZ at week 12 was +0.76 for the ABC + SBG and +0.63 for the SBG groups (p = 0.735). The lack of efficacy was unlikely related to possible limited antiviral efficacy of ABC: at week 12 more ABC than placebo participants had plasma HIV RNA ≤400 copies/mL (p = 0.002). There were, however, other factors. Two thirds of patients were subsequently found to have had baseline resistance to ABC. Second, there was an unanticipated beneficial effect of SBG that extended beyond 8 wk to 5 mo, thereby rendering some of the patients at baseline unstable. Third, there was an unexpectedly large variability in neuropsychological performance that underpowered the study. Fourth, there was a relative lack of activity of ADC: 56% of all patients had baseline cerebrospinal fluid (CSF) HIV-1 RNA <100 copies/mL and 83% had CSF β-2 microglobulin <3 nmol/L at baseline.Conclusions:The addition of ABC to SBG for ADC patients was not efficacious, possibly because of the inefficacy of ABC per se, baseline drug resistance, prolonged benefit from existing therapy, difficulties with sample size calculations, and lack of disease activity. Assessment of these trial design factors is critical in the design of future ADC trials.

Compressive prestress effects on the electrical and mechanical properties of relaxor ferroelectric materials were studied as a function of temperature for several formulations of Pb(Mg1/3Nb2/3)O3‐PbTiO3‐BaTiO3 (PMN‐PT‐BT) ceramics. Experimentally measured polarization and strain, induced by an ac electric field, decreased as compressive stress increased. Effective Young's moduli also were measured under constant dc electric fields. A significant decrease in modulus was observed with increasing field. The prestress and modulus experiments were modeled analytically using a proposed relaxor ferroelectric constitutive law. In general, excellent agreement between the model and experiments was obtained, indicating that the model accurately predicted the coupled behavior of this relaxor ferroelectric material.