Asymptomatic parasitemia is common among schoolchildren living in areas of high malaria transmission, yet little is known about its effect on cognitive function in these settings. To investigate associations between asymptomatic parasitemia, anemia, and cognition among primary schoolchildren living in a high malaria transmission setting, we studied 740 children enrolled in a clinical trial in Tororo, Uganda. Parasitemia, measured by thick blood smears, was present in 30% of the children. Infected children had lower test scores for abstract reasoning (adjusted mean difference [AMD] −0.6, 95% confidence interval [CI] −1.01 to −0.21) and sustained attention (AMD −1.6 95% CI −2.40 to −0.81) compared with uninfected children. There was also evidence for a dose–response relationship between parasite density and scores for sustained attention. No associations were observed between anemia and either test of cognition. Schoolchildren in high transmission settings may experience cognitive benefits, from interventions aimed at reducing the prevalence of asymptomatic parasitemia.

Dihydroartemisinin-piperaquine administered at monthly intervals, but not that dosed once a school term, is a remarkably effective measure for the prevention of incidence of malaria, prevalence of parasitemia, and prevalence of anemia in schoolchildren living in a high-transmission setting.

Although recent data suggest high levels of adherence to expanding antiretroviral therapy (ART) programmes in resource-limited settings, the culture-specific barriers to adherence are poorly understood. In a prospective observational study, we found that 1.2% of patients discontinued ART because of a belief in spiritual healing. Spiritual beliefs should be an important part of ART adherence counselling in resource-limited settings, requiring close collaboration between HIV care programmes and religious leaders to identify common goals and ensure successful treatment.

Objective We evaluated the efficacy of a brief motivational intervention (MI) counseling in reducing alcohol consumption among persons living with HIV/AIDS (PLWHA) in Kampala-Uganda. Methods PLWHA attending an outpatient HIV clinic with alcohol disorders identification test-Consumption component (AUDIT-C) score ≥3 points were randomized to either standardized positive prevention counseling alone or in combination with alcohol brief MI counseling. Mean change in AUDIT-C scores over 6 months were compared by treatment arm. RESULTS The mean (SD) AUDIT-C scores were 6.3(2.3) and 6.8(2.3), for control and MI arms (p=0.1) at baseline and change in mean AUDIT-C score was not statistically different between the treatment arms over the 6 months follow up time (P=0.8). CONCLUSION There was a non-differential reduction in alcohol consumption in both intervention and control arms. Standard positive prevention counseling should be provided to all PLWHA who use alcohol. Studies with more than one counseling session need to be evaluated. Clinical trials.gov trial identifier: NCT01802736.

IntroductionAlcohol use by persons living with HIV/AIDS (PLWHA) negatively impacts the public health benefits of antiretroviral therapy (ART). Using a standardized alcohol assessment tool, we estimate the prevalence of alcohol use, identify associated factors, and test the association of alcohol misuse with sexual risk behaviors among PLWHA in Uganda.MethodsA cross-section of PLWHA in Kampala were interviewed regarding their sexual behavior and self-reported alcohol consumption in the previous 6 months. Alcohol use was assessed using the alcohol use disorders identification test (AUDIT). Gender-stratified log binomial regression analyses were used to identify independent factors associated with alcohol misuse and to test whether alcohol misuse was associated with risky sexual behaviors.ResultsOf the 725 subjects enrolled, 235 (33%) reported any alcohol use and 135 (18.6%) reported alcohol misuse, while 38 (5.2%) drank hazardous levels of alcohol. Alcohol misuse was more likely among subjects not yet on ART (adjusted prevalence ratio [aPR] was 1.65 p=0.043 for males and 1.79, p=0.019 for females) and those with self-reported poor adherence (aPR for males=1.56, p=0.052, and for females=1.93, p=0.0189). Belonging to Pentecostal or Muslim religious denominations was protective against alcohol misuse compared to belonging to Anglican and Catholic denominations in both sexes (aPR=0.11 for men, p<0.001, and aPR=0.32 for women, p=0.003). Alcohol misuse was independently associated with reporting risky sexual behaviors (aPR=1.67; 95% CI: 1.07–2.60, p=0.023) among males, but not significant among females (aPR=1.29; 95% CI: 0.95–1.74, p=0.098). Non-disclosure of HIV positive status to sexual partner was significantly associated with risky sex in both males (aPR=1.69; p=0.014) and females (aPR 2.45; p<0.001).ConclusionAlcohol use among PLWHA was high, and was associated with self-reported medication non-adherence, non-disclosure of HIV positive status to sexual partner(s), and risky sexual behaviors among male subjects. Interventions targeting alcohol use and the associated negative behaviors should be tested in this setting.

SummaryBackgroundCross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV.MethodsWe did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line ART had failed (assessed by WHO criteria with virological confirmation) were randomly assigned to a boosted protease inhibitor (standardised to ritonavir-boosted lopinavir) with two to three NRTIs (clinician-selected, without resistance testing); or with raltegravir; or alone as protease inhibitor monotherapy (discontinued after week 96). We tested genotypic resistance on stored baseline samples in patients in the protease inhibitor and NRTI group and calculated the predicted activity of prescribed second-line NRTIs. We measured viral load in stored samples for all patients obtained every 12–16 weeks. This trial is registered with Controlled-Trials.com (number ISRCTN 37737787) and ClinicalTrials.gov (number NCT00988039).FindingsBaseline genotypes were available in 391 (92%) of 426 patients in the protease inhibitor and NRTI group. 176 (89%) of 198 patients prescribed a protease inhibitor with no predicted-active NRTIs had viral suppression (viral load <400 copies per mL) at week 144, compared with 312 (81%) of 383 patients in the protease inhibitor and raltegravir group at week 144 (p=0·02) and 233 (61%) of 280 patients in the protease inhibitor monotherapy group at week 96 (p<0·0001). Compared with results with no active NRTIs, 95 (85%) of 112 patients with one predicted-active NRTI had viral suppression (p=0·3) and 20 (77%) of 26 patients with two or three active NRTIs had viral suppression (p=0·08). Over all follow-up, greater predicted NRTI activity was associated with worse viral load suppression (global p=0·0004).InterpretationGenotypic resistance testing might not accurately predict NRTI activity in protease inhibitor-based second-line ART. Our results do not support the introduction of routine resistance testing in ART programmes in low-income settings for the purpose of selecting second-line NRTIs.FundingEuropean and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Institito de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, WHO, Merck.

SummaryBackgroundMillions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings.MethodsWe analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787.FindingsBetween April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification.InterpretationProtease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings.FundingEuropean and Developing Countries Clinical Trials Partnership (...

BackgroundShort-medium term studies from sub-Saharan Africa show that, despite high early mortality, substantial loss to program, and high rates toxicity, patients on antiretroviral treatment have achieved outcomes comparable to those in developed settings. However, these studies were unable to account for long term outcomes of patients as they stayed longer on treatment.ObjectivesWe aim to describe ten years outcomes of one of the first cohort of HIV positive patients started on antiretroviral treatment (ART) in Sub-Saharan Africa.MethodsWe report 10-years outcomes including mortality, retention, CD4-count response, virological outcomes, ART regimens change from a prospective cohort of 559 patients initiating ART and followed up for 10 years Uganda.ResultsOf 559 patients, 69.1% were female, median age (IQR) was 38 (33–44) years, median CD4-count (IQR) 98 (21–163) cell/μL; 74% were started on stavudine, lamivudine and nevirapine, 26% on zidovudine, lamivudine and efavirenz. After 10 years 361 (65%) patients were still in the study; 127 (22.7%) had died; 30 (5%) were lost to follow-up; 27 (5%) transferred; 18 (3%) withdrew consent. The probability of death was high in the first year (0.15, 95%, CI 0.12–0.18). The median CD4 count increased from 98 to 589 cell/μL (IQR: 450–739 cell/μL) with a median increase of 357 cells/μL (IQR: 128–600 cells/μL); 7.4% never attained initial viral suppression and of those who did 31.7% experienced viral failure. Three hundred and two patients had at least one drug substitution while on first line after a median of 40 months; 66 (11.9%) of the patients were switched to a second line PI-based regimen due to confirmed treatment failure.ConclusionsDespite the high rate of early mortality due to advanced disease at presentation the outcomes from this cohort are encouraging, particularly the remarkable and incremental immune-recovery and a satisfactory rate of virologic suppression.