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 (...

Background: Hepatitis B Virus (HBV) infection is an important occupational health risk among primary healthcare providers (PHCPs). However, there is limited evidence on whether PHCPs’ level of knowledge and attitude can predict better HBV infection prevention practices. This study established the relationship between knowledge, attitude, and HBV infection prevention practices among PHCPs in Wakiso district, Central Uganda. Methods: A cross-sectional study design was used. Data were collected from 306 PHCPs, using a structured questionnaire. PHCPs were randomly selected from 55 healthcare facilities. STATA version 14.0 was used to analyse data. A ‘modified Poisson’ regression model was used for inferential statistics. Results: About 42.2% of PHCPs exhibited poor knowledge of HBV infection transmission and prevention, 41.8% had a negative attitude, and 41.5% exhibited poor prevention practices. Age (PR 1.82, 95% CI: 1.24–2.66) was positively associated with the level of knowledge. Healthcare facility level (PR 0.53, 95% CI: 0.34–0.84), main department of work (PR 0.69, 95% CI: 0.51–0.95), years in service (PR 0.66, 95% CI: 0.44–0.99), working in private not-for-profit healthcare facilities (PR 0.59, 95% CI: 0.34–0.99), and public healthcare facilities (PR 0.58, 95% CI: 0.42–0.80) were negatively associated with the level of knowledge. There was a negative association between the location of healthcare facility (PR 0.76, 95% CI: 0.62–0.93) and attitude, and a positive association between level of knowledge (PR 1.36, 95% 1.12–1.65) and attitude. Working in a public healthcare facility (PR 0.80, 95% CI: 0.64–0.99) was negatively associated with practices while having a positive attitude (PR 1.60, 95% CI: 1.28–1.99) predicted better HBV infection prevention practices. Conclusion: PHCPs who were more knowledgeable about HBV infection were more likely to have a positive attitude. In turn, having a positive attitude was associated with better HBV infection prevention practices. There is a need to sensitise PHCPs on HBV infection, and provision of screening and vaccination services in order to address the KAP gaps.

Background: There is some evidence that patients with liver diseases commonly use complementary and alternative therapies to address general and liver-disease specific health concerns. The purpose of this study was to assess and describe prevalence, patterns and related factors of herbal medicine use among adults diagnosed with viral and non-viral hepatitis in Kampala, Uganda. Methods: A cross-sectional study was conducted on 310 adult patients attending the gastrointestinal clinic in Mulago hospital referral hospital in Kampala. Data on prevalence, types and reasons for herbal medicine use was collected using standardized questionnaires and focus group discussions. Modified Poisson regression analyses were used to examine factors related to use. Results: Usage of various herbal remedies within 12 months prior to April 2018 was reported by 46.1% (143/310) of patients with 27.3% (39/143) of these reporting having used conventional and herbal therapies concurrently. Herbal remedies were used to treat various health conditions including hepatitis. Patients with hepatitis C virus infection (PRR = 1.16, p = 0.02) compared to those with hepatitis B virus infection, and those who believed that it was safe to use herbal and conventional therapies concurrently (PRR = 1.23, p = 0.008) had higher prevalence odds of herbal medicine use. Conversely, patients who had been newly diagnosed with hepatitis (PRR = 0.69, p = 0.03) compared to those who had been diagnosed more than one-year prior, had lower prevalence odds of herbal medicine use. Various types of local herbs were reported as most commonly used however most patients did not know the ingredients of commercially prepared herbal therapies. Conclusion: A high prevalence of herbal medicine use was found among newly-diagnosed patients and patients with hepatitis C more likely to use herbal remedies after adjusting for other factors. Usage was influenced by the belief that herbal medicine is safe and effective. Health workers need to consistently elicit information about herbal remedy use. Research is needed on benefits, adverse effects and outcomes in patients who use herbal remedies to treat primary liver diseases in order to facilitate evidence of efficacy and product safety.

Background Despite of the global efforts undertaken to improve nutrition, malnutrition still continues to be a serious public health concern. Malnutrition in its various forms has been closely associated to major causes of illness, disability and death. Malnutrition in the form of childhood stunting has therefore been identified as a significant hindrance to human development. The aim of this study was to assess the nutritional status of children aged 6–59 months and determine factors associated with a high prevalence of stunting (48%) among children in Kabale district. Methodology A cross sectional study was conducted among 640 children, aged 6–59 months selected using both simple random and systematic random sampling techniques. Interview administered questionnaires were used to collect household data whereas anthropometric data was collected using height boards, digital weighing scales and Mid Upper Arm Circumference (MUAC) Tapes. Nutrition status data was analyzed using ENA for SMART, 2011 and then exported to STATA version 12.0 for further analysis. Results The overall prevalence of stunting among children 6–59 months was 41.1%. Factors independently associated with stunting included; age of the child (children in the age category of 36-47 months APOR = 0.38; 95% CI 0.18–0.79 and those in the age category of 24-35 months APOR = 0.42; 95% CI 0.19–0.88), major source of food for the household that is children from households in which mothers indicated market as the major source of food (APOR = 0.67; 95% CI 0.48–0.94) and disposal of child stool that is children whose stool was put/ rinsed in a latrine (APOR = 0.41; 95% CI: 0.23–0.74) as well as those that whose stool was thrown in garbage (APOR = 0.29; 95% CI: 0.12–0.72). Conclusion The prevalence of stunting among children aged 6–59 months in Kabale district was high. Practices/ factors independently associated with stunting among children aged 6–59 months included; age of the child, major source of food for the household and disposal of child stool. Addressing these factors requires a proper mix of both community and health based interventions. There is also need to strengthen on strategies for reducing stunting like; sanitation and hygiene as well as food and nutrition security within rural households.