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Background: The burden of advanced HIV disease remains a significant concern in sub-Saharan Africa. In 2015, the World Health Organization released recommendations to treat all people living with HIV (PLHIV) regardless of CD4 ("treat all") and in 2017 guidelines for managing advanced HIV disease. We assessed changes over time in the proportion of PLHIV with advanced HIV and their care cascade in two community settings in sub-Saharan Africa., Methods: Cross-sectional population-based surveys were conducted in Ndhiwa (Kenya) in 2012 and 2018 and in Eshowe (South Africa) in 2013 and 2018. We recruited individuals aged 15-59 years. Consenting participants were interviewed and tested for HIV at home. All participants with HIV had CD4 count measured. Advanced HIV was defined as CD4 < 200 cells/µL., Results: Overall, 6076 and 6001 individuals were included in 2012 and 2018 (Ndhiwa) and 5646 and 3270 individuals in 2013 and 2018 (Eshowe), respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 2012 (159/1376 (11.8%; 95% CI: 9.8-14.2)) to 2018 (53/1000 (5.0%; 3.8-6.6)). The proportion of individuals with advanced HIV on antiretroviral therapy (ART) was 9.1% (6.9-11.8) in 2012 and 4.2% (3.0-5.8) in 2018. In Eshowe, the proportion with advanced HIV was 130/1400 (9.8%; 8.0-11.9) in 2013 and 38/834 (4.5%; 3.3-6.1) in 2018. The proportion with advanced HIV among those on ART was 6.9% (5.5-8.8) in 2013 and 2.8% (1.8-4.3) in 2018. There was a significant increase in coverage for all steps of the care cascade among people with advanced HIV between the two Ndhiwa surveys, with all the changes occurring among men and not women. No significant changes were observed in Eshowe between the surveys overall and by sex., Conclusion: The proportion with advanced HIV disease decreased between the first and second surveys where all guidelines have been implemented between the two HIV surveys.

Background: Many countries are now replacing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) with a regimen containing tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Recognising laboratory limitations, Malawi opted to transition those on NNRTI-based first-line ART to TLD without viral load testing. We aimed to assess viral load and HIV drug resistance during 1 year following transition to TLD without previous viral load testing., Methods: In this prospective cohort study, we monitored 1892 adults transitioning from NNRTI-based first-line ART to the TLD regimen in the Médecins Sans Frontières-supported decentralised HIV programme in Chiradzulu District, Malawi. Eligible adults were enrolled between Jan 17 and May 11, 2019, at Ndunde and Milepa health centres, and between March 8 and May 11, 2019, at the Boma clinic. Viral load at the start of the TLD regimen was assessed retrospectively and measured at month 3, 6, and 12, and additionally at month 18 for those ever viraemic (viral load ≥50 copies per mL). Dolutegravir minimal plasma concentrations (C min ) were determined for individuals with viraemia. Drug-resistance testing was done at the start of TLD regimen and at viral failure (viral load ≥50 copies per mL, followed by viral load ≥500 copies per mL; resistance defined as Stanford score ≥15)., Findings: Of 1892 participants who transitioned to the TLD regimen, 101 (5·3%) were viraemic at TLD start. 89 of 101 had drug-resistance testing with 31 participants (34·8%) with Lys65Arg mutation, 48 (53·9%) with Met184Val/Ile, and 42 (40·4%) with lamivudine and tenofovir disoproxil fumerate dual resistance. At month 12 (in the per-protocol population), 1725 (97·9% [95% CI 97·1-98·5]) of 1762 had viral loads of less than 50 copies per mL, including 83 (88·3% [80·0-94·0]) of 94 of those who were viraemic at baseline. At month 18, 35 (97·2% [85·5-99·9]) of 36 who were viraemic at TLD start with lamivudine and tenofovir disoproxil fumarate resistance and 27 (81·8% [64·5-93·0]) of 33 of those viraemic at baseline without resistance had viral load suppression. 14 of 1838 with at least two viral load tests upon transitioning had viral failure (all with at least one dolutegravir C min value <640 ng/mL; active threshold), suggesting suboptimal adherence. High baseline viral load was associated with viral failure (adjusted odds ratio [aOR] 14·1 [2·3-87·4] for 1000 to <10 000 copies per mL; aOR 64·4 [19·3-215·4] for ≥10 000 copies per mL). Two people with viral failure had dolutegravir resistance at 6 months (Arg263Lys or Gly118Arg mutation), both were viraemic with lamivudine and tenofovir disoproxil fumarate resistance at baseline., Interpretation: High viral load suppression 1 year after introduction of the TLD regimen supports the unconditional transition strategy in Malawi. However, high pre-transition viral load, ongoing adherence challenges, and possibly existing nucleoside reverse transcriptase inhibitor resistance can lead to rapid development of dolutegravir resistance in a few individuals. This finding highlights the importance of viral load monitoring and dolutegravir-resistance surveillance after mass transitioning to the TLD regimen., Funding: Médecins Sans Frontières., Translations: For the French and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests DD reports honoraria for attending symposia, research grants, and support for attending meetings or travel from Gilead Sciences, MSD, Janssen-Cilag, and Merck Sharp and Dohme. A-GM reports funds for attending symposia, speaking, and research grants from ViiVHealthcare, Gilead Sciences, Theratechnologies, and Merck Sharp & Dohme. GP reports consulting fees from Gilead Sciences, ViiVHealthcare, Merck, Takeda, Pfizer, and TheraTechnologies; and honoraria from Gilead Sciences, ViiVHealthcare, and Merck. VC reports consulting fees and payment or honoraria from Gilead Sciences, ViiVHealthcare, and MSD; he is founder and member of the board of SkinDermic. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: In Western Kenya up to one-quarter of the adult population was human immunodeficiency virus (HIV)-infected in 2012. The Ministry of Health, Médecins Sans Frontières, and partners implemented an HIV program that surpassed the 90-90-90 UNAIDS targets. In this generalized epidemic, we compared the effectiveness of preexposure prophylaxis (PrEP) with improving continuum of care., Methods: We developed a dynamic microsimulation model to project HIV incidence and infections averted to 2030. We modeled 3 strategies compared to a 90-90-90 continuum of care base case: (1) scaling up the continuum of care to 95-95-95, (2) PrEP targeting young adults with 10% coverage, and (3) scaling up to 95-95-95 and PrEP combined., Results: In the base case, by 2030 HIV incidence was 0.37/100 person-years. Improving continuum levels to 95-95-95 averted 21.5% of infections, PrEP averted 8.0%, and combining 95-95-95 and PrEP averted 31.8%. Sensitivity analysis showed that PrEP coverage had to exceed 20% to avert as many infections as reaching 95-95-95., Conclusions: In a generalized HIV epidemic with continuum of care levels at 90-90-90, improving the continuum to 95-95-95 is more effective than providing PrEP. Continued improvement in the continuum of care will have the greatest impact on decreasing new HIV infections., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: HIV-positive individuals who maintain an undetectable viral load cannot transmit the virus to others. In 2012, an HIV population-based survey was conducted in Ndhiwa sub-county (Kenya) to provide information on the HIV local epidemic. We carried out a second survey 6 years after the first one, to assess progress in HIV diagnosis and care and differences in the HIV prevalence and incidence between the two surveys., Methods: A cross-sectional, population-based survey using cluster sampling and geospatial random selection was implemented in 2018, using the same design as 2012. Consenting participants aged 15-59 years were interviewed and tested for HIV at home. HIV-positive individuals received viral load testing (viral suppression defined as <1000 copies/ml) and Lag-Avidity EIA assay (to measure recent infection). The 90-90-90 UNAIDS indicators were also assessed., Results: Overall, 6029 individuals were included in 2018. HIV prevalence was 16.9%. Viral suppression among all HIV-positive was 88.3% in 2018 (vs. 39.9% in 2012, p < 0.001). HIV incidence was 0.75% in 2018 vs. 1.90% in 2012 (p = 0.07). In 2018, the 90-90-90 indicators were 93%-97%-95% (vs. 60%-68%-83% in 2012)., Conclusion: A two-fold increase in the HIV viral load suppression rate along with a decreasing trend in incidence was observed over 6 years in Ndhiwa sub-county. Achieving high rates of viral suppression in HIV populations that can lead to reducing HIV transmission in sub-Saharan contexts is feasible. Nevertheless, we will need further efforts to sustain this progress., (© 2021 Epicentre. Tropical Medicine & International Health published by John Wiley & Sons Ltd.)

Background: Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified., Setting: Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care)., Methods: Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL)., Results: Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens., Conclusions: Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor-based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We monitored a large-scale implementation of the Simple Amplification-Based Assay semi-quantitative viral load test for HIV-1 version I (SAMBA I Viral Load = SAMBA I VL) within Médecins Sans Frontières' HIV programmes in Malawi and Uganda, to assess its performance and operational feasibility., Methods: Descriptive analysis of routine programme data between August 2013 and December 2016. The dataset included samples collected for VL monitoring and tested using SAMBA I VL in five HIV clinics in Malawi (four peripheral health centres and one district hospital), and one HIV clinic in a regional referral hospital in Uganda. SAMBA I VL was used for VL testing in patients who had been receiving ART for between 6 months and ten years, to determine whether plasma VL was above or below 1000 copies/mL of HIV-1, reflecting ART failure or efficacy. Randomly selected samples were quantified with commercial VL assays. SAMBA I instruments and test performance, site throughput, and delays in communicating results to clinicians and patients were monitored., Results: Between August 2013 and December 2016 a total of 60 889 patient samples were analysed with SAMBA I VL. Overall, 0.23% of initial SAMBA I VL results were invalid; this was reduced to 0.04% after repeating the test once. Global test failure, including instrument failure, was 1.34%. Concordance with reference quantitative testing of VL was 2620/2727, 96.0% (1338/1382, 96.8% in Malawi; 1282/1345, 95.3% in Uganda). For Chiradzulu peripheral health centres and Arua Hospital HIV clinic, where testing was performed on-site, same-day results were communicated to clinicians for between 91% and 97% of samples. Same-day clinical review was obtained for 84.7% across the whole set of samples tested., Conclusions: SAMBA I VL testing is feasible for monitoring cohorts of 1000 to 5000 ART-experienced patients. Same-day results can be used to inform rapid clinical decision-making at rural and remote health facilities, potentially reducing time available for development of resistance and conceivably helping to reduce morbidity and mortality., (© 2020 John Wiley & Sons Ltd.)

Background: Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in medical wards and 6-month mortality according to LAM results., Methods: This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination, and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest x-ray, and CD4 count were systematically requested., Results: Among 387 inpatients, 54% had a CD4 <200 cells/µL, 64% had presumptive TB, and 90% had ≥1 TB symptom recorded in their medical file. LAM results were available for 99.0% of patients, microscopy for 62.8%, and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-month mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives ( P  = .013). In multivariable regression analyses, LAM-positive patients had a higher risk of mortality than LAM-negatives (adjusted odds ratio, 2.5; 95% CI, 1.1-5.8; P  = .037)., Conclusions: In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Patients with advanced HIV disease have a high risk of mortality, mainly from tuberculosis and cryptococcal meningitis. The advanced HIV disease management package recommended by WHO, which includes diagnostics, therapeutics, and patient psychosocial support, is barely implemented in many different countries. Here, we present a framework for the implementation of advanced HIV disease diagnostics. Laboratory and point-of-care-based reflex testing, coupled with provider-initiated requested testing, for cryptococcal antigen and urinary Mycobacterium tuberculosis lipoarabinomannan antigen, should be done for all patients with CD4 + cell counts of 200 cells per μL or less. Implementation of the advanced HIV disease package should be encouraged within primary health-care facilities and task shifting of testing to lay cadres could facilitate access to rapid results. Implementation of differentiated antiretroviral therapy delivery models can allow clinicians enough time to focus on the management of patients with advanced HIV disease. Efficient up-referral and post-discharge systems, including the development of patient-centric advanced HIV disease literacy, are also crucial. Implementation of the advanced HIV disease package is feasible at all health-care levels, and it should be part of the core of the global response towards ending AIDS as a public health threat., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Many adolescents living with HIV in sub-Saharan Africa struggle to achieve optimal adherence to antiretroviral therapy (ART), but few studies have investigated how their treatment-taking decisions are influenced by their social interactions with providers, caregivers and community leaders. This study aims to explore the narratives that define expectations of adherence to ART among adolescents living with HIV in a rural Malawian setting., Methods: Overall, 45 in-depth interviews were conducted in 2016 with adolescents living with HIV, caregivers, health workers and community leaders, and four group sessions using participatory tools were undertaken with adolescents. Interviews and group sessions were audio-recorded, transcribed and translated into English. Data were coded inductively and analysed thematically., Results: Adolescents were given strict behavioural codes around optimal treatment adherence, which were often enforced through encouragement, persuasian and threats. In HIV clinics, some staff supported adolescents with broader concerns relating to living with HIV, but other measures to address sub-optimal adherence in HIV clinics were perceived by patients as punitive, including pill-counts and increased frequency of clinic visits. Community leaders felt responsible for young peoples' health, sometimes attempting to influence their treatment-taking by threatening to withdraw services, or to publically "out" those deemed to be non-adherent. At home, discussions with adolescents about HIV were often limited to dose reminders, and some caretakers resorted to physical punishment to ensure adherence. While some adolescents complied with strictly-enforced adherence rules, others demonstrated resistance by hiding missed doses, secretly throwing away drugs, or openly refusing to take them., Conclusions: The potential of young people to adhere to their ART may be undermined by restrictive messages and punitive approaches to enforce and control their engagement with treatment at home, in the clinic and in the wider community. Interventions should focus on creating safe spaces for adolescents to speak frankly about the adherence challenges that they face and support for caregivers including home-based interventions., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Current eligibility criteria for urine lateral-flow lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count., Methods: We conducted a prospective, observational study that included all ambulatory, ≥15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy, and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive., Results: Of 485 patients included, 171 (35.3%) had a CD4 <200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (interquartile range: 129-546). LAM was positive in 24.9% patients with CD4 < 200 (50% LAM grades 2-4) and 12.5% with CD4 ≥ 200 (12.8% LAM grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM positivity was 56.7% (CD4 < 200) and 42.9% (CD4 ≥ 200), P = 0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM positive (ie, potentially missed patients). Overall, mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (grades 2-4: 36.0%; grade 1: 9.1%; negative: 7.4%; P < 0.001). LAM-positive patients with CD4 <200 cells/µL had higher risk of mortality than LAM negatives (adjusted hazard ratio: 3.2, 95% confidence interval: 1.4 to 7.2, P = 0.006), particularly those with LAM grades 2-4 (adjusted hazard ratio: 4.9, 95% confidence interval: 1.8 to 13.3, P = 0.002)., Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.

Introduction: Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi., Methods: We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure., Results and Discussion: Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed., Conclusions: Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB., Methods and Findings: We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results., Conclusions: LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients., Competing Interests: The authors have declared that no competing interests exist.

Background : Determine TB-LAM is a urine-based point-of-care assay for diagnosis of tuberculosis (TB). Objective : To assess the feasibility of using LAM to diagnose TB in adult HIV-positive patients in resource-limited settings. Methods : We performed a multi-centric mixed-methods cross-sectional descriptive study in the Democratic Republic of Congo, Malawi, and Mozambique. We used the study and program monitoring tools to estimate user workload, turn-around time (TAT), and proportion of patients with LAM and sputum-based results. We conducted semi-structured interviews to assess the user acceptability of the LAM. Results : The duration of the LAM testing activity per patient was 27 min (IQR 26-29); staff continued with other duties whilst waiting for the result. More patients had a LAM versus a sputum-based result: 168/213 (78.9%) vs 77/213 (36.1%), p < 0.001 in DRC; 691/695 (99.4%) vs 429/695 (61.7%), p < 0.001 in Malawi; and 646/647 (99.8%) vs 262/647 (40.5%), p < 0.001 in Mozambique. The median TAT in minutes when LAM was performed in the consultation room was 75 (IQR 45-188) in DRC, 29 (IQR 27-39) in Malawi, and 36 (IQR 35-41) in Mozambique. In comparison, the overall median TAT for sputum-based tests (smear or GeneXpert) was 2 (IQR 1-3) days. The median time to the first anti-TB drug dose for LAM-positive patients was 155 (IQR 90-504) minutes in DRC and 90 (IQR 60-117) minutes in Mozambique. The overall inter-reader agreement for the interpretation of the LAM result as positive or negative was 98.9%, kappa 0.97 (95%CI 0.96-0.99). Overall, LAM users found the test easy to perform. Major concerns were use of the reading card and the prior requirement of CD4 results before LAM testing. Conclusion : It is feasible to implement the LAM test in low resource settings. The short TAT permitted same day initiation of TB treatment for LAM-positive patients.

Background : Despite substantial progress in antiretroviral therapy (ART) scale up, some people living with HIV (PLHIV) continue to present with advanced HIV disease, contributing to ongoing HIV-related morbidity and mortality. Objective : We aimed to quantify population-level estimates of advanced HIV from three high HIV prevalence settings in Sub-Saharan Africa. Methods : Three cross-sectional surveys were conducted in (Ndhiwa (Kenya): September-November 2012), (Chiradzulu (Malawi): February-May 2013) and (Eshowe (South Africa): July-October 2013). Eligible individuals 15-59 years old who consented were interviewed at home followed by rapid HIV test and CD4 count test if tested HIV-positive. Advanced HIV was defined as CD4 < 200 cells/µl. We used logistic regression to identify patient characteristics associated with advanced HIV. Results : Among 18,991 (39.2% male) individuals, 4113 (21.7%) tested HIV-positive; 385/3957 (9.7% (95% Confidence Interval [CI]: 8.8-10.7)) had advanced HIV, ranging from 7.8% (95%CI 6.4-9.5) Chiradzulu (Malawi) to 11.8% (95%CI 9.8-14.2) Ndhiwa (Kenya). The proportion of PLHIV with advanced disease was higher among men 15.3% (95% CI 13.2-17.5) than women 7.5% (95%CI 6.6-8.6) p < 0.001. Overall, 62.7% of all individuals with advanced HIV were aware of their HIV status and 40.3% were currently on ART. Overall, 65.6% of individuals not on ART had not previously been diagnosed with HIV, while only 29.6% of those on ART had been on ART for ≥6 months. Individuals with advanced HIV disease were more likely to be men (adjusted Odds Ratio [aOR]; 2.1 (95%CI 1.7-2.6), and more likely not to be on ART (aOR; 1.7 (95%CI 1.3-2.1). Conclusion : In our study, about 1 in 10 PLHIV had advanced HIV with nearly 40% of them unaware of their HIV status. However, a substantial proportion of patients with advanced HIV were established on ART. Our findings suggest the need for a dual focus on alternative testing strategies to identify PLHIV earlier as well as improving ART retention.

Background: Latest WHO guidelines recommend starting HIV-positive individuals on antiretroviral therapy treatment (ART) regardless of CD4 count. We assessed additional impact of adopting new WHO guidelines., Methods: We used data of individuals aged 15-59 years from three HIV population surveys conducted in 2012 (Kenya) and 2013 (Malawi and South Africa). Individuals were interviewed at home followed by rapid HIV and CD4 testing if tested HIV-positive. HIV-positive individuals were classified as "eligible for ART" if (i) had ever been initiated on ART or (ii) were not yet on ART but met the criteria for starting ART based on country's guidelines at the time of the survey (Kenya-CD4< = 350 cells/μl and WHO Stage 3 or 4 disease, Malawi as for Kenya plus lifelong ART for all pregnant and breastfeeding women, South Africa as for Kenya plus ART for pregnant and breastfeeding women until cessation of breastfeeding)., Findings: Of 18,991 individuals who tested, 4,113 (21.7%) were HIV-positive. Using country's ART eligibility guidelines at the time of the survey, the proportion of HIV-infected individuals eligible for ART was 60.0% (95% CI: 57.2-62.7) (Kenya), 73.4% (70.8-75.8) (South Africa) and 80.1% (77.3-82.6) (Malawi). Applying WHO 2013 guidelines (eligibility at CD4< = 500 and Option B+ for pregnant and breastfeeding women), the proportions eligible were 82.0% (79.8-84.1) (Kenya), 83.7% (81.5-85.6) (South Africa) and 87.6% (85.0-89.8) (Malawi). Adopting "test and treat" would mean a further 18.0% HIV-positive individuals (Kenya), 16.3% (South Africa) and 12.4% (Malawi) would become eligible. In all countries, about 20% of adolescents (aged 15-19 years), became eligible for ART moving from WHO 2013 to "test and treat" while no differences by sex were observed., Conclusion: Countries that have already implemented 2013 WHO recommendations, the burden of implementing "test and treat" would be small. Youth friendly programmes to help adolescents access and adhere to treatment will be needed., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Longer intervals between clinic consultations for clinically stable antiretroviral therapy (ART) patients may improve retention in care and reduce facility workload. We assessed long-term retention among clinically stable ART patients attending six-monthly clinical consultations (SMCC) with three-monthly fast-track drug refills, and estimated the number of consultations "saved" by this model of ART delivery in rural Malawi., Methods: Stable patients (aged ≥18 years, on first-line ART ≥12 months, CD4 count ≥300 cells/mL 3 , without opportunistic infections, not pregnant/breastfeeding) were eligible for SMCC, with three-monthly drug refills from community health workers. Early enrollees were those starting SMCC within six months of eligibility, while late enrollees started at least 6 months after first eligibility. Kaplan-Meier methods were used to calculate cumulative probabilities of retention, stratified by timing of their enrolment and from first six-monthly clinical consultation. Cox regression was used to measure attrition hazards from the first six-monthly clinical consultation and risk factors for attrition, accounting for the time-varying nature of their eligibility and enrolment in this model of care., Results: From 2008 to 2015, 22,633 clinically stable patients from 11 facilities were eligible for SMCC for at least three months, contributing 74,264 person-years of observation, and 18,363 persons (81%) initiated this model of care. The median time from eligibility to enrolment was 12 months and the median cumulative time on SMCC was 14.5 months. Five years after first SMCC eligibility, cumulative probabilities of retention were 85.5% (95% CI: 84.0% to 86.9%) among early enrollees and 93% (95% CI: 92.8% to 94.0%) among late enrollees. The cumulative probability of retention from first SMCC was 97.0% (95% CI: 96.7% to 97.3%) and 86% (95% CI: 85% to 87%) at one and five years respectively. Among eligible patients initiating SMCC, the adjusted hazards of attrition were 2.4 (95% CI: 2.0 to 2.8) times higher during periods of SMCC discontinuation compared to periods on SMCC. Male sex, younger age, more recent SMCC eligibility and WHO Stage 3/4 conditions in the past year were also independently associated with attrition from SMCC. Approximately 26,000 consultations were "saved" during 2014., Conclusion: After five years, retention among patients attending SMCC was high, especially among women and older patients, and its scale-up could facilitate universal access to ART., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Human immunodeficiency virus (HIV) remains an important cause of hospitalization and death in low- and middle- income countries. Yet morbidity and in-hospital mortality patterns remain poorly characterized, with prior antiretroviral therapy (ART) exposure and treatment failure status largely unknown., Methods: We studied HIV-infected inpatients aged ≥13 years from cohorts in Kenya and the Democratic Republic of Congo (DRC), assessing clinical and demographic characteristics and hospitalization outcomes. Kenyan inpatients were prospectively enrolled during hospitalization; identical retrospective data were extracted for Congolese patients meeting the study criteria using routine medical information., Results: Among 338 HIV-infected patients in Kenya and 411 in DRC, 83.7% (95% confidence interval [CI], 79.4%-87.3%) and 97.3% (95% CI, 95.2%-98.5%), were admitted with advanced disease (defined as CD4 <200 cells/µL or World Health Organization stage 3/4 illness). Among inpatients with advanced HIV, 35.4% and 21.7% were ART-naive at admission. Patients under care had a median time of 44.1 (interquartile range [IQR], 18.4-90.5) months and 55.9 (IQR, 28.1-99.6) months on treatment; 17.2% (95% CI, 13.5%-21.6%) and 29.6% (95% CI, 25.4%-34.3%) died, 25.9% (95% CI, 16.0%-39.0%) and 22.5% (95% CI, 15.8%-31.0%) of these within 48 hours., Conclusions: Across 2 diverse clinical contexts in sub-Saharan Africa, advanced HIV inpatients were frequently admitted with low CD4 counts, often failing first-line ART. Earlier identification of treatment failure and rapid switching to second-line ART are needed.

Objectives: Data on cardiovascular disease risks among HIV-infected patients taking antiretroviral therapy (ART) over long periods of time are lacking in Sub-Saharan Africa., Methods: A cross-sectional study was conducted in Chiradzulu, Malawi from December 2015 to June 2016. HIV-infected persons on ART for more than 10 years (patients) and HIV-negative individuals (controls) from selected clinics participated. Following informed consent, a standardized questionnaire, clinical and laboratory examinations were performed. The prevalence of cardiovascular disease risk factors was calculated and stratified by age group., Results: Overall, 379 HIV-infected patients and 356 controls participated. Median time on ART among patients was 11.6 years (interquartile range 10.6-12.4).Within the 30-44, 45-59, and at least 60-year age groups, respectively, the prevalence of hypertension was 10.8, 20.4, and 44.7% among patients and 6.1, 25.8, and 42.9% among controls. Hypertension was previously undiagnosed in 60.3% patients and 37.0% controls with elevated blood pressure. The prevalence of diabetes within the respective age groups was 5.0, 6.4, and 13.2% among patients, and 3.4, 4.2, and 1.7% among controls. HIV-infected patients were more likely to have an glycated hemoglobin at least 6.0% (adjusted odds ratio 1.9; 95% confidence interval 1.1-3.2, P = 0.02). Prevalence of low-density lipoprotein cholesterol more than 130 mg/dl within the respective age groups was 8.0, 15.4, and 23.7% among patients and 1.8, 12.5, and 11.8% among controls., Conclusion: Noncommunicable diseases were a significant burden in Malawi, with high prevalence of hypercholesterolemia in all survey participants and an especially acute diabetes burden among older HIV infected. Hypertension screening and treatment services are needed among identified high-risk groups to cover unmet needs.

Objective: To assess mortality and clinical outcomes in children treated with antiretroviral therapy (ART) in four African vertical programmes between 2001 and 2010., Methods: Cohort analysis of data from HIV-infected children (<15 years old) initiating ART in four sub-Saharan HIV programmes in Kenya, Uganda and Malawi, between December 2001 and December 2010. Rates of mortality, programme attrition and first-line clinico-immunological failure were calculated by age group (<2, 2-4 and 5-14 years), 1 or 2 years after ART initiation, and risk factors were examined., Results: A total of 3949 children, 22.7% aged <2 years, 32.2% 2-4 years and 45.1% 5-14 years, were included. At ART initiation, 60.8% had clinical stage 3 or 4, and 46.5% severe immunosuppression. Overall mortality, attrition and 1-year failure rates were 5.1, 10.8 and 9.0 per 100 person-years, respectively. Immunosuppression, stage 3 or 4, and underweight were associated with increased rates of mortality, attrition and treatment failure. Adjusted estimates showed lower mortality hazard ratios (HR) among children aged 2-4 years (HR = 0.57, 95% CI 0.42-0.77 than children aged 5-14 years). One-year treatment failure incidence rate ratios (IRR) were similar regardless of age (IRR = 0.91, 95% CI 0.67-1.25 for <2 years; 1.01, 95% CI 0.83-1.23 for 2-4 years, vs. 5-14 years)., Conclusions: Good treatment outcomes were achieved during the first decade of HIV paediatric care despite the late start of therapy. Encouraging early HIV infant diagnosis in and outside prevention of mother-to-child transmission programmes, and linkage to care services for early ART initiation, is needed to reduce mortality and delay treatment failure., (© 2016 John Wiley & Sons Ltd.)

Background: The number of HIV-infected children starting antiretroviral treatment (ART) has increased in resource-limited settings during the past decades. However, there are still few published data on the characteristics of pediatric patients at program enrolment and on the dynamics of dropping out before the start of ART., Methods: We performed a retrospective cohort study among HIV-infected pediatric patients (age, 5-14 years) not yet started on ART enrolled in 4 HIV sub-Saharan African programs. Descriptive and risk factors for mortality and lost to follow-up (LFU) were investigated using adjusted parametric or Cox proportional hazard models., Results: A total of 2244 patients (52.8% girls) were enrolled in HIV care, a median of 2 days [interquartile range (IQR), 0-8 days] after HIV diagnosis. Baseline median CD4 cell count was 409 cells/μL (IQR, 203-478 cells/μL); 43% were in clinical stage 3 or 4, 71% required ART and 76.2% of these patients initiated therapy. Of those eligible not started on ART, 14% died and 59% were LFU. Median pre-ART follow-up was 4.4 months (IQR, 1.3-20 months) and was shorter for eligible patients. Mortality rates were 6.2 of 100 person-years [95% confidence interval (CI), 4.6-8.3] in the 0- to 6-month period and 1.3 of 100 person-years (95% CI, 0.9-2.0) in the 6- to 60-month period. LFU rates were 37.4 of 100 (95% CI, 33.0-42.4) and 8.3 of 100 person-years (95% CI, 7.1-9.8), respectively. Advanced HIV disease at presentation (low body mass index, stage 3 or 4, low CD4 count or tuberculosis diagnosis) was associated with increased mortality and LFU., Conclusions: Late presentation and delays in initiating ART among eligible children were responsible for the large incidence of patient losses during pre-ART follow-up in sub-Saharan Africa.

Introduction: The antiretroviral therapy (ART) programme supported by Médecins Sans Frontières in the rural Malawian district of Chiradzulu was one of the first in sub-Saharan Africa to scale up ART delivery in 2002. After more than a decade of continuous involvement, we conducted a population survey to evaluate the cascade of care, including population viral load, in the district., Methods: A cross-sectional household-based survey was conducted between February and May 2013. Using a multistage cluster sampling method, we recruited all individuals aged 15 to 59 years living in 4125 randomly selected households. Each consenting individual was interviewed and tested for HIV at home. All participants who tested positive had their CD4 count and viral load measured. The LAg-Avidity assay was used to distinguish recent from long-term infections. Viral suppression was defined as a viral load below 1000 copies/mL., Results: Of 8271 individuals eligible for the study, 7269 agreed to participate and were tested for HIV (94.1% inclusion for women and 80.3% for men). Overall HIV prevalence and incidence were 17.0% (95% CI 16.1 to 17.9) and 0.39 new cases per 100 person-years (95% CI 0.0 to 0.77), respectively. Coverage at the other steps along the HIV care cascade was as follows: 76.7% (95% CI 74.4 to 79.1) had been previously diagnosed, 71.2% (95% CI 68.6 to 73.6) were under care and 65.8% (95% CI 62.8 to 68.2) were receiving ART. Finally, the proportion of participants who were HIV positive with a viral load ≤ 1000 copies/mL reached 61.8% (95% CI 59.0 to 64.5)., Conclusions: This study demonstrates that a high level of population viral suppression and low incidence can be achieved in high HIV prevalence and resource-limited settings.

Introduction: Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation - especially HIV incidence, population viral load, and ART eligibility - is rare in sub-Saharan Africa., Design/methods: To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 15-59 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4 cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections., Results: Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.0-25.2] and 1.9 new cases/100 person-years (95% CI 1.1-2.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.8-61.9) were previously diagnosed, 53.1% (95% CI 50.5-55.7) were receiving care, and 39.7% (95% CI 37.1-42.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3-62.7) to 82.0% (95% CI 79.5-84.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4 cell count (500-749 vs. ≥750 cells/μl, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.20-0.60, P < 0.01)., Conclusion: This study demonstrates how population-level data can help optimize HIV programs. Based on these results, new regional programs are prioritizing diagnosis and expanding ART eligibility, key steps to reach undetectable viral load.

Background: Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management., Methods: Analysis of individual electronic health records from 4 HIV programs in Malawi, Kenya, Uganda, and Cambodia, linked to data from 5 cross-sectional virological studies conducted among patients receiving first-line antiretroviral therapy (ART) for ≥6 months. Adjusted logistic and Cox-regression models were used to identify risk factors for drug resistance and subsequent mortality., Results: A total of 2257 patients (62% women) were included. At ART initiation, median CD4 cell count was 100 cells per microliter (interquartile range, 40-165). A median of 25.1 months after therapy start, 18% of patients had ≥400 and 12.4% ≥1000 HIV RNA copies per milliliter. Of 180 patients with drug resistance data, 83.9% had major resistance(s) to nucleoside or nonnucleoside reverse transcriptase inhibitors, and 74.4% dual resistance. Resistance to nevirapine, lamivudine, and efavirenz was common, and 6% had etravirine cross-resistance. Risk factors for resistance were young age (<35 years), low CD4 cell count (<200 cells/μL), and poor treatment adherence. During 4978 person-years of follow-up after virological testing (median = 31.8 months), 57 deaths occurred [rate = 1.14/100 person-years; 95% confidence interval (CI): 0.88 to 1.48]. Mortality was higher in patients with resistance (hazard ratio = 2.08; 95% CI: 1.07 to 4.07 vs. <400 copies/mL), and older age (hazard ratio = 2.41; 95% CI: 1.24 to 4.71 for ≥43 vs. ≤34 years), and lower in those receiving ART for >30 months., Conclusions: Our findings underline the importance of optimal treatment adherence and adequate virological response monitoring and emphasize the need for resistance surveillance initiatives even in HIV programs achieving high virological suppression rates.

Routine viral-load (VL) testing of HIV-infected individuals on antiretroviral therapy (ART) is used to monitor treatment efficacy. However, due to logistical challenges, implementation of VL has been difficult in resource-limited settings. The aim of this study was to evaluate the performance of the SAMBA semi-Q (simple amplification-based assay semiquantitative test for HIV-1) in London, Malawi, and Uganda. The SAMBA semi-Q can distinguish between patients with VLs above and below 1,000 copies/ml. The SAMBA semi-Q was validated with diluted clinical samples and blinded plasma samples collected from HIV-1-positive individuals. SAMBA semi-Q results were compared with results from the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test, v2.0. Testing of 96 2- to 10-fold dilutions of four samples containing HIV-1 subtype C as well as 488 samples from patients in the United Kingdom, Malawi, and Uganda yielded an overall accuracy for the SAMBA semi-Q of 99% (95% confidence interval [CI], 93.8 to 99.9%) and 96.9% (95% CI 94.9 to 98.3%), respectively, compared to to the Roche test. Analysis of VL data from patients in Malawi and Uganda showed that the SAMBA cutoff of 1,000 copies/ml appropriately distinguished treated from untreated individuals. Furthermore, analysis of the viral loads of 232 patients on ART in Malawi and Uganda revealed similar patterns for virological control, defined as either <1,000 copies/ml (SAMBA cutoff) or <5,000 copies/ml (WHO 2010 criterion; WHO, Antiretroviral Therapy for HIV Infection in Adults and Adolescents: Recommendations for a Public Health Approach, 2010). This study suggests that the SAMBA semi-Q has adequate concurrency with the gold standard measurements for viral load. This test can allow VL monitoring of patients on ART at the point of care in resource-limited settings., (Copyright © 2014 Ritchie et al.)

Objectives: Further scale-up of antiretroviral therapy (ART) to those in need while supporting the growing patient cohort on ART requires continuous adaptation of healthcare delivery models. We describe several approaches to manage stable patients on ART developed by Médecins Sans Frontières together with Ministries of Health in four countries in sub-Saharan Africa., Methods: Using routine programme data, four approaches to simplify ART delivery for stable patients on ART were assessed from a patient and health system perspective: appointment spacing for clinical and drug refill visits in Malawi, peer educator-led ART refill groups in South Africa, community ART distribution points in DRC and patient-led community ART groups in Mozambique., Results: All four approaches lightened the burden for both patients (reduced travel and lost income) and health system (reduced clinic attendance). Retention in care is high: 94% at 36 months in Malawi, 89% at 12 months in DRC, 97% at 40 months in South Africa and 92% at 48 months in Mozambique. Where evaluable, service provider costs are reported to be lower., Conclusion: Separating ART delivery from clinical assessments was found to benefit patients and programmes in a range of settings. The success of community ART models depends on sufficient and reliable support and resources, including a flexible and reliable drug supply, access to quality clinical management, a reliable monitoring system and a supported lay workers cadre. Such models require ongoing evaluation and further adaptation to be able to reach out to more patients, including specific groups who may be challenged to meet the demands of frequent clinic visits and the integrated delivery of other essential chronic disease interventions., (© 2014 John Wiley & Sons Ltd.)

Background: Gaining understanding of the period before antiretroviral therapy (ART) is needed to improve treatment outcomes and to reduce HIV transmission. This study describes the cascade of enrollment in HIV care, pre-ART follow-up, and predictors of mortality and lost to follow-up (LTFU) before ART initiation., Methods: We conducted a cohort study among HIV-infected adult patients not yet started on ART in 4 HIV Sub-Saharan African programs. Patient follow-up began at enrollment and ended at the earliest of death, transfer-out, ART initiation, last visit date, or 60 months postenrollment. Risk factors for death and LTFU were investigated during the periods 0-6 and 6-60 months., Results: A total of 55,789 patients (65.4% women) were included as follows: 44.2% in clinical stage 3 or 4, with median CD4 of 261 cells per microliter [interquartile range (IQR): 125-447]. Patient care started with a median of 3 days (IQR: 0-11) after HIV diagnosis, and 31,104 of 55,789 (55.8%) patients had CD4 counts performed within 1 month of enrollment. Of 47,283 patients with known ART eligibility status at enrollment, 36,969 (78.2%) patients required ART and 27,798 of 36,969 (75.7%) patients initiated therapy. Median follow-up was 2.5 months (IQR: 0.9-13.1). Mortality and LTFU rates were 3.9 per 100 person-years [95% confidence interval (CI): 3.7 to 4.1] and 28.3 per 100 person-years (95% CI: 27.8 to 28.8), respectively. Regardless of period, increased mortality and LTFU were associated with male, lower body mass index, advanced clinical stage, and lower CD4 cell count., Conclusions: Short delays between HIV testing and care enrollment were observed in our HIV programs, but delays to determine ART eligibility were long. Interventions to initiate ART earlier, specifically targeted to men, are needed to improve patient retention in Africa.

Background: Expanding access to antiretroviral therapy (ART) in sub-Saharan Africa requires implementation of alternative care delivery models to traditional physician-centered approaches. This longitudinal analysis compares outcomes of patients initiated on antiretroviral therapy (ART) by non-physician and physician providers., Methods: Adults (≥15 years) initiating ART between September 2007 and March 2010, and with >1 follow-up visit were included and classified according to the proportion of clinical visits performed by nurses or by clinical officers (≥ 80% of visits). Multivariable Poisson models were used to compare 2-year program attrition (mortality and lost to follow-up) and mortality by type of provider. In sensitivity analyses only patients with less severe disease were included., Results: A total of 10,112 patients contributed 14,012 person-years to the analysis: 3386 (33.5%) in the clinical officer group, 1901 (18.8%) in the nurse care group and 4825 (47.7%) in the mixed care group. Overall 2-year program retention was 81.8%. Attrition was lower in the mixed care and higher in the clinical officer group, compared to the nurse group (adjusted incidence rate ratio [aIRR]=0.54, 95%CI 0.45-0.65; and aIRR=3.03, 95%CI 2.56-3.59, respectively). While patients initiated on ART by clinical officers in the mixed care group had lower attrition (aIRR=0.36, 95%CI 0.29-0.44) than those in the overall nurse care group; no differences in attrition were found between patients initiated on ART by nurses in the mixed care group and those included in the nurse group (aIRR=1.18, 95%CI 0.95-1.47). Two-year mortality estimates were aIRR=0.72, 95%CI 0.49-1.09 and aIRR=5.04, 95%CI 3.56-7.15, respectively. Slightly higher estimates were observed when analyses were restricted to patients with less severe disease., Conclusion: The findings of this study support the use of a mixed care model with well trained and regularly supervised nurses and medical assistants to provide HIV care in countries with high HIV prevalence.

Objectives: To examine age differences in mortality and programme attrition amongst paediatric patients treated in four African HIV programmes., Methods: Longitudinal analysis of data from patients enrolled in HIV care. Two-year mortality and programme attrition rates per 1000 person-years stratified by age group (<2, 2-4 and 5-15 years) were calculated. Associations between outcomes and age and other individual-level factors were studied using multiple Cox proportional hazards (mortality) and Poisson (attrition) regression models., Results: Six thousand two hundred and sixty-one patients contributed 9500 person-years; 27.1% were aged <2 years, 30.1% were 2-4, and 42.8% were 5-14 years old. At programme entry, 45.3% were underweight and 12.6% were in clinical stage 4. The highest mortality and attrition rates (98.85 and 244.00 per 1000 person-years), and relative ratios (adjusted hazard ratio [aHR] = 1.92, 95% CI 1.56-2.37; incidence ratio [aIR] = 2.10, 95% CI 1.86-2.37, respectively, compared with the 5- to 14-year group) were observed amongst the youngest children. Increased mortality and attrition were also associated with advanced clinical stage, underweight and diagnosis of tuberculosis at programme entry., Conclusions: These results highlight the need to increase access, diagnose and provide early HIV care and to accelerate antiretroviral treatment initiation for those eligible. Adapted education and support for children and their families would also be important., (© 2013 John Wiley & Sons Ltd.)

Objectives: To identify factors influencing mortality in an HIV programme providing care to large numbers of injecting drug users (IDUs) and patients co-infected with hepatitis C (HCV)., Methods: A longitudinal analysis of monitoring data from HIV-infected adults who started antiretroviral therapy (ART) between 2003 and 2009 was performed. Mortality and programme attrition rates within 2 years of ART initiation were estimated. Associations with individual-level factors were assessed with multivariable Cox and piece-wise Cox regression., Results: A total of 1671 person-years of follow-up from 1014 individuals was analysed. Thirty-four percent of patients were women and 33% were current or ex-IDUs. 36.2% of patients (90.8% of IDUs) were co-infected with HCV. Two-year all-cause mortality rate was 5.4 per 100 person-years (95% CI, 4.4-6.7). Most HIV-related deaths occurred within 6 months of ART start (36, 67.9%), but only 5 (25.0%) non-HIV-related deaths were recorded during this period. Mortality was higher in older patients (HR = 2.50; 95% CI, 1.42-4.40 for ≥40 compared to 15-29 years), and in those with initial BMI < 18.5 kg/m(2) (HR = 3.38; 95% CI, 1.82-5.32), poor adherence to treatment (HR = 5.13; 95% CI, 2.47-10.65 during the second year of therapy), or low initial CD4 cell count (HR = 4.55; 95% CI, 1.54-13.41 for <100 compared to ≥100 cells/μl). Risk of death was not associated with IDU status (P = 0.38)., Conclusion: Increased mortality was associated with late presentation of patients. In this programme, death rates were similar regardless of injection drug exposure, supporting the notion that satisfactory treatment outcomes can be achieved when comprehensive care is provided to these patients., (© 2012 Blackwell Publishing Ltd.)

Objective: We investigated the association between immune response and mortality in four HIV African programs supported by Médecins Sans Frontières., Design: Multicentric retrospective cohort study., Methods: All antiretroviral therapy (ART) naive adults (>15 years) who initiated therapy between March 2001 and November 2010 and receiving therapy for 9 months or more were included. We described the evolution of mortality over time. Mixed Poisson models were used to assess the effect of updated CD4 cell counts and other potential risk factors on mortality., Findings: A total of 24 037 patients, of which 68% were women, contributed 69 516.2 person-years of follow-up. At ART initiation, 5718 patients (23.7%) were classified as WHO clinical stage 4, 1587 (6.6%) had a BMI below 16 kg/m and 2568 (10.7%) had CD4 cell count below 50 cells/μl. A total of 568 (2.4%) deaths were recorded during the study period. In the CD4 response categories 500 cells/μl or more, 350-499, 200-349, 50-199 cells/μl and less than 50 cells/μl, unadjusted mortality rates were 0.36; 0.58; 0.88; 1.91 and 7.43 per 100 person-years, respectively. In multivariate analysis, higher mortality was observed in patients with CD4 response levels 350-499 cells/μl [adjusted hazard ratio (aHR) 1.70, 95% confidence interval (CI) 1.26-2.30] and for those between 200-349 (aHR 2.56; 95% CI 1.93-3.38), compared to those with 500 cells/μl or more., Interpretation: The observed higher survival of patients with a CD4 response to ART higher than 500 cells/μl supports the need of further research to evaluate the individual benefit of initiating ART at higher CD4 levels in sub-Saharan Africa.

Background: Ensuring long-term adherence to therapy is essential for the success of HIV treatment. As access to viral load monitoring and genotyping is poor in resource-limited settings, a simple tool to monitor adherence is needed. We assessed the relationship between an indicator based on timeliness of clinic attendance and virological response and HIV drug resistance., Methods: Data from 7 virological cross-sectional studies were pooled. An adherence indicator was calculated as the number of appointments attended with delay divided by the number of months between antiretroviral treatment (ART) initiation and date of virological testing and multiplying this by 100. Delays of 1 or more to 5 or more days were considered in turn. Multivariate random-intercept logistic regression was fitted to examine the effect on outcomes, separately for adults and children., Results: A total of 3580 adults and 253 children were included. Adults were followed for a median of 26.0 months (IQR 12.8-45.0) and attended a median of 24 visits (IQR 13-34). The 1-day delay adherence indicator was strongly associated with viral load suppression (OR 0.96, 95% CI 0.95-0.97 per unit increase), virological failure (OR 1.05, 95% CI 1.03-1.06) and HIV drug resistance (OR 1.03, 95% CI 1.01-1.05) after adjusting for initial age and CD4 count, previous ART experience, type of regimen and Tuberculosis diagnosis at start of therapy. Similar results were observed in children., Conclusion: An adherence indicator based on timeliness of clinic attendance predicts strongly both virological response and drug resistance, and could help to timely identify non-adherent patients in settings where viral load monitoring is not available.

Objective: The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses., Methods: We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis., Results: Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76-1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61-2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17-1.66 vs. 1.29 to 1.34)., Conclusions: In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.

Objective: To describe patient antiretroviral therapy (cART) outcomes associated with intensive decentralization of services in a rural HIV program in Malawi., Methods: Longitudinal analysis of data from HIV-infected patients starting cART between August 2001 and December 2008 and of a cross-sectional immunovirological assessment conducted 12 (±2) months after therapy start. One-year mortality, lost to follow-up, and attrition (deaths and lost to follow-up) rates were estimated with exact Poisson 95% confidence intervals (CI) by type of care delivery and year of initiation. Association of virological suppression (<50 copies/mL) and immunological success (CD4 gain ≥100 cells/µL), with type of care was investigated using multiple logistic regression., Results: During the study period, 4322 cART patients received centralized care and 11,090 decentralized care. At therapy start, patients treated in decentralized health facilities had higher median CD4 count levels (167 vs. 130 cell/µL, P<0.0001) than other patients. Two years after cART start, program attrition was lower in decentralized than centralized facilities (9.9 per 100 person-years, 95% CI: 9.5-10.4 vs. 20.8 per 100 person-years, 95% CI: 19.7-22.0). One year after treatment start, differences in immunological success (adjusted OR=1.23, 95% CI: 0.83-1.83), and viral suppression (adjusted OR=0.80, 95% CI: 0.56-1.14) between patients followed at centralized and decentralized facilities were not statistically significant., Conclusions: In rural Malawi, 1- and 2-year program attrition was lower in decentralized than in centralized health facilities and no statistically significant differences in one-year immunovirological outcomes were observed between the two health care levels. Longer follow-up is needed to confirm these results.

Objective: Viral load testing is used in the HIV programme of Chiradzulu, Malawi, to confirm the diagnosis of immunological failure to prevent unnecessary switching to second-line therapy. Our objective was to quantify the benefit of this strategy for management of treatment failure in a large decentralized HIV programme in Africa., Methods: Retrospective analysis of monitoring data from adults treated with first-line antiretroviral regimens for >1 year and meeting the WHO immunological failure criteria in an HIV programme in rural Malawi. The positive predictive value of using immunological failure criteria to diagnose virological failure (viral load >5000 copies/ml) was estimated., Results: Of the 227 patients with immunological failure (185 confirmed with a repeat CD4 measurement), 155 (68.2%) had confirmatory viral load testing. Forty-four (28.4%) had viral load >5000 copies/ml and 57 (36.8%) >1000 copies/ml. Positive predictive value was 28.4% (95% CI 21.4-36.2%). Repeat CD4 count testing showed that 41% of patients initially diagnosed with immunological failure did no longer meet failure criteria., Conclusions: Our results support the need for confirming all cases of immunological failure with viral load testing before switching to second-line ART to optimize the use of resources in developing countries., (© 2011 Blackwell Publishing Ltd.)