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Point-of-care urine-lipoarabinomannan (LAM) Alere Determine TB-LAM assay has shown utility diagnosing tuberculosis (TB) in HIV-positive, severely immunocompromised, TB-symptomatic patients. We assessed LAM results in severely immunocompromised patients, who had LAM systematically performed at new or follow-up HIV consultations. This was a prospective, observational study on consecutive ambulatory, > 15-year-old HIV-positive patients with CD4 < 100 cells/µL in Mozambique. Clinical assessments and LAM were performed for all and microscopy, Xpert, sputum culture, and chest X-ray for LAM-positive participants. Patients were followed up for 6 months. Of 360 patients, half were ART-naive. Lipoarabinomannan positivity was 11.9% (43/360), higher among symptomatic patients compared with asymptomatic: 18.5% (30/162), and 6.6% (13/198), respectively, P = 0.001. Tuberculosis was bacteriologically confirmed in 6/35 LAM-positive patients (2 of them asymptomatic). Lipoarabinomannan positivity was associated with higher risk of mortality (adjusted odds ratio [aOR]: 4.6, 95% CI: 1.3–15.6, P = 0.015). Systematic urine-LAM allows for rapid TB treatment initiation in severely immunocompromised HIV ambulatory patients and identifies patients at a higher risk of death.

ObjectivesThis pre–post implementation study evaluated the introduction of fixed dose combination (FDC) medications for atherosclerotic cardiovascular disease (ASCVD) secondary prevention into routine care in a humanitarian setting.SettingTwo Médecins sans Frontières (MSF) primary care clinics serving Syrian refugee and host populations in north Lebanon.ParticipantsConsenting patients ≥18 years with existing ASCVD requiring secondary prevention medication were eligible for study enrolment. Those with FDC contraindication(s) or planning to move were excluded. Of 521 enrolled patients, 460 (88.3%) were retained at 6 months, and 418 (80.2%) switched to FDC. Of these, 84% remained on FDC (n=351), 8.1% (n=34) discontinued and 7.9% (n=33) were lost to follow-up by month 12.InterventionsEligible patients, enrolled February–May 2019, were switched to Trinomia FDC (atorvastatin 20 mg, aspirin 100 mg, ramipril 2.5/5/10 mg) after 6 months’ usual care. During the study, the COVID-19 pandemic, an economic crisis and clinic closures occurred.Outcome measuresDescriptive and regression analyses compared key outcomes at 6 and 12 months: medication adherence, non-high density lipoprotein cholesterol (non-HDL-C) and systolic blood pressure (SBP) control. We performed per-protocol, intention-to-treat and secondary analyses of non-switchers.ResultsAmong 385 switchers remaining at 12 months, total adherence improved 23%, from 63% (95% CI 58 to 68) at month 6, to 86% (95% CI 82 to 90) at month 12; mean non-HDL-C levels dropped 0.28 mmol/L (95% CI −0.38 to −0.18; pConclusionImplementing an ASCVD secondary prevention FDC improved adherence and CVD risk factors in MSF clinics in Lebanon, with potential for wider implementation by humanitarian actors and host health systems.

To pilot an intervention on the prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in an antenatal care and maternity unit in Maputo, Mozambique, during 2017-2019.We included HBV in the existing screening programme (for human immunodeficiency virus (HIV) and syphilis) for pregnant women at their first consultation, and followed mother-child dyads until 9 months after delivery. We referred women who tested positive for hepatitis B surface antigen (HBsAg) for further tests, including hepatitis B e antigen (HBeAg) and HBV viral load. According to the results, we proposed tenofovir for their own health or for PMTCT. We administered birth-dose HBV vaccine and assessed infant HBV status at 9 months.Of 6775 screened women, 270 (4.0%) were HBsAg positive; in those for whom data were available, 24/265 (9.1%) were HBeAg positive and 14/267 (5.2%) had a viral load of 200 000 IU/mL. Ninety-eight (36.3%) HBsAg-positive women were HIV coinfected, 97 of whom were receiving antiretroviral treatment with tenofovir. Among HIV-negative women, four had an indication for tenofovir treatment and four for tenofovir PMTCT. Of 217 exposed liveborn babies, 181 (83.4%) received birth-dose HBV vaccine, 160 (88.4%) of these 24 hours after birth. At the 9-month follow-up, only one out of the 134 tested infants was HBV positive.Our nurse-led intervention highlights the feasibility of integrating PMTCT of HBV into existing antenatal care departments, essential for the implementation of the triple elimination initiative. Universal birth-dose vaccination is key to achieving HBV elimination.Piloter une action de prévention d'une transmission de la mère à l'enfant (PTME) du virus de l'hépatite B (VHB) dans une maternité et unité de soins prénataux à Maputo, au Mozambique, entre 2017 et 2019.Nous avons inclus le VHB dans le programme existant visant à dépister le virus de l'immunodéficience humaine (VIH) et la syphilis chez les femmes enceintes lors de leur première consultation. Nous avons également suivi les dyades mère-enfant jusqu'à 9 mois après l'accouchement. Nous avons orienté les femmes positives à la présence de l'antigène de surface (HBsAg) de l'hépatite B vers d'autres tests, dont ceux détectant l'antigène e (HBeAg) et la charge virale du VHB. En fonction des résultats, nous avons proposé un traitement au ténofovir pour leur propre santé ou pour la PTME. Enfin, nous avons administré un vaccin contre le VHB à la naissance et évalué le statut sérologique du nourrisson à neuf mois.Sur 6775 femmes dépistées, 270 (4,0%) étaient positives au HBsAg; parmi celles pour qui des données étaient disponibles, 24/265 (9,1%) étaient positives au HBeAg et 14/267 (5,2%) présentaient une charge virale supérieure à 200 000 UI/ml. Le VIH a en outre été détecté chez 98 (36,3%) femmes positives au HBsAg, 97 d'entre elles faisant l'objet d'un traitement antirétroviral au ténofovir. Parmi les femmes négatives au VIH, quatre avaient reçu des indications de traitement au ténofovir et quatre s'étaient vu conseiller le ténofovir dans le cadre d'une PTME. Sur les 217 bébés exposés, 181 (83,4%) ont été vaccinés contre le VHB à la naissance, 160 (88,4%) d'entre eux moins de 24 heures après leur venue au monde. Lors de la visite de suivi neuf mois après la naissance, seul un des 134 nourrissons testés était positif au VHB.Notre action dirigée par le personnel infirmier démontre qu'il est possible d'intégrer la PTME du VHB dans les départements de soins prénataux existants, une démarche essentielle à la mise en œuvre de l'initiative de triple élimination. La vaccination universelle à la naissance est cruciale pour éradiquer le VHB.Realizar una intervención piloto sobre la prevención de la transmisión maternofilial (PTMF) del virus de la hepatitis B (VHB) en una unidad de asistencia prenatal y maternidad en Maputo, Mozambique, entre 2017 y 2019.Se incluyó el VHB en el programa existente de cribado del virus de la inmunodeficiencia humana (VIH) y de la sífilis para las embarazadas en su primera consulta, y se realizó un seguimiento de las parejas maternofiliales hasta nueve meses después del parto. Se derivó a las mujeres que dieron positivo en la prueba del antígeno de superficie del virus de la hepatitis B (AgHBs) para que se sometieran a otras pruebas, como el antígeno De las 6775 mujeres analizadas, 270 (4,0 %) dieron positivo en la prueba del AgHBs; entre las que disponían de datos, 24/265 (9,1 %) eran positivas en la prueba del AgHBe y 14/267 (5,2 %) tenían una concentración vírica superior a 200 000 UI/ml. Noventa y ocho (36,3 %) mujeres con AgHBs positivo estaban coinfectadas por el VIH, 97 de las que recibían tratamiento antirretrovírico con tenofovir. Entre las mujeres con VIH negativo, cuatro tenían indicación de tratamiento con tenofovir y cuatro con tenofovir para la PTMF. De los 217 bebés nacidos vivos expuestos, 181 (83,4 %) recibieron la vacuna contra el VHB al nacer, 160 (88,4 %) de ellos en las primeras 24 horas de vida. En la visita de seguimiento a los nueve meses, solo uno de los 134 lactantes analizados dio positivo en la prueba del VHB.Esta intervención dirigida por enfermeras demuestra la viabilidad de integrar la PTMF del VHB en los departamentos de asistencia prenatal existentes, lo que es esencial para la aplicación de la iniciativa de triple eliminación. La vacunación universal al nacer es fundamental para lograr la erradicación del VHB.الغرض تجربة تدخل للوقاية من انتقال فيروس التهاب الكبد ب (HBV) من الأم إلى الطفل (PMTCT) في وحدة رعاية ما قبل الولادة والأمومة في مابوتو، موزامبيق، خلال الفترة من 2017 إلى 2019. الطريقة قمنا بتضمين فيروس التهاب الكبد ب في برنامج الفحص الحالي (لفيروس نقص المناعة البشرية (HIV) والزهري) للنساء الحوامل في زيارة الاستشارة الأولى، وتابعنا ثنائيات الأم والطفل حتى 9 أشهر بعد الولادة. قمنا بإحالة النساء اللاتي ثبتت إصابتهن بمستضد التهاب الكبد ب السطحي (HBsAg) بهدف إجراء المزيد من الاختبارات، بما في ذلك مستضد التهاب الكبد ب هـ (HBeAg) والحمل الفيروسي بفيروس التهاب الكبد ب. وفقًا للنتائج، اقترحنا عقار Tenofovir (تينوفوفير) لصحتهم أو لمنع انتقال الفيروس من الأم إلى الطفل. قمنا بإعطاء جرعة الولادة من لقاح فيروس التهاب الكبد ب، وقمنا بتقييم حالة الإصابة بفيروس التهاب الكبد ب في سن 9 أشهر. النتائج من بين 6775 امرأة تم فحصها، كانت 270 (4.0%) نتيجتهن إيجابية للإصابة بمستضد التهاب الكبد السطحي (HBsAg)؛ في أولئك اللاتي كانت البيانات متاحة لهن، وكانت 24/265 (9.1%) إيجابية للإصابة بمستضد التهاب الكبد ب هـ، و14/267 (5.2%) كان لديهن حمل فيروسي200000 وحدة دولية/مل. ثمانية وتسعون (36.3%) من النساء ذوات النتيجة الإيجابية للإصابة بمستضد التهاب الكبد السطحي، كن مصابات جميعهن بفيروس نقص المناعة البشرية، بينما 97 منهن كن يتلقين العلاج المضاد للفيروسات القهقرية مع تينوفوفير. من بين النساء ذوات النتائج السلبية للإصابة بفيروس نقص المناعة البشرية، كان لدى أربع منهن دواع للعلاج بعقار تينوفوفير، وأربع لعقار تينوفوفير للوقاية من انتقال الفيروس من الأم إلى الطفل. من بين 217 طفلًا مولودًا على قيد الحياة، تلقى 181 (83.4%) جرعة الولادة من لقاح التهاب الكبد ب، و160 (88.4%) منها كانت قبل 24 ساعة بعد الولادة. في المتابعة التي استمرت على مدى 9 أشهر، كان واحد فقط من أصل 134 رضيعًا، مصابًا بفيروس التهاب الكبد ب. الاستنتاج إن التدخل الخاص بنا، والذي يتم بقيادة الممرضة، يسلط الضوء على جدوى دمج منع انتقال فيروس التهاب الكبد ب من الأم إلى الطفل، في أقسام الرعاية السابقة للولادة، وهو أمر ضروري لتنفيذ مبادرة الإقصاء الثلاثي. يعتبر التطعيم الشامل عند الولادة أمرًا أساسيًا لتحقيق القضاء على فيروس التهاب الكبد ب.目的 旨在于 2017–2019 年在莫桑比克马普托试点运行一项在产前保健和产科服务时预防乙型肝炎病毒 (HBV) 母婴传播 (PMTCT) 的干预措施。方法 我们在孕妇第一次询诊时将 HBV 纳入当前的筛查计划【包括人体免疫缺损病毒 (HIV) 和梅毒】中,并在婴儿出生 9 个月后追踪产妇和婴儿的情况。我们将乙肝表面抗原 (HBsAg) 检测阳性的孕妇转诊接受进一步的检查,包括乙型肝炎病毒 e 抗原 (HBeAg) 和 HBV 病毒载量。根据检查结果,我们会建议服用替诺福韦,这既是出于孕妇自身的健康考虑,也是出于预防母婴传播 (PMTCT) 考虑。我们给新生儿注射出生剂量的 HBV 疫苗,并评估他们在 9 个月时的 HBV 状态。结果在筛查的 6775 名女性中,270 (4.0%) 呈 HBsAg 阳性;在拥有可用数据的女性中,24/265 (9.1%) 呈 HBeAg 阳性,且 14/267 (5.2%) 的病毒载量200 000 IU/mL。98 (36.3%) 位 HBsAg 阳性女性同时感染 HIV,其中 97 位女性正在服用替诺福韦进行抗逆转录病毒治疗。在 HIV 阴性的女性中,4 人具有替诺福韦治疗指征,4 人具有替诺福韦母婴传播预防指征。在 217 位出生时暴露的婴儿中,181 (83.4%) 人接种了出生剂量的 HBV 疫苗,其中 160 (88.4%) 人是在出生后 24 小时内接种的。在 9 个月随访时,134 位婴儿中只有一人 HBV 呈阳性。结论 我们由护士主导的干预措施重点强调了将 HBV 的母婴传播预防纳入当前的产前保健部门的可行性,这是实施三重消除举措的基础。出生剂量的疫苗接种是实现消除 HBV 的关键所在。.На экспериментальной основе внедрить меры по профилактике передачи вируса гепатита В (HBV) от матери ребенку (ППМР) в дородовом и родильном отделении в г. Мапуту, Мозамбик, в течение 2017–2019 гг.Авторы включили HBV в существующую программу скринингового обследования (на вирус иммунодефицита человека (ВИЧ) и сифилис) беременных женщин во время их первой консультации и наблюдали за парами «мать-ребенок» на протяжении 9 месяцев после родов. Женщин с положительным результатом на поверхностный антиген вируса гепатита B (HBsAg) направляли на дальнейшее обследование, в том числе на определение HBe-антигена вируса гепатита В (HBeAg) и вирусную нагрузку HBV. По результатам обследований авторы предложили применение препарата «Тенофовир» для лечения или ППМР. Дозу вакцины против HBV вводили младенцам при рождении, а затем оценивали HBV-статус ребенка на протяжении 9 месяцев.Из 6775 женщин, прошедших скрининговое обследование, 270 (4,0%) имели положительный результат теста на HBsAg; среди тех, по которым имелись доступные данные, 24/265 (9,1%) имели положительный результат теста на HBeAg и 14/267 (5,2%) имели вирусную нагрузку 200 000 МЕ/мл. Девяносто восемь женщин (36,3%) с положительным результатом теста на HBsAg были ВИЧ-инфицированными, 97 из которых получали антиретровирусную терапию тенофовиром. Среди женщин с отрицательным диагнозом ВИЧ четыре имели показания для лечения тенофовиром, а четыре — для ППМР. Из 217 контактных живорожденных младенцев 181 (83,4%) получил вакцину против HBV при рождении, 160 (88,4%) из них менее чем через 24 часа после рождения. В период 9-месячного последующего наблюдения только у одного из 134 протестированных младенцев обнаружен вирус гепатита В.Меры с участием младшего медицинского персонала подчеркивают возможность практического внедрения ППМР HBV в работу существующих дородовых отделений и имеют важнейшее значение для реализации инициативы «тройной элиминации». Универсальная вакцинация дозой, вводимой ребенку при рождении, — это ключ к элиминации вируса гепатита B.

Background Cryptococcal meningitis is a leading cause of HIV-related mortality in sub-Saharan Africa, however, screening for cryptococcal antigenemia has not been universally implemented. As a result, data concerning cryptococcal meningitis and antigenemia are sparse, and in Mozambique, the prevalence of both are unknown. Methods We performed a retrospective analysis of routinely collected data from a point-of-care cryptococcal antigen screening program at a public hospital in Maputo, Mozambique. HIV-positive patients admitted to the emergency department underwent CD4 count testing; those with pre-defined abnormal vital signs or CD4 count ≤ 200 cells/μL received cryptococcal antigen testing and lumbar punctures if indicated. Patients with CM were admitted to the hospital and treated with liposomal amphotericin B and flucytosine; their 12-week outcomes were ascertained through review of medical records or telephone contact by program staff made in the routine course of service delivery. Results Among 1,795 patients screened for cryptococcal antigenemia between March 2018—March 2019, 134 (7.5%) were positive. Of patients with cryptococcal antigenemia, 96 (71.6%) were diagnosed with CM, representing 5.4% of all screened patients. Treatment outcomes were available for 87 CM patients: 24 patients (27.6%) died during induction treatment and 63 (72.4%) survived until discharge; of these, 38 (60.3%) remained in care, 9 (14.3%) died, and 16 (25.3%) were lost-to follow-up at 12 weeks. Conclusions We found a high prevalence of cryptococcal antigenemia and meningitis among patients screened at an emergency department in Maputo, Mozambique. High mortality during and after induction therapy demonstrate missed opportunities for earlier detection of cryptococcal antigenemia, even as point-of-care screening and rapid assessment in an emergency room offer potential to improve outcomes.

BackgroundKaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique.MethodsWe performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores ResultsAt 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4],p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD.DiscussionPLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.

Background HIV drug resistance (HIV-DR) is rising in sub-Saharan Africa in both ART-naive and ART-experienced patients. Objectives To estimate the level of acquired DR (ADR) and pre-treatment DR (PDR) across selected urban and rural sites in Southern Africa, in Mozambique. Methods We conducted two cross-sectional surveys among adult HIV patients (October 2017–18) assessing ADR and PDR. In the (ADR) survey, those on NNRTI-based first-line ART for ≥6 months were recruited (three sites). In the PDR survey, those ART-naive or experienced with ≥3 months of treatment interruption prior were enrolled (eight sites). Results Among 1113 ADR survey participants 83% were receiving tenofovir (TDF)/lamivudine (3TC)/efavirenz (EFV). The median time on ART was 4.5 years (Maputo) and 3.2 years (Tete), 8.3% (95% CI 6.2%-10.6%, Maputo) and 15.5% (Tete) had a VL ≥ 1000 copies/mL, among whom 66% and 76.4% had NNRTI+NRTI resistance, and 52.8% and 66.7% had 3TC+TDF-DR. Among those on TDF regimens, 31.1% (Maputo) and 42.2% (Tete) were still TDF susceptible, whereas 24.4% and 11.5% had TDF+zidovudine (ZDV)-DR. Among those on ZDV regimens, 25% and 54.5% had TDF+ZDV-DR. The PDR survey included 735 participants: NNRTI-PDR was 16.8% (12.0–22.6) (Maputo) and 31.2% (26.2–36.6) (Tete), with a higher proportion (≥50%) among those previously on ART affected by PDR. Conclusions In Mozambique, viral failure was driven by NNRTI and NRTI resistance, with NRTI DR affecting backbone options. NNRTI-PDR levels surpassed the WHO 10% ‘alert’ threshold. Replacing NNRTI first-line drugs is urgent, as is frequent viral load monitoring and resistance surveillance. Changing NRTI backbones when switching to second-line regimens may need reconsideration.

Adherence clubs (AC) offer patient-centred access to antiretroviral therapy (ART) while reducing the burden on health facilities. AC were implemented in a health centre in Mozambique specialising in patients with a history of HIV treatment failure. We explored the impact of AC on retention in care and VL suppression of these patients.We performed a retrospective analysis of patients enrolled in AC receiving second- or third-line ART. The Kaplan-Meier estimates were used to analyse retention in care in health facility, retention in AC and viral load (VL) suppression (VL 1000 copies/mL). Predictors of attrition and VL rebound (VL ≥ 1000 copies/mL) were assessed using multivariable proportional hazards regression.The analysed cohort contained 699 patients, median age 40 years [IQR: 35-47], 428 (61%) female and 97% second-line ART. Overall, 9 (1.3%) patients died, and 10 (1.4%) were lost to follow-up. Retention in care at months 12 and 24 was 98.9% (95% CI: 98.2-99.7) and 96.4% (95% CI: 94.6-98.2), respectively. Concurrently, 85.8% (95% CI: 83.1-88.2) and 80.9% (95% CI: 77.8-84.1) of patients maintained VL suppression. No association between predictors and all-cause attrition or VL rebound was detected. Among 90 patients attending AC and simultaneously having VL rebound, 64 (71.1%) achieved VL resuppression, 10 (11.1%) did not resuppress, and 14 (15.6%) had no subsequent VL result.Implementation of AC in Mozambique was successful and demonstrated that patients with a history of HIV treatment failure can be successfully retained in care and have high VL suppression rate when enrolled in AC. Expansion of the AC model in Mozambique could improve overall retention in care and VL suppression while reducing workload in health facilities.Les clubs d'adhésion (CA) offrent un accès centré sur le patient à la thérapie antirétrovirale (ART) tout en réduisant la charge des établissements de santé. Les CA ont été mis en œuvre dans un centre de santé au Mozambique spécialisé dans les patients ayant des antécédents d'échec du traitement du VIH. Nous avons exploré l'impact des CA sur la rétention dans les soins et la suppression de la CV chez ces patients. MÉTHODES: Nous avons effectué une analyse rétrospective des patients enrôlés dans les CA sous ART de deuxième ou troisième intention. Les estimations de Kaplan-Meyer ont été utilisées pour analyser la rétention dans les soins dans les établissements de santé, la rétention dans les CA et la suppression de la charge virale (CV) (CV1000 copies/mL). Les prédicteurs de l'attrition et du rebond de la CV (VL ≥ 1000 copies/mL) ont été évalués à l'aide d'une régression à risques proportionnels multivariés. RÉSULTATS: La cohorte analysée contenait 699 patients, d'âge médian 40 ans [IQR: 35-47], 428 (61%) femmes, 97% de traitement de deuxième intention. Dans l'ensemble, 9 (1,3%) patients sont décédés, 10 (1,4%) ont été perdus de vue. La rétention dans les soins à 12 et 24 mois était de 98,9% (IC95%: 98,2-99,7) et de 96,4% (IC95%: 94,6-98,2), respectivement. De même, 85,8% (IC95%: 83,1-88,2) et 80,9% (IC95%: 77,8-84,1) des patients ont maintenu une suppression de la CV. Aucune association entre les prédicteurs et l'attrition toutes causes ou le rebond de la CV n'a été détectée. Parmi 90 patients enrôlés dans les CA et ayant simultanément un rebond de la CV, 64 (71,1%) ont atteint une re-suppression de la CV, 10 (11,1%) n'ont pas atteint une re-suppression et 14 (15,6%) n'avaient pas de résultats de CV ultérieurs.La mise en œuvre des CA au Mozambique a été un succès et a démontré que les patients ayant des antécédents d'échec du traitement anti-VIH peuvent être retenus avec succès dans les soins et ont un taux élevé de suppression de la CV lorsqu'ils sont enrôlés dans les CA. L'expansion du modèle CA au Mozambique pourrait améliorer la rétention globale dans les soins et la suppression de la CV tout en réduisant la charge de travail dans les établissements de santé.

We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed. Keywords: Tuberculosis, Bedaquiline, Adverse events, Therapeutic index, Tolerability

A multicentric, retrospective case-series analysis (facility-based) in five sites across Kenya, Malawi, Mozambique, and Uganda screened HIV-positive adults for hepatitis C virus (HCV) antibodies using Oraquick rapid testing and viral confirmation (in three sites). The results reveal a substantially lower prevalence than previously reported for these countries, suggesting that targeted integration of HCV screening in African HIV programs may be more impactful than routine screening.

Introduction Viral load (VL) monitoring for people on antiretroviral therapy (ART) is extremely challenging in resource-limited settings. We assessed the VL testing scale-up in six Médecins Sans Frontières supported health centres in Maputo, Mozambique, during 2014–15. Methods In a retrospective cohort study, routine programme data were used to describe VL testing uptake and results, and multi-variate logistical regression to estimate predictors of VL testing uptake and suppression. Results Uptake of a first VL test was 40% (17 236/43 579). Uptake of a follow-up VL test for patients with a high first VL result was 35% (1095/3100). Factors associated with a higher uptake included: age below 15 years, longer time on ART and attending tailored service delivery platforms. Virological suppression was higher in pregnant/breastfeeding women and in community ART Group members. Patients with a high first VL result (18%; 3100/17 236) were mostly younger, had been on ART longer or had tuberculosis. Out of 1095 attending for a follow-up VL test, 678 (62%) had virological failure. Of those, less than one-third had started second line ART. Conclusion This was the first study describing the uptake and results of VL testing scale-up in Mozambique. Identified gaps show patient and programmatic challenges. Where service delivery was customized to patient needs, VL monitoring was more successful.

Increasing numbers of people living with HIV (PLHIV) in sub-Saharan Africa are experiencing failure of first-line antiretroviral therapy and transitioning onto second-line regimens. However, there is a dearth of research on their treatment experiences. We conducted in-depth interviews with 43 PLHIV on second- or third-line antiretroviral therapy and 15 HIV health workers in Kenya, Malawi and Mozambique to explore patients' and health workers' perspectives on these transitions. Interviews were audio-recorded, transcribed and translated into English. Data were coded inductively and analysed thematically. In all settings, experiences of treatment failure and associated episodes of ill-health disrupted daily social and economic activities, and recalled earlier fears of dying from HIV. Transitioning onto more effective regimens often represented a second (or third) chance to (re-)engage with HIV care, with patients prioritising their health over other aspects of their lives. However, many patients struggled to maintain these transformations, particularly when faced with persistent social challenges to pill-taking, alongside the burden of more complex regimens and an inability to mobilise sufficient resources to accommodate change. Efforts to identify treatment failure and support regimen change must account for these patients' unique illness and treatment histories, and interventions should incorporate tailored counselling and social and economic support.

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., Helena Huerga and colleagues assess a urine-based lipoarabinomannan assay for diagnosing tuberculosis in immunocompromised patients with HIV., Author summary Why was this study done? Tuberculosis (TB) is the leading cause of death in HIV-positive patients, but it remains difficult to diagnose. The availability of diagnostic tests is limited, and most require sputum samples, which are difficult to obtain from very sick patients. The lipoarabinomannan assay (LAM) is a urine-based point-of-care test that has shown utility in immunosuppressed HIV-positive patients. However, this test is not widely used. Current international guidelines recommend the use of the LAM test only in extremely immunocompromised HIV-positive, ambulatory patients. However, we hypothesized that the test could also be useful to diagnose TB in a broader group including less severely immunocompromised ambulatory patients. What did the researchers do and find? We conducted a prospective observational study in 6 health facilities in Malawi and Mozambique, enrolling HIV-positive, ambulatory patients with symptoms of TB. The clinicians conducted a clinical exam, requested diagnostic tests for TB (LAM in urine, microscopy, Xpert MTB/RIF assay [Xpert], culture in sputum, and chest radiography) at the first consultation, and followed the patients at subsequent visits over a 6-month period. Of the 456 enrolled patients, 205 (45%) had TB; of these, LAM was positive in 82.4% (169/205), microscopy in 33.7% (69/205), and Xpert in 40.0% (84/205). Using LAM in addition to the other available diagnostic tools increased the proportion of patients diagnosed with TB by 38.0% compared to a diagnostic algorithm including clinical exam, chest X-ray, and microscopy, and by 34.6% compared to an algorithm including clinical exam, chest X-ray, and Xpert. A similar increase was observed for less severely immunocompromised patients. What do these findings mean? The use of the urine-based LAM test can increase the proportion of immunocompromised HIV-positive patients diagnosed with TB, including patients who are less severely immunocompromised. LAM is useful in a broader population than what it is currently recommended for, and can be expanded for use in patients who are less severely immunocompromised.

Background Kaposi’s sarcoma (KS) is a common HIV-associated malignancy associated with disability, pain and poor outcomes. The cornerstone of its treatment is antiretroviral therapy, but advanced disease necessitates the addition of chemotherapy. In high-income settings, this often consists of liposomal anthracyclines, but in Mozambique, the first line includes conventional doxorubicin, bleomycin and vincristine, which is poorly-tolerated. Médecins Sans Frontières supports the Ministry of Health (MOH) in a specialized HIV and KS treatment center at the Centro de Referencia de Alto Maé in Maputo. Methods We performed a retrospective analysis of data collected on patients enrolled at the CRAM between 2010 and 2015, extracting routinely-collected clinical information from patient care databases. KS treatment followed national guidelines, and KS staging followed AIDS Clinical Trials Group and MOH criteria. Baseline description of the cohort and patient outcomes was performed. Risk factors for negative outcomes (death or loss to follow-up) were explored using Cox regression. Results Between 2010 and 2015, 1573 patients were enrolled, and 1210 began chemotherapy. A majority were young adult males. At enrollment, CD4 was

Objective : To describe long-term treatment outcomes of a pediatric HIV cohort in Mozambique. Design : Retrospective analysis of routine monitoring data. Setting : Secondary health care facilities in the Chamanculo Health District of Maputo. Subjects : A total of 1,335 antiretroviral treatment (ART) naive children

Background: In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment naïve patients. Methods: In this sub study, we explored the relationship of NNRTI concentrations with virological escape and the possible emergence of resistance mutations at week 48. The virological escape was defined as an HIV-RNA above 400 copies/m at week 48. Results: Among the 570 randomized patients, 470 (82%) had an HIV-RNA result at week 48; 54 (12.1%) patients had a viral escape and 35 patients had at least one major resistance mutation detected. Low drug concentration at weeks 12 and 24 (below the 10th percentile) were independently associated with virologic escape at week 48 (adjusted odds ratio [aOR]=2.9; 95% CI: 1.1 -7.2; p=0.0312 and aOR=4.2; 95% CI: 1.8-9.8; p=0.0019, respectively), and independently associated with an increased risk of emergence of resistance mutation (aOR=4.5; 95% CI: 1.8-14.6; p=0.009 at week 12; aOR=5.1; 95% CI: 1.8-14.6 at week 24). Receiver operating characteristic curves analyses indicated a better predictability of the mid-dose concentration and of the HIV-1 RNA values on resistance mutations in contrast to virological escape. Conclusions: Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug intake may prevent the occurrence of late virological escape and the selection of vial resistance mutations.

OBJECTIVE: To describe the frequency of diagnosis of cryptococcosis among HIV-infected patients in Phnom Penh, Cambodia, at programme entry, to investigate associated risk factors, and to determine the incidence of cryptococcal meningitis. METHODS: We analysed individual monitoring data from 11,970 HIV-infected adults enrolled between 1999 and 2008. We used Kaplan-Meier naive methods to estimate survival and retention in care and multiple logistic regression to investigate associations with individual-level factors. RESULTS: Cryptococcal meningitis was diagnosed in 12.0% of the patients: 1066 at inclusion and 374 during follow-up. Incidence was 20.3 per 1000 person-years and decreased over time. At diagnosis, median age was 33 years, median CD4 cell count was 8 cells/μl, and 2.4% of patients were receiving combined antiretroviral therapy; 38.7% died and 34.6% were lost to follow-up. Of 750 patients alive and in care after 3 months of diagnosis, 85.9% received secondary cryptococcal meningitis prophylaxis and 13.7% relapsed in median 5.7 months [interquartile range 4.1-8.8] after cryptococcal meningitis diagnosis (relapse incidence=5.7 per 100 person-years; 95%CI 4.7-6.9). Cryptococcal meningitis was more common in men at programme entry (adjusted OR=2.24, 95% CI 1.67-3.00) and fell with higher levels of CD4 cell counts (P

Background and objective : There are no recent data on the prevalence of drug-resistant tuberculosis (DR TB) in Cambodia. We aim to describe TB drug resistance amongst adults with pulmonary and extra-pulmonary TB and human immunodeficiency virus (HIV) co-infection in a national referral hospital in Phnom Penh, Cambodia. Design : Between 22 November 2007 and 30 November 2009, clinical specimens from HIV-infected patients suspected of having TB underwent routine microscopy, Mycobacterium tuberculosis culture, and drug susceptibility testing. Laboratory and clinical data were collected for patients with positive M. tuberculosis cultures. Results : M. tuberculosis was cultured from 236 HIV-infected patients. Resistance to any first-line TB drug occurred in 34.7% of patients; 8.1% had multidrug resistant tuberculosis (MDR TB). The proportion of MDR TB amongst new patients and previously treated patients was 3.7 and 28.9%, respectively ( p

To describe the frequency of diagnosis of cryptococcosis among HIV-infected patients in Phnom Penh, Cambodia, at programme entry, to investigate associated risk factors, and to determine the incidence of cryptococcal meningitis.We analysed individual monitoring data from 11,970 HIV-infected adults enrolled between 1999 and 2008. We used Kaplan-Meier naïve methods to estimate survival and retention in care and multiple logistic regression to investigate associations with individual-level factors.Cryptococcal meningitis was diagnosed in 12.0% of the patients: 1066 at inclusion and 374 during follow-up. Incidence was 20.3 per 1000 person-years and decreased over time. At diagnosis, median age was 33 years, median CD4 cell count was 8 cells/μl, and 2.4% of patients were receiving combined antiretroviral therapy; 38.7% died and 34.6% were lost to follow-up. Of 750 patients alive and in care after 3 months of diagnosis, 85.9% received secondary cryptococcal meningitis prophylaxis and 13.7% relapsed in median 5.7 months [interquartile range 4.1-8.8] after cryptococcal meningitis diagnosis (relapse incidence=5.7 per 100 person-years; 95%CI 4.7-6.9). Cryptococcal meningitis was more common in men at programme entry (adjusted OR=2.24, 95% CI 1.67-3.00) and fell with higher levels of CD4 cell counts (P0.0001).Cryptococcal meningitis remains an important cause of morbidity and mortality in Cambodian HIV-infected patients. Our findings highlight the importance of increasing early access to HIV care and cryptococcal meningitis prophylaxis and of improving its diagnosis in resource-limited settings.