Factors associated with adverse outcomes among patients hospitalized at a COVID-19 treatment center in Herat, Afghanistan.

Though many studies on COVID have been published to date, data on COVID-19 epidemiology, symptoms, risk factors and severity in low- and middle-income countries (LMICS), such as Afghanistan are sparse. To describe clinical characteristics, severity, and outcomes of patients hospitalized in the MSF COVID-19 treatment center (CTC) in Herat, Afghanistan and to assess risk factors associated with severe outcomes. 1113 patients were included in this observational study between June 2020 and April 2022. Descriptive analysis was performed on clinical characteristics, complications, and outcomes of patients. Univariate description by Cox regression to identify risk factors for an adverse outcome was performed. Adverse outcome was defined as death or transfer to a level 3 intensive care located at another health facility. Finally, factors identified were included in a multivariate Cox survival analysis. A total of 165 patients (14.8%) suffered from a severe disease course, with a median time of 6 days (interquartile range: 2-11 days) from admission to adverse outcome. In our multivariate model, we identified male gender, age over 50, high O2 flow administered during admission, lymphopenia, anemia and O2 saturation < = 93% during the first three days of admission as predictors for a severe disease course (p<0.05). Our analysis concluded in a relatively low rate of adverse outcomes of 14.8%. This is possibly related to the fact that the resources at an MSF-led facility are higher, in terms of human resources as well as supply of drugs and biomedical equipment, including oxygen therapy devices, compared to local hospitals. Predictors for severe disease outcomes were found to be comparable to other settings.

HIV, sexual violence, and termination of pregnancy among adolescent and adult female sex workers in Malawi: A respondent-driven sampling study.

Female Sex Workers (FSWs) are a hard-to-reach and understudied population, especially those who begin selling sex at a young age. In one of the most economically disadvantaged regions in Malawi, a large population of women is engaged in sex work surrounding predominantly male work sites and transport routes. A cross-sectional study in February and April 2019 in Nsanje district used respondent driven sampling (RDS) to recruit women ≥13 years who had sexual intercourse (with someone other than their main partner) in exchange for money or goods in the last 30 days. A standardized questionnaire was filled in; HIV, syphilis, gonorrhea, and chlamydia tests were performed. CD4 count and viral load (VL) testing occurred for persons living with HIV (PLHIV). Among 363 study participants, one-quarter were adolescents 13-19 years (25.9%; n = 85). HIV prevalence was 52.6% [47.3-57.6] and increased with age: from 14.7% (13-19 years) to 87.9% (≥35 years). HIV status awareness was 95.2% [91.3-97.4], ART coverage was 98.8% [95.3-99.7], and VL suppression 83.2% [77.1-88.0], though adolescent FSWs were less likely to be virally suppressed than adults (62.8% vs. 84.4%). Overall syphilis prevalence was 29.7% [25.3-43.5], gonorrhea 9.5% [6.9-12.9], and chlamydia 12.5% [9.3-16.6]. 72.4% had at least one unwanted pregnancy, 17.9% had at least one abortion (40.1% of which were unsafe). Half of participants reported experiencing sexual violence (SV) (47.6% [42.5-52.7]) and more than one-tenth (14.2%) of all respondents experienced SV perpetrated by a police officer. Our findings show high levels of PLHIV-FSWs engaged in all stages of the HIV cascade of care. The prevalence of HIV, other STIs, unwanted pregnancy, unsafe abortion, and sexual violence remains extremely high. Peer-led approaches contributed to levels of ART coverage and HIV status awareness similar to those found in the general district population, despite the challenges and risks faced by FSWs.

High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients.

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.

Implementation and operational feasibility of SAMBA I HIV-1 semi-quantitative viral load testing at the point-of-care in rural settings in Malawi and Uganda.

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.

OBJECTIF: Nous avons suivi une mise en œuvre à grande échelle du test de la charge virale semi-quantitative du VIH -1 basé sur de Test de Simple Amplification version I (SAMBA I Viral Load = SAMBA I VL) au sein des programmes VIH de Médecins Sans Frontières au Malawi et en Ouganda, afin d'évaluer sa performance et sa faisabilité opérationnelle. MÉTHODES: Analyse descriptive des données du programme de routine entre août 2013 et décembre 2016. L'ensemble des données comprenait des échantillons collectés pour le suivi de la CV et testés à l'aide de SAMBA I VL dans cinq cliniques VIH au Malawi (quatre centres de santé périphériques et un hôpital de district), et une clinique VIH dans un hôpital régional de référence en Ouganda. SAMBA I VL a été utilisé pour le test de la CV chez les patients qui recevaient l'ART depuis 6 mois à dix ans, afin de déterminer si la CV plasmatique était supérieure ou inférieure à 1000 copies/ml de VIH-1, reflétant l'échec ou l'efficacité de l'ART. Des échantillons sélectionnés aléatoirement ont été quantifiés avec des tests de CV commerciaux. Les instruments de SAMBA I et les performances des tests, le débit du site et les délais dans la communication des résultats aux cliniciens et aux patients ont été suivis. RÉSULTATS: Entre août 2013 et décembre 2016, un total de 60.889 échantillons de patients ont été analysés avec SAMBA I VL. Dans l'ensemble, 0,23% des résultats initiaux de SAMBA I VL étaient invalides; ceux-ci ont été été réduits à 0,04% après avoir répété le test une fois. L'échec global du test, y compris l'échec de l'instrument, était de 1,34%. La concordance avec les tests quantitatifs de référence de la CV était de 2620/2727; 96,0% (1338/1382; 96,8% au Malawi; 1282/1345; 95,3% en Ouganda). Pour les centres de santé périphériques de Chiradzulu et la clinique VIH de l'hôpital d'Arua, où les tests ont été effectués sur place, les résultats ont été communiqués le jour même aux cliniciens pour entre 91% et 97% des échantillons. Un examen clinique le jour même a été obtenu pour 84,7% de l'ensemble des échantillons testés. CONCLUSIONS: Le test SAMBA I VL est réalisable pour le suivi de cohortes de 1.000 à 5.000 patients déjà sous ART. Les résultats le jour même peuvent être utilisés pour éclairer la prise de décision clinique rapide dans les établissements de santé ruraux et éloignés, réduisant potentiellement le temps disponible pour le développement de la résistance et contribuant éventuellement à réduire la morbidité et la mortalité.

Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi.

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.

Pediatric Access and Continuity of HIV Care Before the Start of Antiretroviral Therapy in Sub-Saharan Africa.

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.

Risk factors and mortality associated with resistance to first-line antiretroviral therapy: multicentric cross-sectional and longitudinal analyses.

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.

Outcomes of antiretroviral therapy over a 10-year period of expansion: a multicohort analysis of African and Asian HIV programs.

OBJECTIVE: Little is known about the evolution of program outcomes associated with rapid expansion of antiretroviral therapy (ART) in resource-limited settings. We describe temporal trends and assess associations with mortality and loss to follow-up (LTFU) in HIV cohorts from 8 countries. DESIGN: Multicohort study using electronic health records. METHODS: Analysis included adults in 25 Médecins Sans Frontières-supported programs initiating ART between 2001 and 2011. Kaplan-Meier methods were used to describe time to death or LTFU and proportional hazards models to assess associations with individual and program factors. RESULTS: ART programs (n = 132,334, median age 35 years, 61% female) expanded rapidly. Whereas 36-month mortality decreased from 22% to 9% over 5 years (≤2003-2008), LTFU increased from 11% to 21%. Hazard ratios (HR) of early (0-12 months) and late (12-72 months) LTFU increased over time, from 1.09 [95% confidence interval (CI): 0.83 to 1.43] and 1.04 (95% CI: 0.84 to 1.28) in 2004 to 3.29 (95% CI: 2.42 to 4.46) and 6.86 (95% CI: 4.94 to 9.53) in 2011, compared with 2001-2003. Rate of program expansion was strongly associated with increased early and late LTFU, adjusted HR (aHR) = 2.31 (95% CI: 1.78 to 3.01) and HR = 2.29 (95% CI: 1.76 to 2.99), respectively, for ≥125 vs. 0-24 patients per month. Larger program size was associated with decreased early mortality (aHR = 0.49, 95% CI: 0.31 to 0.77 for ≥20,000 vs. <500 patients) and increased early LTFU (aHR = 1.77, 95% CI: 1.04 to 3.04 for ≥20,000 vs. <500 patients). CONCLUSIONS: As ART expands in resource-limited settings, challenges remain in improving access to ART and preventing program attrition. There is an urgent need for novel and sustainable models of care to increase long-term retention of patients.

Adults receiving HIV care before the start of antiretroviral therapy in sub-Saharan Africa: patient outcomes and associated risk factors.

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.

Paediatric HIV care in sub-Saharan Africa: clinical presentation and 2-year outcomes stratified by age group.

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.

Evaluation of three sampling methods to monitor outcomes of antiretroviral treatment programmes in low- and middle-income countries.

BACKGROUND: Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Médecins Sans Frontières), we evaluated three sampling approaches to simplify the generation of outcome indicators. METHODS AND FINDINGS: We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5(th) and 97.5(th) percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9-88.6) and the proportion of patients LFU, 13.5% (range 0.8-31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4-77.7) for random, 76.5% (75.3-77.5) for systematic and 76.0% (74.1-78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6-14.5), 13.5% (12.6-14.3) and 14.0% (12.5-15.5), respectively. With consecutive sampling, 50% of sites had SD within ±5% of the unsampled site value. CONCLUSIONS: Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites.