Does timing of antiretroviral treatment influence treatment outcomes of visceral leishmaniasis in Northwest Ethiopia?

Background: Visceral leishmaniasis (VL) patients with HIV co-infection should receive antiretroviral treatment (ART). However, the best timing for initiation of ART is not known. Among such individuals, we assessed the influence of ART timing on VL outcomes. Methods: A retrospective cohort study was conducted in Northwest Ethiopia among VL patients starting ART between 2008 and 2015. VL outcomes were assessed by the twelfth month of starting ART, within 4 weeks of VL diagnosis or thereafter. Results: Of 213 VL-HIV co-infected patients with ART initiation, 96 (45.1%) had moderate to severe malnutrition, 53 (24.9%) had active TB and 128 (60.1%) had hemoglobin levels under 9 g/dL. Eighty-nine (41.8%) were already on ART before VL diagnosis, 46 (21.6%) started ART within 4 weeks, and 78 (36.6%) thereafter. Definitive cure in those starting ART within 4 weeks 59% (95% CI 43-75%) and those starting thereafter 56% (95% CI 44-68%) was not significantly different. Those starting ART before primary VL had higher 12-months mortality compared to those starting later (RR 0.6; 95% CI 0.4-0.9; p=0.012). Conclusions: VL-HIV patients are severely ill and with serious additional comorbidities. Outcomes of HIV-VL management are unsatisfactory and early ART initiation was associated with higher mortality. Further research on the optimal timing of ART initiation, and ensuring earlier diagnosis of VL patients, with improved management of comorbidities are needed.

Delivering HIV care in challenging operating environments: the MSF experience towards differentiated models of care for settings with multiple basic health care needs.

INTRODUCTION: Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic health care needs are multiple, systems are highly fragile and conflict disrupts health care. Médecins Sans Frontières (MSF) has been working to integrate HIV care in basic health services in such settings since 2000. We review the implementation of differentiated HIV care and treatment approaches in MSF-supported programmes in South Sudan (RoSS), Central African Republic (CAR) and Democratic Republic of Congo (DRC). METHODS: A descriptive analysis from CAR, DRC and RoSS programmes reviewing methodology and strategies of HIV care integration between 2010 and 2015 was performed. We describe HIV care models integrated within the provision of general health care and highlight best practices and challenges. RESULTS: Services included provision of general health care, with out-patient care (range between countries 43,343 and 287,163 consultations/year in 2015) and in-patient care (range 1076-16,595 in 2015). By the end of 2015 antiretroviral therapy (ART) initiations reached 12-255 patients/year. A total of 1101 and 1053 patients were on ART in CAR and DRC, respectively. In RoSS 186 patients were on ART when conflict recommenced late in 2013. While ART initiation and monitoring were mostly clinically driven in the early phase of the programmes, DRC implemented CD4 monitoring and progressively HIV viral load (VL) monitoring during study period. Attacks to health care facilities in CAR and RoSS disrupted service provision temporarily. Programmatic challenges include: competing health priorities influencing HIV care and need to integrate within general health services. Differentiated care approaches that support continuity of care in these programmes include simplification of medical protocols, multi-month ART prescriptions, and community strategies such as ART delivery groups, contingency plans and peer support activities. CONCLUSIONS: The principles of differentiated HIV care for high-quality ART delivery can successfully be applied in challenging operating environments. However, success heavily depends on specific adaptations to each setting.

Impact of HIV-associated conditions on mortality in people commencing anti-retroviral therapy in resource limited settings.

OBJECTIVES: To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010. SUBJECTS, PARTICIPANTS: 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55-2.27). OUTCOME MEASURES: Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation. RESULTS: There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21-5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97-2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74-4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), non-tuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80-3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80-3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary tuberculosis, Kaposi's sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates. CONCLUSIONS: A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for diagnostics, therapeutic interventions and research.

Association of BMI category change with TB treatment mortality in HIV-positive smear-negative and extrapulmonary TB patients in Myanmar and Zimbabwe.

OBJECTIVE: The HIV epidemic has increased the proportion of patients with smear-negative and extrapulmonary tuberculosis (TB) diagnoses, with related higher rates of poor TB treatment outcomes. Unlike in smear-positive pulmonary TB, no interim markers of TB treatment progress are systematically used to identify individuals most at risk of mortality. The objective of this study was to assess the association of body mass index (BMI) change at 1 month (±15 days) from TB treatment start with mortality among HIV-positive individuals with smear-negative and extrapulmonary TB. METHODS AND FINDINGS: A retrospective cohort study of adult HIV-positive new TB patients in Médecins Sans Frontières (MSF) treatment programmes in Myanmar and Zimbabwe was conducted using Cox proportional hazards regression to estimate the association between BMI category change and mortality. A cohort of 1090 TB patients (605 smear-negative and 485 extrapulmonary) was followed during TB treatment with mortality rate of 28.9 per 100 person-years. In multivariable analyses, remaining severely underweight or moving to a lower BMI category increased mortality (adjusted hazard ratio 4.05, 95% confidence interval 2.77-5.91, p<0.001) compared with remaining in the same or moving to a higher BMI category. CONCLUSIONS: We found a strong association between BMI category change during the first month of TB treatment and mortality. BMI category change could be used to identify individuals most at risk of mortality during TB treatment among smear-negative and extrapulmonary patients.