Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

Background: There are limited data on the failure of second-line antiretroviral therapy (ART) and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF) HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective: To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL) testing. Design: This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results: A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62%) responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0). No serious treatment-related adverse events were recorded. Conclusions: With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL monitoring and HIV genotype testing are currently major barriers to optimal management of patients failing second-line ART

Effect of previous utilization and out-of-pocket expenditure on subsequent utilization of a state led public-private partnership scheme "Chiranjeevi Yojana" to promote facility births in Gujarat, India

Background: In Gujarat, India, a state led public private partnership scheme to promote facility birth named Chiranjeevi Yojana (CY) was implemented in 2005. Institutional birth is provided free of cost at accredited private health facilities to women from socially disadvantaged groups (eligible women). CY has contributed in increasing facility birth and providing substantially subsidized (but not totally free) birth care; however, the retention of mothers in this scheme in subsequent child birth is unknown. Therefore, we conducted a study aimed to determine the effect of previous utilization of the scheme and previous out of pocket expenditure on subsequent child birth among multiparous eligible women in Gujarat.Methods: This was a retrospective cohort study of multiparous eligible women (after excluding abortions and births at public facility). A structured questionnaire was administered by trained research assistant to those with recent delivery between Jan and Jul 2013. Outcome of interest was CY utilization in subsequent child birth (Jan–Jul 2013). Explanatory variables included socio-demographic characteristics (including category of eligibility), pregnancy related characteristics in previous child birth, before Jan 2013, (including CY utilization, out of pocket expenditure) and type of child birth in subsequent birth. A poisson regression model was used to assess the association of factors with CY utilization in subsequent child birth.Results: Of 997 multiparous eligible women, 289 (29%) utilized and 708 (71%) did not utilize CY in their previous child birth. Of those who utilized CY (n = 289), 182 (63%) subsequently utilized CY and 33 (11%) gave birth at home; whereas those who did not utilize CY (n = 708) had four times higher risk (40% vs. 11%) of subsequent child birth at home. In multivariable models, previous utilization of the scheme was significantly associated with subsequent utilization (adjusted Relative Risk (aRR): 2.7; 95% CI: 2.2–3.3), however previous out of pocket expenditure was not found to be associated with retention in the CY scheme.Conclusion: Women with previous CY utilization were largely retained; therefore, steps to increase uptake of CY are expected to increase retention of mothers within CY in their subsequent child birth. To understand the reasons for subsequent child birth at home despite previous CY utilization and previous zero/minimal out of pocket expenditure, future research in the form of systematic qualitative enquiry is recommended

High survival and treatment success sustained after two and three years of first-line ART for children in Cambodia

ABSTRACT: BACKGROUND: Long-term outcomes of antiretroviral therapy (ART) in children remain poorly documented in resource-limited settings. The objective of this study was to assess two-and three-year survival, CD4 evolution and virological response among children on ART in a programmatic setting in Cambodia. METHODS: Children treated with first-line ART for at least 24 months were assessed with viral load testing and genotyping. We used Kaplan-Meier analysis for survival and Cox regression to identify risk factors associated with treatment failure. RESULTS: Of 1168 registered HIV-positive children, 670 (57%) started ART between January 2003 and December 2007. Survival probability was 0.93 (95% CI: 0.91-0.95) and 0.91 (95% CI: 0.88-0.93) at 24 and 36 months after ART initiation, respectively. Median CD4 gain for children aged over five years was 704 cells/mm3 at 24 months and 737 at 36 months. Median CD4 percentage gain for children under five years old was 15.2% at 24 months and 15% at 36 months. One hundred and thirty children completed at least 24 months of ART, and 138 completed 36 months: 128 out of 268 (48%) were female. Median age at ART initiation was six years.Overall, 22 children had viral loads of >1000 copies/ml (success ratio = 86% on intention-to-treat-analysis) and 21 of 21 presented mutations conferring resistance mostly to lamivudine and non-nucleoside reverse transcriptase inhibitors. Risk factors for failure after 24 and 36 months were CD4 counts below the threshold for severe immunosupression at those months respectively. Only two out of 22 children with viral loads of >1000 copies/ml met the World Health Organization immunological criteria for failure (sensitivity = 0.1). CONCLUSIONS: Good survival, immunological restoration and viral suppression can be sustained after two to three years of ART among children in resource-constrained settings. Increased access to routine virological measurements is needed for timely diagnosis of treatment failure

“When treatment is more challenging than the disease” : a qualitative study of MDR-TB patient retention.

CAPRISA, 2016.Abstract available in PDF file

Prevalence and risk factors for hepatitis C virus infection in an informal settlement in Karachi, Pakistan

The burden of hepatitis C virus (HCV) infection in Pakistan is amongst the highest in the world. People living in slums are likely to be at high risk of infection. Here, we describe the results of a cross-sectional survey conducted in March 2022 that aimed to quantify the prevalence of HCV infection in Machar Colony, one of the largest and oldest slum settlements in Karachi. Risk factors for HCV seropositivity were identified using multi-level logistic regression. We recruited 1,303 individuals in a random selection of 441 households from Machar Colony. The survey-adjusted HCV-seroprevalence was 13.5% (95% Confidence Interval (CI) 11.1–15.8) and survey-adjusted viraemic prevalence was 4.1% (95% CI 3.1–5.4) with a viraemic ratio of 32% (95% CI 24.3–40.5). Of 162 seropositive people, 71 (44%) reported receiving previous treatment for chronic hepatitis C. The odds of HCV seropositivity were found to increase with each additional reported therapeutic injection in the past 12 months (OR = 1.07 (95% Credible Interval (CrI) 1.00–1.13)). We found weaker evidence for a positive association between HCV seropositivity and a reported history of receiving a blood transfusion (OR = 1.72 (95% CrI 0.90–3.21)). The seroprevalence was more than double the previously reported seroprevalence in Sindh Province. The overall proportion of seropositive people that were viraemic was lower than expected. This may reflect the long-term impacts of a non-governmental clinic providing free of cost and easily accessible hepatitis C diagnosis and treatment to the population since 2015. Reuse of needles and syringes is likely to be an important driver of HCV transmission in this setting. Future public health interventions should address the expected risks associated with iatrogenic HCV transmission in this community

Ocular inflammatory disease and ocular tuberculosis in a cohort of patients co-infected with HIV and multidrug-resistant tuberculosis in Mumbai, India: a cross-sectional study.

The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART)

Recurrent tuberculosis and associated factors : a five-year countrywide study in Uzbekistan

Background:  In Uzbekistan, despite stable and relatively high tuberculosis treatment success rates, relatively high rates of recurrent tuberculosis have recently been reported. Recurrent tuberculosis is when a patient who was treated for pulmonary tuberculosis and cured, later develops the disease again. This requires closer analysis to identify possible causes and recommend interventions to improve the situation. Using countrywide data, this study aimed to analyse trends in recurrent tuberculosis cases and describe their associations with socio-demographic and clinical factors. Method:  Countrywide retrospective cohort study comparing recurrent tuberculosis patients with all new tuberculosis patients registered within the NTP between January 2006 and December 2010 using routinely collected data. Determinants studied were baseline characteristics and treatment outcomes. Results:  Of 107,380 registered patients during the period January 2006 and December 2010, 9358 (8.7%) were recurrent cases. Between 2006 and 2008, the number of recurrent cases per annum increased from 1530 to 2081, then fell slightly thereafter from 2081 to 1888 cases. The proportion of all notified cases during this period increased from 6.5% to 9.9%. Factors associated with recurrent tuberculosis included age (35–55 years old), having smear positive pulmonary tuberculosis, residing in certain areas of Uzbekistan, having particular co-morbidities (including chronic obstructive pulmonary disease and HIV), and being unemployed, a pensioner or disabled. Recurrent tuberculosis patients also had a higher likelihood of having an unfavourable treatment outcome. Conclusion:  Despite signs of declining national tuberculosis notifications between 2006 and 2010, the relative proportion of recurrent cases appears to have increased. These findings, together with the identification of possible risk factors associated with recurrent tuberculosis, highlight various areas where Uzbekistan needs to focus its tuberculosis control efforts, particularly in light of the country’s rapidly emerging multi drug resistant tuberculosis epidemic.Publisher PDFPeer reviewe

Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India.

BACKGROUND: There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen. METHODS: This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART). RESULTS: 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4-18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse. CONCLUSIONS: In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients

Improving pediatric TB diagnosis in North Kivu (DR Congo), focusing on a clinical algorithm including targeted Xpert MTB/RIF on gastric aspirates

Background The incidence of tuberculosis (TB) in the Democratic Republic of the Congo (DRC) is 323/100,000. A context of civil conflict, internally displaced people and mining activities suggests a higher regional TB incidence in North Kivu. Medecins Sans Frontieres (MSF) supports the General Reference Hospital of Masisi, North Kivu, covering a population of 520,000, with an elevated rate of pediatric malnutrition. In July 2017, an adapted MSF pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates (GAs), was implemented. The aim of this study was to evaluate whether the introduction of this clinical pediatric TB diagnostic algorithm influenced the number of children started on TB treatment. Methods We performed a retrospective analysis of pediatric TB cases started on treatment in the inpatient therapeutic feeding centre (ITFC) and the pediatric ward. We compared data collected in the second half (July to December) of 2016 (before introduction of the new diagnostic algorithm) and the second half of 2017. For the outcome variables the difference between the two years was calculated by a Pearson Chi-square test. Results In 2017, 94 GAs were performed, compared to none in 2016. Twelve percent (11/94) of samples were Xpert MTB/RIF positive. Sixty-eight children (2.9% of total exits) aged between 3 months and 15 years started TB treatment in 2017, compared to 19 (1.4% of total exits) in 2016 (p 0.002). The largest increase in pediatric TB diagnoses in 2017 occurred in patients with a negative Xpert MTB/RIF result, but clinically highly suggestive of TB according to the newly introduced diagnostic algorithm. Fifty-two (3.1%) children under five years old started treatment in 2017, as compared to 14 (1.3%) in 2016 (p 0.004). The increase was less pronounced and not statistically significant in older patients: sixteen children (2.6%) above 5 years old started TB treatment in 2017 as compared to five (1.3%) in 2016 (p 0.17). Conclusion After the introduction of an adapted clinical pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates, we observed a significant increase in the number of children - especially under 5 years old - started on TB treatment, mostly on clinical grounds. Increased 'clinician awareness' of pediatric TB likely played an important role