Journal Article > ResearchFull Text
Clin Infect Dis. 15 October 2022; Volume 75 (Issue 8); 1423-1432.; DOI:10.1093/cid/ciac127
Burza S, Mahajan R, Kazmi S, Alexander N, Kumar D, et al.
Clin Infect Dis. 15 October 2022; Volume 75 (Issue 8); 1423-1432.; DOI:10.1093/cid/ciac127
BACKGROUND
Visceral leishmaniasis (VL) in patients living with Human-Immunodeficiency-Virus (HIV) present an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian sub-continent.
METHODS
This is a randomised open label, parallel arm phase-3 trial conducted within a single hospital in Patna, India. 150 patients aged =18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to one of two treatment arms, either a total 40mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 8 equal doses over 24-days, or a total 30mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 6 equal doses given concomitantly with a total 1.4g oral miltefosine administered through two daily doses of 50mg over 14-days. The primary outcome was ITT relapse-free-survival at day-210, defined as absence of signs and symptoms of VL, or if symptomatic negative parasitological investigations.
FINDINGS
Among 243 patients assessed for eligibility, 150 were recruited between 2nd January 2017 and 5th April 2018, with no loss-to-follow-up. Relapse free survival at day-210 was 85%, (64/75; 95%CI 77-100) in the monotherapy arm, and 96%, (72/75;95%CI 90-100) in the combination arm. 19%(28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse free survival at day-210 was 90%, (55/61;95%CI 82-100) in the monotherapy and 97%, (59/61;95%CI 91-100) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm.
CONCLUSIONS
Combination therapy appears to be safe, well tolerated and effective, and halves treatment duration of current recommendations.
Visceral leishmaniasis (VL) in patients living with Human-Immunodeficiency-Virus (HIV) present an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian sub-continent.
METHODS
This is a randomised open label, parallel arm phase-3 trial conducted within a single hospital in Patna, India. 150 patients aged =18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to one of two treatment arms, either a total 40mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 8 equal doses over 24-days, or a total 30mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 6 equal doses given concomitantly with a total 1.4g oral miltefosine administered through two daily doses of 50mg over 14-days. The primary outcome was ITT relapse-free-survival at day-210, defined as absence of signs and symptoms of VL, or if symptomatic negative parasitological investigations.
FINDINGS
Among 243 patients assessed for eligibility, 150 were recruited between 2nd January 2017 and 5th April 2018, with no loss-to-follow-up. Relapse free survival at day-210 was 85%, (64/75; 95%CI 77-100) in the monotherapy arm, and 96%, (72/75;95%CI 90-100) in the combination arm. 19%(28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse free survival at day-210 was 90%, (55/61;95%CI 82-100) in the monotherapy and 97%, (59/61;95%CI 91-100) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm.
CONCLUSIONS
Combination therapy appears to be safe, well tolerated and effective, and halves treatment duration of current recommendations.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 30 August 2022; Volume 16 (Issue 8); e0010718.; DOI:10.1371/journal.pntd.0010718
Mahajan R, Owen SI, Kumar S, Pandey K, Kazmi S, et al.
PLoS Negl Trop Dis. 30 August 2022; Volume 16 (Issue 8); e0010718.; DOI:10.1371/journal.pntd.0010718
People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen’s Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33–46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts <100 (OR 3.1; 95% CI 1.2–7.6) and CD4 counts 100–199 (OR = 2.1;95% CI:1.1–4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR = 1.9;95% CI:1.1–3.1). A total of 2.2% (n = 28) participants were positive by Leishmania antigen ELISA, detecting 20 additional participants to the asymptomatic cohort. Prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. Using the Leishmania antigen ELISA, prevalence increased to 9.0%. Patients with low CD4 counts and larger household size were found to have significantly higher risk of ALI.
Conference Material > Slide Presentation
Mahajan R, Owen SI, Kumar S, Kazmi S, Das P, et al.
MSF Scientific Days International 2021: Research. 19 May 2021
Conference Material > Abstract
Mahajan R, Owen SI, Kumar S, Kazmi S, Das P, et al.
MSF Scientific Days International 2021: Research. 19 May 2021
INTRODUCTION
People co-infected with visceral leishmaniasis and HIV (VL-HIV) typically present with advanced HIV disease and in poor clinical condition. The reasons for this are complex, but one major challenge relates to difficulties in ensuring early diagnosis of VL, a stage IV opportunistic infection, in the context of HIV. In VL-endemic areas, it is recognised that between 2 and 20% of the general population may harbour asymptomatic Leishmania infection (ALI), the vast majority of whom will not progress to symptomatic disease. However, similar data are absent for people living with HIV (PLHIV) in South Asia. Being able to diagnose ALI may provide a screen-and-treat opportunity to prevent progression to the fatal symptomatic form. We investigated the prevalence and determinants of ALI in PLHIV living in VL-endemic areas, and the risk of progression to symptomatic VL.
METHODS
We conducted a cross-sectional survey, enrolling PLHIV aged ≥18 with no diagnosis of or history of leishmaniasis symptoms, at three antiretroviral therapy centres within VL-endemic regions of Bihar, India. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT), and/or quantitative polymerase chain reaction (qPCR) result on blood. In addition, we tested for the Leishmania antigen in urine using ELISA as a novel non-invasive alternative. Participants were followed up at three-monthly intervals over 18 months to assess status and progression to symptomatic infection.
ETHICS
This study was approved by the ethics boards of the Rajendra Memorial Research Institute of Medical Sciences, Patna, India, and Liverpool School of Tropical Medicine, UK, and the MSF Ethics Review Board. Clinical Trial Registry-India number, CTRI/2017/03/008120.
RESULTS
1,296 PLHIV were included in the analysis. The baseline prevalence of ALI was 7.4% (n=96). All were found positive using rK39 ELISA, while 0.5% (n=6) and 0.4% (n=5) were positive using qPCR and rK39 RDT, respectively. 2.2% (n=28) patients were positive using urinary Leishmania antigen ELISA testing. Independent risk factors (p<0.05) for ALI were CD4 count <100 cells/mm3 (adjusted odds ratio, aOR, 3.1; 95%CI 1.2-7.6), and CD4 count between 100-199 cells/mm3 (aOR=2.1; 95%CI 1.1-4.0), as compared to CD4 ≥300 cells/mm3 and living in a household size ≥5 (aOR=1.8; 95%CI 1.1-3.2). Concordance between diagnostic tests was poor. A total of 109 asymptomatic patients were followed up prospectively, including 13 additional patients who were identified during pilot testing. Overall, 3.7% (n=4) patients converted from asymptomatic to symptomatic infection over the study period. Conversion rates of participants identified as positive using rK39 ELISA, rK39 RDT, qPCR, and urinary Leishmania antigen ELISA, were 3.7% (4/109), 40% (2/5), 57% (4/7), and 14% (4/29), respectively. Risk of all-cause mortality in those with ALI over 18 months’ follow-up was 6.4% (n=7), compared with 2.5% (n=30) in those without (risk ratio, 2.6, 95%CI 1.2-5.7, p=0.018).
CONCLUSION
PLHIV living in highly VL-endemic areas have a relatively high prevalence of ALI. Although progression rates to symptomatic infection appear low, all-cause mortality rates are higher and may reflect the impact of sub-clinical infection on HIV outcomes. The results may justify further studies investigating early treatment of ALI in PLHIV.
People co-infected with visceral leishmaniasis and HIV (VL-HIV) typically present with advanced HIV disease and in poor clinical condition. The reasons for this are complex, but one major challenge relates to difficulties in ensuring early diagnosis of VL, a stage IV opportunistic infection, in the context of HIV. In VL-endemic areas, it is recognised that between 2 and 20% of the general population may harbour asymptomatic Leishmania infection (ALI), the vast majority of whom will not progress to symptomatic disease. However, similar data are absent for people living with HIV (PLHIV) in South Asia. Being able to diagnose ALI may provide a screen-and-treat opportunity to prevent progression to the fatal symptomatic form. We investigated the prevalence and determinants of ALI in PLHIV living in VL-endemic areas, and the risk of progression to symptomatic VL.
METHODS
We conducted a cross-sectional survey, enrolling PLHIV aged ≥18 with no diagnosis of or history of leishmaniasis symptoms, at three antiretroviral therapy centres within VL-endemic regions of Bihar, India. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT), and/or quantitative polymerase chain reaction (qPCR) result on blood. In addition, we tested for the Leishmania antigen in urine using ELISA as a novel non-invasive alternative. Participants were followed up at three-monthly intervals over 18 months to assess status and progression to symptomatic infection.
ETHICS
This study was approved by the ethics boards of the Rajendra Memorial Research Institute of Medical Sciences, Patna, India, and Liverpool School of Tropical Medicine, UK, and the MSF Ethics Review Board. Clinical Trial Registry-India number, CTRI/2017/03/008120.
RESULTS
1,296 PLHIV were included in the analysis. The baseline prevalence of ALI was 7.4% (n=96). All were found positive using rK39 ELISA, while 0.5% (n=6) and 0.4% (n=5) were positive using qPCR and rK39 RDT, respectively. 2.2% (n=28) patients were positive using urinary Leishmania antigen ELISA testing. Independent risk factors (p<0.05) for ALI were CD4 count <100 cells/mm3 (adjusted odds ratio, aOR, 3.1; 95%CI 1.2-7.6), and CD4 count between 100-199 cells/mm3 (aOR=2.1; 95%CI 1.1-4.0), as compared to CD4 ≥300 cells/mm3 and living in a household size ≥5 (aOR=1.8; 95%CI 1.1-3.2). Concordance between diagnostic tests was poor. A total of 109 asymptomatic patients were followed up prospectively, including 13 additional patients who were identified during pilot testing. Overall, 3.7% (n=4) patients converted from asymptomatic to symptomatic infection over the study period. Conversion rates of participants identified as positive using rK39 ELISA, rK39 RDT, qPCR, and urinary Leishmania antigen ELISA, were 3.7% (4/109), 40% (2/5), 57% (4/7), and 14% (4/29), respectively. Risk of all-cause mortality in those with ALI over 18 months’ follow-up was 6.4% (n=7), compared with 2.5% (n=30) in those without (risk ratio, 2.6, 95%CI 1.2-5.7, p=0.018).
CONCLUSION
PLHIV living in highly VL-endemic areas have a relatively high prevalence of ALI. Although progression rates to symptomatic infection appear low, all-cause mortality rates are higher and may reflect the impact of sub-clinical infection on HIV outcomes. The results may justify further studies investigating early treatment of ALI in PLHIV.
Journal Article > CommentaryFull Text
BMJ Open. 25 November 2019; Volume 9 (Issue 11); DOI:10.1136/bmjopen-2019-033790
Nair MM, Kumar P, Pandey S, Harshana A, Kazmi S, et al.
BMJ Open. 25 November 2019; Volume 9 (Issue 11); DOI:10.1136/bmjopen-2019-033790
OBJECTIVES:
This study aimed to explore barriers to accessing care, if any, among people living with HIV/AIDS (PLHA) in two districts of Bihar. We also aimed to assess attitudes towards PLHA among healthcare providers and community members.
DESIGN:
This qualitative study used an exploratory study design through thematic analysis of semistructured, in-depth interviews.
SETTING:
Two districts were purposively selected for the study, namely the capital Patna and a peripheral district located approximately 100 km from Patna, in order to glean insights from a diverse sample of respondents.
PARTICIPANTS:
Our team purposively selected 71 participants, including 35 PLHA, 10 community members and 26 healthcare providers.
RESULTS:
The overarching theme that evolved from these data through thematic coding identified that enacted stigma and discrimination interfere with each step in the HIV care continuum for PLHA in Bihar, India, especially outside urban areas. The five themes that contributed to these results include: perception of HIV as a dirty illness at the community level; non-consensual disclosure of HIV status; reliance on identifying PLHA to guide procedures and resistance to universal precautions; refusal to treat identified PLHA and referrals to other health centres for treatment; and inadequate knowledge and fear among health providers with respect to HIV transmission.
CONCLUSIONS:
The continued presence of discriminatory and stigmatising attitudes towards PLHA negatively impacts both disclosure of HIV status as well as access to care and treatment. We recognise a pressing need to improve the knowledge of HIV transmission, and implement universal precautions across all health facilities in the state, not just to reduce stigma and discrimination but also to ensure proper infection control. In order to improve treatment adherence and encourage optimal utilisation of services, it is imperative that the health system invest more in stigma reduction in Bihar and move beyond more ineffective, punitive approaches.
This study aimed to explore barriers to accessing care, if any, among people living with HIV/AIDS (PLHA) in two districts of Bihar. We also aimed to assess attitudes towards PLHA among healthcare providers and community members.
DESIGN:
This qualitative study used an exploratory study design through thematic analysis of semistructured, in-depth interviews.
SETTING:
Two districts were purposively selected for the study, namely the capital Patna and a peripheral district located approximately 100 km from Patna, in order to glean insights from a diverse sample of respondents.
PARTICIPANTS:
Our team purposively selected 71 participants, including 35 PLHA, 10 community members and 26 healthcare providers.
RESULTS:
The overarching theme that evolved from these data through thematic coding identified that enacted stigma and discrimination interfere with each step in the HIV care continuum for PLHA in Bihar, India, especially outside urban areas. The five themes that contributed to these results include: perception of HIV as a dirty illness at the community level; non-consensual disclosure of HIV status; reliance on identifying PLHA to guide procedures and resistance to universal precautions; refusal to treat identified PLHA and referrals to other health centres for treatment; and inadequate knowledge and fear among health providers with respect to HIV transmission.
CONCLUSIONS:
The continued presence of discriminatory and stigmatising attitudes towards PLHA negatively impacts both disclosure of HIV status as well as access to care and treatment. We recognise a pressing need to improve the knowledge of HIV transmission, and implement universal precautions across all health facilities in the state, not just to reduce stigma and discrimination but also to ensure proper infection control. In order to improve treatment adherence and encourage optimal utilisation of services, it is imperative that the health system invest more in stigma reduction in Bihar and move beyond more ineffective, punitive approaches.
Journal Article > CommentaryFull Text
Indian J Public Health. 14 June 2018; DOI:10.4103/ijph.IJPH_386_16
Faizi N, Kumar AMV, Kazmi S
Indian J Public Health. 14 June 2018; DOI:10.4103/ijph.IJPH_386_16