Abstract
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.
