HIV-1 co-infection increases relapse rate and shortens survival in patients with visceral leishmaniasis

Visceral leishmaniasis (VL) and HIV co-infection (VL/HIV) has emerged as a significant public health problem in Ethiopia, with up to 30% of VL patients co-infected with HIV. These patients suffer from recurrent VL relapses and increased mortality. Our aim was to assess whether VL/HIV co-infected patients with a previous history of VL relapses (recurrent VL/HIV) have a poorer prognosis as compared to HIV patients presenting with their first episode of VL (primary VL/HIV). Our results show that recurrent VL/HIV patients have a higher parasite load, higher mortality and that their relapse-free survival is significantly shorter. The poorer prognosis of recurrent VL/HIV patients is accompanied by lower weight gain and lower recovery of all blood cell lineages, as well as lower production of IFN{gamma}, lower CD4+ T cell counts and higher expression levels of PD1 on T cells. Furthermore, our results show that prior history of VL relapse is an important risk factor for future relapse. Both CD4+ T cell count and parasite load were also associated with a higher risk of VL relapse, but neither of these was independently associated with relapse risk after adjustment for previous VL relapse history. We propose that in addition to the current treatments, novel interventions should be considered at the time of VL diagnosis in VL/HIV patients; and suggest that improved anti-leishmanial and antiretroviral treatments, as well as immune therapy, through PD1/PDL-1 blockade and/or through IFN{gamma} administration, could result in more efficient parasite killing and thereby reduce the relapse rate and improve survival.