Effect of schistosomiasis on the outcome of patients infected with HIV-1 starting antiretroviral therapy in rural Tanzania

Background It has been hypothesized that schistosomiasis negatively influences immune reconstitution in people living with HIV starting antiretroviral therapy (ART). In this study, we investigated the effect of schistosomiasis on the course of HIV infection in patients starting ART in a rural part of Tanzania. Methodology Retrospective study including patients prospectively enrolled in a HIV cohort in Ifakara, south-central Tanzania between January 1, 2013 and April 1, 2015. Schistosomal circulating anodic antigen (CAA) was assessed in pre-ART cryopreserved plasma. Regression models were utilized to estimate the effect of CAA positivity on virological and immunological failure and a composite outcome of death/loss to follow-up (LFU). Principal findings At ART-initiation 19.1% (88/461) of patients were CAA-positive. A tendency of higher CD4 increases was seen in CAA-positive patients (+182 cells/μl, interquartile range (IQR), 87–285 cells/μl) compared to CAA-negative patients (+147 cells/μl, IQR, 55–234 cells/μl, p = 0.09) after 10 months of follow-up. After adjustment for baseline risk factors, CAA-positivity showed no association with virological or immunological failure. In CAA-positive patients, 22.7% (20/88) died or were LFU, compared to 29.5% (110/373) of CAA-negative patients (hazard ratio (HR): 0.76, 95% confidence interval (CI), 0.47–1.22, p = 0.25). After adjustment for age, sex, body mass index, educational attainment, WHO-stage, tuberculosis status, and year of ART initiation, CAA-positivity showed a trend of a decreased hazard of death/LFU (HR: 0.58, 95% CI: 0.32–1.05, p = 0.07), while CD4 count at baseline (HR: 0.86, 95% CI: 0.76–1.00, p = 0.02) and MXD (sum of eosinophils, basophils, and monocytes counts) >1,100 cells/μl (HR: 0.56, 95% CI: 0.34–0.93, p = 0.03) were identified as independently protective factors. Conclusions/Significance Schistosomiasis is prevalent in this HIV cohort and may be beneficial for immunological reconstitution, while no effect on virological failure was apparent. A positive effect of schistosomiasis-induced immunomodulation on survival and retention in care needs confirmation in future studies.

[1]  P. Corstjens,et al.  Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: A nested case-control study , 2017, PLoS neglected tropical diseases.

[2]  J. Utzinger,et al.  Accuracy of Diagnostic Tests for Schistosoma mansoni Infection in Asymptomatic Eritrean Refugees: Serology and Point-of-Care Circulating Cathodic Antigen Against Stool Microscopy , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[3]  M. Tanner,et al.  A decade of HIV care in rural Tanzania: Trends in clinical outcomes and impact of clinic optimisation in an open, prospective cohort , 2017, PloS one.

[4]  M. Tanner,et al.  Cohort profile: The Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) - A prospective HIV cohort in rural Tanzania. , 2017, Swiss medical weekly.

[5]  A. Kamali,et al.  Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk , 2016, AIDS research and human retroviruses.

[6]  J. Walson,et al.  Antihelminthics in helminth‐endemic areas: effects on HIV disease progression , 2016, The Cochrane database of systematic reviews.

[7]  Mirko S. Winkler,et al.  Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis. , 2015, The Lancet. Infectious diseases.

[8]  J. Utzinger,et al.  New diagnostic tools in schistosomiasis. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[9]  K. Yirdaw,et al.  Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia , 2015, PloS one.

[10]  J. Utzinger,et al.  Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings , 2015, PLoS neglected tropical diseases.

[11]  C. King,et al.  HIV and schistosomiasis co-infection in African children. , 2014, The Lancet. Infectious diseases.

[12]  Elisa M. Tjon Kon Fat,et al.  Tools for diagnosis, monitoring and screening of Schistosoma infections utilizing lateral-flow based assays and upconverting phosphor labels , 2014, Parasitology.

[13]  P. Bretscher.  On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases , 2014, Scandinavian journal of immunology.

[14]  N. Taveira,et al.  Predictors of Attrition and Immunological Failure in HIV-1 Patients on Highly Active Antiretroviral Therapy from Different Healthcare Settings in Mozambique , 2013, PloS one.

[15]  André M Deelder,et al.  A robust dry reagent lateral flow assay for diagnosis of active schistosomiasis by detection of Schistosoma circulating anodic antigen. , 2013, Experimental parasitology.

[16]  J. H. van de Wijgert,et al.  Low Primary and Secondary HIV Drug-Resistance after 12 Months of Antiretroviral Therapy in Human Immune-Deficiency Virus Type 1 (HIV-1)-Infected Individuals from Kigali, Rwanda , 2013, PloS one.

[17]  D. Karanja,et al.  Association between CD4+ T-lymphocyte counts and fecal excretion of Schistosoma mansoni eggs in patients coinfected with S. mansoni and human immunodeficiency virus before and after initiation of antiretroviral therapy. , 2013, The American journal of tropical medicine and hygiene.

[18]  H. Bang,et al.  Schistosomiasis and Impaired Response to Antiretroviral Therapy Among HIV-Infected Patients in Tanzania , 2013, Journal of acquired immune deficiency syndromes.

[19]  K. Radcliffe,et al.  Eosinophilia: clinical significance in HIV-infected individuals , 2012, International journal of STD & AIDS.

[20]  W. Secor,et al.  The effects of schistosomiasis on HIV/AIDS infection, progression and transmission , 2012, Current opinion in HIV and AIDS.

[21]  J. Gonzalez,et al.  Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon , 2012, Journal of the International AIDS Society.

[22]  L. Chitsulo,et al.  Examining the Relationship between Urogenital Schistosomiasis and HIV Infection , 2011, PLoS neglected tropical diseases.

[23]  R. Wood,et al.  Low Rates of Nucleoside Reverse Transcriptase Inhibitor Resistance in a Well-Monitored Cohort in South Africa on Antiretroviral Therapy , 2011, Antiviral therapy.

[24]  G. Walzl,et al.  The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa , 2011, BMC infectious diseases.

[25]  B. Berkhout,et al.  Altered dynamics and differential infection profiles of lymphoid and myeloid cell subsets during acute and chronic HIV‐1 infection , 2011, Journal of leukocyte biology.

[26]  C. Menéndez,et al.  Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome in a Rural Area of Mozambique , 2011, PloS one.

[27]  Peter J. Hotez,et al.  Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden , 2009, PLoS neglected tropical diseases.

[28]  M. Egger,et al.  Mortality of Patients Lost to Follow-Up in Antiretroviral Treatment Programmes in Resource-Limited Settings: Systematic Review and Meta-Analysis , 2009, PloS one.

[29]  J. Overbaugh,et al.  Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial , 2008, AIDS.

[30]  Michael Hoelscher,et al.  Laboratory reference values for healthy adults from southern Tanzania , 2008, Tropical medicine & international health : TM & IH.

[31]  H. Tanke,et al.  Up-Converting Phosphor Technology-Based Lateral Flow Assay for Detection of Schistosoma Circulating Anodic Antigen in Serum , 2007, Journal of Clinical Microbiology.

[32]  H. Ullum,et al.  Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load. , 2005, The Journal of infectious diseases.

[33]  H. Ullum,et al.  Schistosomiasis and HIV-1 infection in rural Zimbabwe: implications of coinfection for excretion of eggs. , 2005, The Journal of infectious diseases.

[34]  A. Mocroft,et al.  Predictors of immunological failure after initial response to highly active antiretroviral therapy in HIV-1-infected adults: a EuroSIDA study. , 2004, The Journal of infectious diseases.

[35]  A. Mocroft,et al.  Starting highly active antiretroviral therapy: why, when and response to HAART. , 2004, The Journal of antimicrobial chemotherapy.

[36]  A. Deelder,et al.  Immunodiagnosis of schistosomiasis by determination of the circulating antigens CAA and CCA, in particular in individuals with recent or light infections. , 2000, Acta tropica.

[37]  B. Nahlen,et al.  Studies on schistosomiasis in western Kenya: II. Efficacy of praziquantel for treatment of schistosomiasis in persons coinfected with human immunodeficiency virus-1. , 1998, The American journal of tropical medicine and hygiene.

[38]  G. Vanham,et al.  Eosinophilia in patients infected with human immunodeficiency virus. , 1996, The Journal of infectious diseases.

[39]  M. Clerici,et al.  CD8+ lymphocyte phenotype and cytokine production in long‐term non‐progressor and in progressor patients with HIV‐1 infection , 1996, Clinical and experimental immunology.

[40]  J. Berzofsky,et al.  Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen. , 1992, Journal of immunology.

[41]  A. Deelder,et al.  Circulating anodic antigen levels in serum before and after chemotherapy with praziquantel in schistosomiasis mansoni. , 1989, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[42]  R. Steigbigel,et al.  Eosinophilia in patients infected with human immunodeficiency virus. , 1996, The Journal of infectious diseases.

[43]  A. Deelder,et al.  Quantitative diagnosis of Schistosoma infections by measurement of circulating antigens in serum and urine. , 1994, Tropical and geographical medicine.

[44]  S. Lucas,et al.  Immunological control of hepatotoxicity and parasite egg excretion in Schistosoma mansoni infections: stage specificity of the reactivity of immune serum in T-cell deprived mice. , 1981, Transactions of the Royal Society of Tropical Medicine and Hygiene.