Antihelminthics in helminth-endemic areas: effects on HIV disease progression

Abstract

BackgroundHelminth infections, such as soil-transmitted helminths, schistosomiasis, onchocerciasis, and lymphatic filariasis, are prevalent in many countries where human immunodeficiency virus (HIV) infection is also common. There is some evidence from observational studies that HIV and helminth co-infection may be associated with higher viral load and lower CD4+ cell counts. Treatment of helminth infections with antihelminthics (deworming drugs) may have benefits for people living with HIV beyond simply clearance of worm infections.This is an update of a Cochrane Review published in 2009 and we have expanded it to include outcomes of anaemia and adverse events.ObjectivesTo evaluate the effects of deworming drugs (antihelminthic therapy) on markers of HIV disease progression, anaemia, and adverse events in children and adults.Search methodsIn this review update, we searched online for published and unpublished studies in the Cochrane Library, MEDLINE, EMBASE, CENTRAL, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICRTP), ClinicalTrials.gov, and the WHO Global Health Library up to 29 September 2015. We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted the authors of included studies.Selection criteriaWe searched for randomized controlled trials (RCTs) that compared antihelminthic drugs with placebo or no intervention in HIV-positive people.Data collection and analysisTwo review authors independently extracted data and assessed trials for eligibility and risk of bias. The primary outcomes were changes in HIV viral load and CD4+ cell count, and secondary outcomes were anaemia, iron deficiency, adverse events, and mortality events. We compared the effects of deworming using mean differences, risk ratios (RR), and 95% confidence intervals (CIs). We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Main resultsEight trials met the inclusion criteria of this review, enrolling a total of 1612 participants. Three trials evaluated the effect of providing antihelminthics to all adults with HIV without knowledge of their helminth infection status, and five trials evaluated the effects of providing deworming drugs to HIV-positive individuals with confirmed helminth infections. Seven trials were conducted in sub-Saharan Africa and one in Thailand.Antihelminthics for people with unknown helminth infection statusProviding antihelminthics (albendazole and praziquantel together or separately) to HIV-positive adults with unknown helminth infection status may have a small suppressive effect on mean viral load at six weeks but the 95% CI includes the possibility of no effect (difference in mean change −0.14 log10 viral RNA/mL, 95% CI −0.35 to 0.07, P = 0.19; one trial, 166 participants, low quality evidence).Repeated dosing with deworming drugs over two years (albendazole every three months plus annual praziquantel), probably has little or no effect on mean viral loa...

Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: A nested case-control study

“…This finding of increased HIV-1 RNA viral load at seroconversion is supported by studies from humans and mice showing that schistosome-induced immune alterations may impair the host’s ability to control viral replication. It is also supported by a recent Cochrane review suggesting that treatment of helminth infections in HIV-helminth co-infected individuals may decrease the HIV-1 RNA viral load [ 42 ]. Mouse models demonstrate that schistosome infections shift host immunity away from antiviral cytolytic T-helper (Th)-1 immune responses and towards a Th2-predominant state, thereby prompting reactivation of latent viruses [ 43 , 44 ].…”

Combined effectiveness of anthelmintic chemotherapy and WASH among HIV-infected adults

“…Finally, because the study was conducted in HIV-infected adults, the generalizability of our findings may be limited. However, there is some evidence that HIV infected adults may benefit from deworming and the potential additive role of WASH in this population warrants further investigation [ 42 ]. Lastly, if helminth acquired immunities are age-dependent, one might expect these protective resources to have more pronounced influences in younger populations.…”

Soil-transmitted helminth infections

“…162 Indeed, a recent review argues that the 'hygiene hypothesis' is not valid with regard to helminth infections, and suggests that research should rather prioritise identifying potential helminth-derived therapeutic molecules. 163 Finally, data suggest that deworming may have beneficial effects on co-infections such as HIV, 164,165 and further research is needed to determine the impact of anthelmintic treatment on malaria. 166,167 OUTSTANDING RESEARCH One of the principal bottlenecks for adequate individual diagnosis and management, as well as public health control of STH, has been insufficient investment in research and development of diagnostic tools and treatment options.…”