title: Antihelminthics in helminth-endemic areas: effects on HIV disease progression.
abstract: BACKGROUND
  Helminth 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.
  
  
  OBJECTIVE
  To evaluate the effects of deworming drugs (antihelminthic therapy) on markers of HIV disease progression, anaemia, and adverse events in children and adults.
  
  
  METHODS
  In this review update, we searched online for published and unpublished studies in the Cochrane Library, MEDLINE, EMBASE, CENTRAL, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICRTP),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.
  
  
  METHODS
  We searched for randomized controlled trials (RCTs) that compared antihelminthic drugs with placebo or no intervention in HIV-positive people.
  
  
  METHODS
  Two 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.
  
  
  RESULTS
  Eight 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 load (difference in mean change 0.01 log10 viral RNA, 95% CI: -0.03 to -0.05; one trial, 917 participants, moderate quality evidence), and little or no effect on mean CD4+ count (difference in mean change 2.60 CD4+ cells/µL, 95% CI -10.15 to 15.35; P = 0.7; one trial, 917 participants, low quality evidence). Antihelminthics for people with confirmed helminth infectionsTreating confirmed helminth infections in HIV-positive adults may have a small suppressive effect on mean viral load at six to 12 weeks following deworming (difference in mean change -0.13 log10 viral RNA, 95% CI -0.26 to -0.00; P = 0.04; four trials, 445 participants, low quality evidence). However, this finding is strongly influenced by a single study of praziquantel treatment for schistosomiasis. There may also be a small favourable effect on mean CD4+ cell count at 12 weeks after deworming in HIV-positive populations with confirmed helminth infections (difference in mean change 37.86 CD4+ cells/µL, 95% CI 7.36 to 68.35; P = 0.01; three trials, 358 participants, low quality evidence). Adverse events and mortality There is no indication that antihelminthic drugs impart additional risks in HIV-positive populations. However, adverse events were not well reported (very low quality evidence) and trials were underpowered to evaluate effects on mortality (low quality evidence).
  
  
  CONCLUSIONS
  There is low quality evidence that treating confirmed helminth infections in HIV-positive adults may have small, short-term favourable effects on markers of HIV disease progression. Further studies are required to confirm this finding. Current evidence suggests that deworming with antihelminthics is not harmful, and this is reassuring for the routine treatment of confirmed or suspected helminth infections in people living with HIV in co-endemic areas.Further long-term studies are required to make confident conclusions regarding the impact of presumptively deworming all HIV-positive individuals irrespective of helminth infection status, as the only long-term trial to date did not demonstrate an effect.
authors.affiliation: Department of Global Health, University of Washington, Seattle, Washington, USA.
authors.forename: Arianna Rubin
authors.initials: AR
authors.lastname: Means
authors.forename: Paul
authors.initials: P
authors.lastname: Burns
authors.forename: David
authors.initials: D
authors.lastname: Sinclair
authors.forename: Judd L
authors.initials: JL
authors.lastname: Walson
mesh_terms: D000328:Adult; D000871:Anthelmintics / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D019353:Endemic Diseases; D015658:HIV Infections / Q000276:immunology / Q000469:parasitology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006295:Health Resources; D006373:Helminthiasis / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D011204:Poverty Areas; D012367:RNA, Viral / Q000032:analysis; D016032:Randomized Controlled Trials as Topic; D019562:Viral Load
chemical_list: D000871:Anthelmintics; D012367:RNA, Viral