Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

Lankowski, Alexander; Tsai, Alexander C.; Kanyesigye, Michael; Bwana, Mwebesa; Haberer, Jessica; Wenger, Megan; Martin, Jeffrey N.; Bangsberg, David R.; Hunt, Peter W.; Siedner, Mark J.

doi:10.1371/journal.pntd.0003036

Cited by 12 publications

(13 citation statements)

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“…the mean age of that cohort). Sub‐Saharan Africa is an endemic environment for intestinal parasites, which usually go untreated except in deworming campaigns . The lower CD4 T‐cell levels in the Israeli cohort compared with the Mekelle cohort do not support the hypothesis that environmental and nutritional factors account for the difference in the frequency of HIV‐positive ECs between the two cohorts.…”

Section: Discussionmentioning

confidence: 86%

“…Additionally, the chronic parasitic burden in the Ethiopian setting has been suggested to be a factor associated with immune dysregulation and activation [14]. Deworming seems to lead to decreased immune regulation and increased immune responsiveness [15], although its effect in HIV/AIDS has been a matter of controversy [16]. It is conceivable that a reduction in overall immune activation caused by the modified nutrition and environment following immigration may contribute to the maintenance of the EC state and may thus explain our findings of a higher prevalence of EC among HIV-positive immigrants in Israel.…”

Section: Discussionmentioning

confidence: 99%

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Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel

et al. 2018

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Objectives HIV elite controllers (ECs) are a unique subgroup of HIV-positive patients who are long-term virologically suppressed in the absence of antiretroviral treatment (ART). The prevalence of this subgroup is estimated to be < 1%. Various cohorts of ECs have been described in developed countries, most of which have been demographically heterogeneous. The aim of this study was to identify ECs in two large African cohorts and to estimate their prevalence in a relatively genetically homogenous population. Methods We screened two cohorts of HIV-positive Ethiopian patients. The first cohort resided in Mekelle, Ethiopia. The second was comprised of HIV-positive Ethiopian immigrants in Israel. In the Mekelle cohort, ART-naïve subjects with stable CD4 counts were prospectively screened using two measurements of viral load 6 months apart. Subjects were defined as ECs when both measurements were undetectable. In the Israeli cohort, subjects with consistently undetectable viral loads (mean of 17 viral load measurements/patient) and stable CD4 count > 500 cells/µL were defined as ECs. Results In the Mekelle cohort, 16 of 9515 patients (0.16%) fitted the definition of EC, whereas seven of 1160 (0.6%) in the Israeli cohort were identified as ECs (P = 0.011). Conclusions This is the first large-scale screening for HIV-positive ECs to be performed in entirely African cohorts. The overall prevalence of ECs is within the range of that previously described in developing countries. The significant difference in prevalence between the two cohorts of similar genetic background is probably a consequence of selection bias but warrants further investigation into possible environmental factors which may underlie the EC state.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel

et al. 2018

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“…[14, 15] In Uganda, Lankowski et al . did not find any significant beneficial effects of deworming in their overall study population.…”

Section: Discussionmentioning

confidence: 99%

Hookworm infection is associated with decreased CD4+ T cell counts in HIV-infected adult Ugandans

et al. 2017

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Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method. This cohort study enrolled HIV-infected Ugandans from August-September 2013 in Mbale, Uganda and collected stool and blood samples at enrollment. Real-time PCR quantified stool: Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica, and Giardia intestinalis infection. Generalized linear models assessed relationships between parasitic infection and clinical or demographic data. 35% of participants (71/202) tested positive for ≥1 helminth, mainly N. americanus (55/199, 28%), and 4.5% (9/202) were infected with ≥2 stool parasites. Participants with hookworm infection had lower average CD4+ cell counts (-94 cells/mcL, 95%CI: -141, -48 cells/mcL; p<0.001) after adjustment for sex, CD4+ nadir at clinic entry, and time on ART. The high prevalence of parasitic infection and correlation with decreased CD4+ concentrations highlight the need to re-examine the effects of invasive helminth co-infection in rural, HIV-infected populations in the era of widely available ART. Elucidating the relationship between hookworm infection and immune recovery could provide opportunities for health optimization, e.g. integrated deworming, in these vulnerable populations.

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“…Several studies have noted delays in HIV disease progression following deworming (Brown 2005; Ivan 2015; Lankowski 2014; Mulu 2013; Muok 2013; Wolday 2002 ), while others have reported no association (Brown 2004; Elliott 2003; Hosseinipour 2007; Kleppa 2014; Lawn 2000; Modjarrad 2005). In the previous version of this systematic review we found some evidence from randomized controlled trials of short term benefits with deworming but also the need for further larger studies (Walson 2009).…”

Section: Introductionmentioning

confidence: 99%

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

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Sinclair

et al. 2016

Cochrane Database of Systematic Reviews

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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...

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Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

Cited by 12 publications

References 57 publications

Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel

Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel

Hookworm infection is associated with decreased CD4+ T cell counts in HIV-infected adult Ugandans

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

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