Research Article: Treatment of Helminth Co-Infection in Individuals with HIV-1: A Systematic Review of the Literature

Date Published: December 19, 2007

Publisher: Public Library of Science

Author(s): Judd L. Walson, Grace John-Stewart, Simon Brooker

Abstract: Background and ObjectivesThe HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings. It is important to determine if other prevalent infections affect the progression of HIV-1 in co-infected individuals in these settings. Some observational studies suggest that helminth infection may adversely affect HIV-1 progression. We sought to evaluate existing evidence on whether treatment of helminth infection impacts HIV-1 progression.Review MethodsThis review was conducted using the HIV/AIDS Cochrane Review Group (CRG) search strategy and guidelines. Published and unpublished studies were obtained from The Cochrane Library (Issue 3, 2006), MEDLINE (November 2006), EMBASE (November 2006), CENTRAL (July 2006), and AIDSEARCH (August 2006). Databases listing conference abstracts and scanned reference lists were searched, and authors of included studies were contacted. Data regarding changes in CD4 count, HIV-1 RNA levels, clinical staging and/or mortality were extracted and compared between helminth-treated and helminth-untreated or helminth-uninfected individuals.ResultsOf 6,384 abstracts identified, 15 met criteria for potential inclusion, of which 5 were eligible for inclusion. In the single randomized controlled trial (RCT) identified, HIV-1 and schistosomiasis co-infected individuals receiving treatment for schistosomiasis had a significantly lower change in plasma HIV-1 RNA over three months (−0.001 log10 copies/mL) compared to those receiving no treatment (+0.21 log10 copies/mL), (p = 0.03). Four observational studies met inclusion criteria, and all of these suggested a possible beneficial effect of helminth eradication on plasma HIV-1 RNA levels when compared to plasma HIV-1 RNA changes prior to helminth treatment or to helminth-uninfected or persistently helminth-infected individuals. The follow-up duration in these studies ranged from three to six months. The reported magnitude of effect on HIV-1 RNA was variable, ranging from 0.07–1.05 log10 copies/mL. None of the included studies showed a significant benefit of helminth treatment on CD4 decline, clinical staging, or mortality.ConclusionThere are insufficient data available to determine the potential benefit of helminth eradication in HIV-1 and helminth co-infected adults. Data from a single RCT and multiple observational studies suggest possible benefit in reducing plasma viral load. The impact of de-worming on markers of HIV-1 progression should be addressed in larger randomized studies evaluating species-specific effects and with a sufficient duration of follow-up to document potential differences on clinical outcomes and CD4 decline.

Partial Text: Many individuals living in areas of the world hardest hit by the HIV-1 epidemic are also infected with other common pathogens. These infections may have detrimental effects on the host’s ability to control the HIV-1 virus [1]. Some studies have suggested that these infections may result in a more rapid progression of HIV-1 disease [2]. Co-infection with other pathogens may lead to a more rapid destruction of the host immune system and potentially to earlier progression of HIV-1. Chronic helminth infection may suppress immune responses directed against HIV-1 and concurrent immune activation may directly lead to more rapid loss of CD4 cells in HIV-1 infected individuals [3].

We developed a protocol for this review for inclusion in the Cochrane Database of Systematic Reviews [17]. We included randomized or quasi-randomized controlled trials assessing the association between helminth co-infection and HIV-1 disease progression. We pre-specified that should data from clinical trials be insufficient, data from observational studies (e.g. cohort, case-control and cross-sectional studies) would be considered for inclusion in this review according to the HIV/AIDS CRG policy. Both interventional clinical trials as well as observational case control and cohort studies of HIV-1 and helminth co-infected individuals were included. Studies evaluating the effect of anti-helminthic therapy on HIV-1 progression were identified. Anti-helminthic therapy was defined as any intervention approved for use in the eradication of helminth infection in humans. This included the benzimidazoles, ivermectin, praziquantel, diethylcarbamazine, bithionol, oxamniquine, pyrantel and nitazoxanide. Control groups included placebo, no treatment, or helminth uninfected individuals. Studies evaluating changes in CD4 counts and/or HIV-1 viral load before and after anti-helminthic therapy were also included. We included studies performed in general or specific populations, in both hospitals and/or clinics, in any country and published in any language. Ecological studies were excluded. The full text of the search strategy employed has been published previously [17]. The search was conducted by two reviewers (JW and GJS). There were no disagreements in applying the inclusion criteria for selected studies.

After an expanded search strategy was employed, we identified 6,384 citations. From this list, we identified 15 potentially relevant studies, of which 5 were determined to be eligible for this review, including one randomized controlled trial and four observational studies (Figure 1). The characteristics of the included studies are presented in Table 2. All of the included studies were conducted in Africa and included HIV-1 infected individuals who were treated for a variety of different helminth infections. Four of the five studies noted that none of the participants were on antiretroviral medication while in one study [13], data on antiretroviral therapy was not provided. In the observational studies, changes in HIV-1 RNA or CD4 were compared between helminth-treated individuals and helminth uninfected controls, or controls in the period prior to helminth treatment. Three studies also compared changes in HIV-1 RNA or CD4 between treated individuals who cleared their helminth infection at follow-up and individuals who remained infected at follow-up. Unpublished data was requested from the authors of the included observational studies and included in this analysis from three of included observational studies [11],[13],[14].

It has been suggested that de-worming is unlikely to have an effect on HIV-1 progression in co-infected individuals [22]. However, to date there has been only one randomized controlled trial evaluating the potential benefit of treating helminth co-infection in HIV-1 infected individuals which was limited to evaluation of schistosomiasis co-infection. The results of our systematic review including the single randomized clinical trial and four observational studies demonstrate that there are insufficient data regarding the potential impact of de-worming on HIV-1 progression in co-infected individuals.



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