Association of HIV infection with extrapulmonary tuberculosis: a systematic review

Abstract

Purpose: HIV/AIDS is a known risk factor for the development of pulmonary tuberculosis (PTB). However, the association is less clear between HIV and extrapulmonary tuberculosis (EPTB). We conducted a systematic review to determine the association between HIV and EPTB.

Methods: We searched the electronic databases Medline, Embase, and relevant conference literature using defined search terms for EPTB and HIV. Only publications in English and only studies reporting adjusted estimates were included, while our search criteria did not include restriction by age or geographic location of study participants. Qualitative and quantitative analyses (including I ² test for heterogeneity) were performed.

Results: Sixteen studies (15 cross-sectional and 1 case-control) conducted from 1984 to 2016 were included in the final analyses after screening 5163 articles and conference abstracts. Our qualitative analysis showed heterogeneity in study design and study population characteristics along with a medium/high risk of bias in the majority of studies. While most of the individual studies showed increased odds of EPTB compared with PTB among HIV-infected individuals, we did not provide an overall pooled estimate, as the I ² value was high at 93% for the cross-sectional studies.

Conclusions: While an association between HIV and EPTB is observed in most individual studies, the high heterogeneity and risk of bias in these studies highlight the need for further well-designed prospective cohort studies to assess the true risk of EPTB in the HIV-infected patient population.

Keywords: EPTB; HIV; Pulmonary TB; Systematic review; TB.

Figure 1. PRISMA diagram of search strategy for systematic review

Figure 1 Legend: Flow chart showing the search strategy utilized in this study. Articles from PubMed and EMBASE were screened for full-text review. The most common reasons for removing articles included: the absence of effect estimates; study design (e.g., case studies or review articles); languages other than English; and the use of unadjusted estimates. The remaining 16 citations are the basis of the articles used in this systematic review. Two separate searches were performed for this study. The first search was performed on February 2014 and the figure shows the number of articles screened and full-text read resulting in final selection of 10 articles. The second search was performed on August 2016 as an update since the first search. For this search, 250 articles were screened and 9 articles went full-text review to select 6 new articles.

Figure 2. Forest Plot of the association of HIV with EPTB

Figure 2 Legend: Forest plot showing the association of HIV with EPTB (relative to PTB or no EPTB [26]). The x-axis shows the effect estimate (ES) and 95% confidence intervals (CI). The weight, based on sample size, is shown along with the study design, I-squared value, study year and author. Overall effect estimates are not shown due to the high degree of heterogeneity between studies.