The role of coinfections in HIV epidemic trajectory and positive prevention: a systematic review and meta-analysis

Abstract

Objectives: Recurrent or persistent coinfections may increase HIV viral load and, consequently, risk of HIV transmission, thus increasing HIV incidence. We evaluated the association between malaria, herpes simplex virus type 2 (HSV-2) and tuberculosis (TB) coinfections and their treatment on HIV viral load.

Design: Systematic review and meta-analysis of the association of malaria, HSV-2 and TB coinfections and their treatment with HIV viral load.

Methods: PubMed and Embase databases were searched to 10 February 2010 for studies in adults that reported HIV plasma and/or genital viral load by coinfection status or treatment. Meta-analyses were conducted using random-effects models.

Results: Forty-five eligible articles were identified (six malaria, 20 HSV-2 and 19 TB). There was strong evidence of increased HIV viral load with acute malaria [0.67 log(10) copies/ml, 95% confidence interval (CI) 0.15-1.19] and decreased viral load following treatment (-0.37 log(10) copies/ml, 95% CI -0.70 to -0.04). Similarly, HSV-2 infection was associated with increased HIV viral load (0.18 log(10) copies/ml, 95% CI 0.01-0.34), which decreased with HSV suppressive therapy (-0.28 log(10) copies/ml, 95% CI -0.36 to -0.19). Active TB was associated with increased HIV viral load (0.40 log(10) copies/ml, 95% CI 0.13-0.67), but there was no association between TB treatment and viral load reduction (log(10) copies/ml -0.02, 95% CI -0.19 to 0.15).

Conclusion: Coinfections may increase HIV viral load in populations where they are prevalent, thereby facilitating HIV transmission. These effects may be reversed with treatment. However, to limit HIV trajectory and optimize positive prevention for HIV-infected individuals pre-antiretroviral therapy, we must better understand the mechanisms responsible for augmented viral load and the magnitude of viral load reduction required, and retune treatment regimens accordingly.

Fig. 1. Systematic review flowhart

¹Malaria: pregnancy [55], no VL data [51], review/comment [16], subjects on ART/malaria prophylaxis [4], malaria and mortality/disease progression (not VL) [4], biological mechanism of interaction [3], mathematical model [3], Immunilogy [2], children [1], no data on CD4 count [1]. ²HSV-2: no VL data [55], review/comment [25], identified in previous reivew of HIV acquisition [20], pregnancy [10], HSV-2 is outcome [7], biological mechanism of interaction [5], mathematical model [5], HIV acquisition but with no adjustment for other risk factors [3], subjects on ART/other intervention [3], HSV-2 and mortality/disease progression (not VL) [3], baseline data of RCT [1], not HSV-2 [1]. ³TB: not VL data [63], review/comment [43], risk of TB acquisition [17], subjects on ART/other treatment [16], biological mechniasm of interaction [14], genetics [9], no data on CD4 count [9], Immunology [8], TB and mortaligy/disease progression (not VL) [4], pregnancy [3], mathematical model [2], control group hadsuspected TB [1].

Fig. 2