Review
Effect of treating co-infections on HIV-1 viral load: a systematic review

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Summary

Co-infections contribute to HIV-related pathogenesis and often increase viral load in HIV-infected people. We did a systematic review to assess the effect of treating key co-infections on plasma HIV-1-RNA concentrations in low-income countries. We identified 18 eligible studies for review: two on tuberculosis, two on malaria, six on helminths, and eight on sexually transmitted infections, excluding untreatable or non-pathogenic infections. Standardised mean plasma viral load decreased after the treatment of co-infecting pathogens in all 18 studies. The standardised mean HIV viral-load difference ranged from −0·04 log10 copies per mL (95% CI −0·24 to 0·16) after syphilis treatment to −3·47 log10 copies per mL (95% CI −3·78 to −3·16) after tuberculosis treatment. Of 14 studies with variance data available, 12 reported significant HIV viral-load differences before and after treatment. Although many of the viral-load reductions were 1·0 log10 copies per mL or less, even small changes in plasma HIV-RNA concentrations have been shown to slow HIV progression and could translate into population-level benefits in lowering HIV transmission risk.

Introduction

Sustainable and affordable therapeutic and preventive strategies for HIV and AIDS in settings with limited health-care resources represent a formidable public health challenge. Despite widespread implementation of antiretroviral therapy programmes, medications were inaccessible or not yet indicated for 71% of the world's HIV-infected people at the end of 2008.1 Antiretroviral therapy improves HIV prognosis and reduces infectiousness through the reduction of plasma and genital viral load. However, treatment requires a life-long, daily regimen supported by periodic laboratory tests to monitor the efficacy and toxicity of treatment. Furthermore, patients without opportunistic infections and with higher CD4 cell counts (ie, >350×106/L) might be advised to defer antiretroviral therapy in settings with limited health-care resources. Thus, there remains a compelling imperative to prevent HIV transmission and to improve the prognosis of individuals infected with HIV in settings where antiretroviral therapy is either not yet available or indicated.

In the 1980s, before the era of antiretroviral therapy, much attention was given to HIV co-infections and their effect on host immunity.2 In-vitro data early in the HIV epidemic showed that infections endemic to low-income countries upregulate HIV transcription and robustly activate cellular immunity.3, 4, 5, 6 Subsequent human studies have suggested that treatment of co-infections could translate into small HIV viral-load reductions.7, 8, 9, 10, 11, 12 A greater focus on co-infections among patients not yet on antiretroviral therapy is warranted for several reasons: there is a high burden of co-infections in HIV-endemic zones; many co-infections non-specifically activate host immunity;6, 13, 14, 15, 16, 17 some organisms can directly facilitate HIV replication;18, 19 and small HIV viral-load reductions could translate into benefits in disrupting viral transmission and improving AIDS-free survival.20

Despite increasing evidence for its salience to HIV outcomes, the effect of co-infection clearance on HIV viral load has not yet been systematically reviewed or quantitatively summarised. We therefore did a systematic review of published studies that assess the effect of treating co-infections that are common in low-income countries on plasma concentrations of HIV-1 RNA, a primary surrogate for HIV transmission risk and disease progression.

Section snippets

Search strategy

We searched PubMed, Medline, AEGIS, Embase, and LILACS databases for studies published between Jan 1, 1987, and April 1, 2010, and available conference proceedings from the American Society of Tropical Medicine and Hygiene (2004–09), International AIDS Society (1987–2009), and the Conference on Retroviruses and Opportunistic Infections (1997–2010). In our search, we used permutations of key terms including “HIV”, “RNA”, “viral load”, “co-infection”, and “treatment”, as well as those specific

Results

The search yielded 3130 articles, of which 100 were relevant for full review and 14 were eligible for inclusion.6, 7, 10, 11, 12, 24, 25, 26, 27, 28, 29, 30, 31, 32 Four additional studies were identified by cross-referencing bibliographies of all potentially relevant articles or following up meeting reports.33, 34, 35, 36 Of the 18 eligible studies, ten were observational6, 10, 11, 12, 24, 28, 29, 30, 32, 34 and eight were randomised controlled trials (figure 1).7, 25, 26, 27, 31, 33, 35, 36

Discussion

Our systematic review suggests that treatment of the major co-infections of the world's HIV-infected populations would be likely to reduce HIV viral load at an individual and population level. Although most studies eligible for this Review showed significant reductions in viral load, several studies failed to show a clinically significant change that exceeds the inherent 0·2–0·3 log10 copies per mL fluctuation of viral-load measures.37, 38, 39 Nevertheless, our analysis showed a viral-load

Conclusions

Despite compelling evidence from immunological studies that co-infections activate host immunity, which in turn enhances HIV replication, evidence that treatment of or recovery from co-infection reduces HIV viral load has been elusive. Results from studies that have assessed changes in HIV-RNA concentrations after successful treatment or suppression of a co-infection varied in magnitude from an increase of 0·04 log10 copies per mL to a reduction of 3·47 log10 copies per mL. Interpretation of

Search strategy and selection criteria

These are described in detail in the Methods section.

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