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Mechanisms by which co-infections modify HIV-1 transmission

Women with HIV-1 are frequently co-infected with other pathogens that may influence transmission of HIV-1. Bacterial, helminth, and viral infections are prevalent in settings with high HIV-1 prevalence and may be associated with immune activation, increased HIV-1 replication and genital shedding. Discerning the contribution of co-infections to HIV-1 transmission is difficult because co-infections are more prevalent with advanced HIV-1, a scenario in which transmission is concurrently elevated due to increased systemic HIV-1 burden.

Maternal plasma HIV-1 RNA level is a key determinant of vertical HIV-1 transmission. In addition, mucosal HIV-1 RNA levels in maternal secretions to which the infant is exposed (genital secretions and breastmilk) correlate with transmission risk, independent of plasma HIV-1 levels. Co-infections that cause local inflammation (STDs, mastitis) may increase local mucosal HIV-1 RNA and increase transmissibility of HIV-1. It is plausible that co-infections may contribute to some loss of efficacy of HAART regimens if local HIV-1 shedding occurs despite systemic suppression of virus. In a study with frequent serial sampling of women on HAART, episodic detection of breastmilk HIV-1 RNA occurred despite adherence suggesting local inflammation.

To date, published studies have noted associations between HSV-2, helminth, and TB infections and mother-to-child transmission of HIV-1. Of these, the evidence base is strongest for HSV-2, which has been associated with increased systemic and genital HIV-1 shedding and mother-to-child transmission of HIV-1. Decreased systemic and genital HIV-1 RNA has also been demonstrated following anti-HSV-2 treatment (valacyclovir). There is more limited evidence for helminth and TB infections, in which single studies for each have noted increased risk of vertical transmission among mothers with the co-infection. CMV co-infection is almost universally present in HIV-1 infected women and CMV co-infection is associated with disease progression in infant HIV-1 infection.

The mechanisms by which co-infections exert their effects on infant HIV-1 acquisition and progression are likely to differ. Sexually transmitted infections, in particular HSV-2, are likely to increase transmission via increases in genital HIV-1. Bacterial, helminth, CMV, or TB infections may increase immune activation and systemic HIV-1 replication, which in turn may increase infectivity. A comprehensive approach to maternal care, including management of co-infections will be useful to minimize HIV-1 transmission, morbidity, and progression in infants born to HIV-1 infected women.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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John-Stewart, G.C. Mechanisms by which co-infections modify HIV-1 transmission. Retrovirology 5 (Suppl 1), L4 (2008).

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