The Effect of STI Co-Infections on HIV Viral Load
The Effect of STI Co-Infections on HIV Viral Load
A large body of evidence suggests that antiretroviral therapy (ART), particularly with newer treatment regimens, markedly reduces the risk of sexual transmission of HIV. Recent systematic reviews have estimated that ART causes a more than ten-fold reduction in the incidence rate within discordant couples, to less than 0.5 per 100 person-years.
These sharp reductions have inspired the idea of antiretroviral treatment as prevention—aggressive programs to identify and treat HIV-positive individuals could substantially reduce HIV incidence at the population level, by reducing the infectiousness of HIV-infected individuals. However, increased infectiousness when treated individuals are co-infected with one or more other sexually transmitted infections (STIs) could potentially undercut the effectiveness of treatment as prevention programs. Concern with the effects of co-infection on HIV transmission is exemplified in the 2008 "Swiss Statement," which argues that HIV sexual transmission risk is of no concern within stable discordant relationships in which: an HIV-positive partner is adhering to treatment under the care of a physician; the viral load has been suppressed for at least six months; and no other STIs are infecting the HIV-positive partner.
Although the biological mechanisms underlying this increased risk are not fully understood, many STIs have been associated with higher risks of both HIV acquisition and sexual transmission. Increased HIV transmission may be underpinned by higher HIV viral load resulting from larger concentration of HIV-infected immune cells in genital secretions induced by an inflammatory response and/or additional pathways caused by genital ulcers. Similarly, inflammatory STIs, by recruiting immune cells, may provide additional targets for HIV virions, increasing HIV acquisition risk. Ulcerative STIs may present additional entry points for HIV infection.
Studies of HIV-STI interactions have been conducted mostly on individuals not receiving ART. Less is known about the impact of STI co-infections on HIV shedding from treated individuals. STI prevalence is high among HIV-infected individuals and the proportion of these individuals on ART is quickly rising. Thus, any potential increased HIV infectiousness due to STI co-infections among treated individuals could have important epidemiological consequences as treatment as prevention becomes more widespread.
Disentangling the many interacting factors at play is challenging: many STIs are suspected of affecting HIV shedding and it remains unclear whether how these effects interact in people with more than one such infection; the viral load response to ART is regimen- and gender-specific; numerous (not necessarily consistent) methods are used to sample and quantify HIV viral load; viral load measurements can vary between anatomical sites within an infected individual; and HIV viral loads exhibit substantial temporal variation. When considering transmission events in discordant couples, isolating the effect of STI co-infections is challenging because concomitance of STI infections in both partners (that could affect both HIV susceptibility and infectiousness) and HIV transmission are often not practical to ascertain.
Here, we conduct a systematic review and meta-analysis of the available evidence to assess whether STI co-infections affect the risk of HIV transmission from individuals on ART. We searched for studies that estimated transmission directly, and also for studies that measured viral load, which we intended to use as a proxy for transmission if the direct evidence was insufficient.
Background
A large body of evidence suggests that antiretroviral therapy (ART), particularly with newer treatment regimens, markedly reduces the risk of sexual transmission of HIV. Recent systematic reviews have estimated that ART causes a more than ten-fold reduction in the incidence rate within discordant couples, to less than 0.5 per 100 person-years.
These sharp reductions have inspired the idea of antiretroviral treatment as prevention—aggressive programs to identify and treat HIV-positive individuals could substantially reduce HIV incidence at the population level, by reducing the infectiousness of HIV-infected individuals. However, increased infectiousness when treated individuals are co-infected with one or more other sexually transmitted infections (STIs) could potentially undercut the effectiveness of treatment as prevention programs. Concern with the effects of co-infection on HIV transmission is exemplified in the 2008 "Swiss Statement," which argues that HIV sexual transmission risk is of no concern within stable discordant relationships in which: an HIV-positive partner is adhering to treatment under the care of a physician; the viral load has been suppressed for at least six months; and no other STIs are infecting the HIV-positive partner.
Although the biological mechanisms underlying this increased risk are not fully understood, many STIs have been associated with higher risks of both HIV acquisition and sexual transmission. Increased HIV transmission may be underpinned by higher HIV viral load resulting from larger concentration of HIV-infected immune cells in genital secretions induced by an inflammatory response and/or additional pathways caused by genital ulcers. Similarly, inflammatory STIs, by recruiting immune cells, may provide additional targets for HIV virions, increasing HIV acquisition risk. Ulcerative STIs may present additional entry points for HIV infection.
Studies of HIV-STI interactions have been conducted mostly on individuals not receiving ART. Less is known about the impact of STI co-infections on HIV shedding from treated individuals. STI prevalence is high among HIV-infected individuals and the proportion of these individuals on ART is quickly rising. Thus, any potential increased HIV infectiousness due to STI co-infections among treated individuals could have important epidemiological consequences as treatment as prevention becomes more widespread.
Disentangling the many interacting factors at play is challenging: many STIs are suspected of affecting HIV shedding and it remains unclear whether how these effects interact in people with more than one such infection; the viral load response to ART is regimen- and gender-specific; numerous (not necessarily consistent) methods are used to sample and quantify HIV viral load; viral load measurements can vary between anatomical sites within an infected individual; and HIV viral loads exhibit substantial temporal variation. When considering transmission events in discordant couples, isolating the effect of STI co-infections is challenging because concomitance of STI infections in both partners (that could affect both HIV susceptibility and infectiousness) and HIV transmission are often not practical to ascertain.
Here, we conduct a systematic review and meta-analysis of the available evidence to assess whether STI co-infections affect the risk of HIV transmission from individuals on ART. We searched for studies that estimated transmission directly, and also for studies that measured viral load, which we intended to use as a proxy for transmission if the direct evidence was insufficient.
