Herpes simplex virus type 1 infections.

Topics in HIV Medicine 138 Sexually transmitted infections (STIs) are commonly underdiagnosed by HIV care practitioners. Thus, it is important to increase vigilance and recognize that STIs are often asymptomatic or have nonspecific symptoms, that their presence can increase HIV infectious-ness, and that regular testing for STIs is needed to ensure optimal treatment of HIV-infected patients. Twenty years' worth of epidemiologic data support a synergistic relationship between herpes simplex virus type 2 (HSV-2) and HIV infections. Reactiva-tion of HSV-2 increases HIV susceptibility and infectiousness and potentially accelerates HIV disease progression. Also, HIV infection increases the frequency of HSV-2 outbreaks, facilitating HSV-2 transmission. Numerous longitudinal studies that were adjusted for age and sexual behavior have shown that prevalent HSV-2 infection is associated with a statistically significant increase in the relative risk (RR) of HIV acquisition in men (RR, 2.7), women (RR, 3.1), and men who have sex with men (MSM; RR, 1.7). The risk of HIV acquisition appears to be even higher in patients with incident (recently acquired) HSV-2 infection (RR, ~6), although it is difficult to discern whether individuals acquired HSV-2 infection before or at the same time as HIV infection. In some African locales where HSV-2 prevalence is very high, mathematical modeling and epidemiologic analyses estimate that up to one-third to one-half of new HIV infections can be attributed to HSV-2 infection. Biological plausibility for increased HIV susceptibility comes from various lines of evidence. These include studies showing that HSV-2 causes mac-roscopic and microscopic ulcerations and that HSV-2 reactivation is quite frequent. Studies of HIV-seronegative persons in which patient-obtained genital swabs were tested by HSV polymerase chain reaction show that reactivation occurs on 20% of days and even more frequently if HSV shedding is evaluated more than once daily (Mark et al, J Infect Dis, 2008). Also, HSV-2-infected women who were not necessarily shedding virus had increased populations of HIV target cells, specifically immature dendritic cells and cervical CD4+ T cells expressing CC chemokine receptor 5 (CCR5) (Rebbapragada et al, AIDS, 2007). Such data provided the rationale for investigating whether suppression of HSV-2 could reduce acquisition of HIV. In a placebo-controlled study in 821 HSV-2-seropositive, HIV-seronega-tive Tanzanian women at high risk of HIV infection—a study in which the drop-out rate was high, adherence was modest, and clinic visits occurred only quarterly—twice-daily acyclovir 400 mg showed no effect in preventing HIV acquisition (Watson-Jones et al, N Engl J Med, 2008). …