Celum C, Wald A, Hughes J, Sanchez J, Reid S, Delany-Moretlwe S et al.Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet 371:2109-2119

Department of Global Health, University of Washington, Seattle, WA, USA.
The Lancet (Impact Factor: 45.22). 07/2008; 371(9630):2109-19. DOI: 10.1016/S0140-6736(08)60920-4
Source: PubMed

ABSTRACT Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition.
We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with, number NCT00076232.
3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1.16 [95% CI 0.83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0.53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). We recorded no serious events related to the study drug.
Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.

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Available from: Stewart E Reid, Mar 22, 2014
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    • "Subsequently, the latent virus reactivates intermittently resulting in recurrent disease (Miller et al., 1998; Stanberry et al., 2000). In addition, genital herpes is linked to an increased susceptibility to sexually acquiring and transmitting human immunodeficiency virus (HIV; Freeman et al., 2006; Kapiga et al., 2007), which is not markedly reduced by HSV antiviral therapy (Celum et al., 2008; Watson-Jones et al., 2008). A vaccine would provide a more effective means of preventing or limiting infection, and would greatly relieve the social and economic burden of HSV-2 infection. "
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    ABSTRACT: Genital herpes is an intractable disease caused mainly by herpes simplex virus (HSV) type 2 (HSV-2), and is a major concern in public health. A previous infection with HSV type 1 (HSV-1) enhances protection against primary HSV-2 infection to some extent. In this study, we evaluated the ability of HF10, a naturally occurring replication-competent HSV-1 mutant, to protect against genital infection in mice caused by HSV-2. Subcutaneous inoculation of HF10-immunized mice against lethal infection by HSV-2, and attenuated the development of genital ulcer diseases. Immunization with HF10 inhibited HSV-2 replication in the mouse vagina, reduced local inflammation, controlled emergence of neurological dysfunctions of HSV-2 infection, and increased survival. In HF10-immunized mice, we observed rapid and increased production of interferon-γ in the vagina in response to HSV-2 infection, and numerous CD4(+) and a few CD8(+) T cells localized to the infective focus. CD4(+) T cells invaded the mucosal subepithelial lamina propria. Thus, the protective effect of HF10 was related to induction of cellular immunity, mediated primarily by Th1 CD4(+) cells. These data indicate that the live attenuated HSV-1 mutant strain HF10 is a promising candidate antigen for a vaccine against genital herpes caused by HSV-2.
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    • "In a trial comparing the effects of intensive versus standard STI care and treatment, a lower but not significantly different HIV seroconversion rate was noted in participants randomized to the intensive care regimen (Ghys et al., 2001). Two recent largescale trials showed no evidence for an effect of HSV2 suppressive therapy on HIV acquisition (Celum et al., 2008; Watson-Jones et al., 2008). HSV2 suppressive therapy was also unable to prevent transmission of HIV from infected to uninfected partners, despite a reduction in their HIV viral load (Celum et al., 2010). "
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    • "Close to three years after its publication and six years after the papers were delivered, much of the information in the book likely will be familiar to individuals in the fields of HIV and infectious diseases (ID). Some information is outdated; for example, since the book was published, the efficacy of male circumcision in reducing the risk of HIV infection has been confirmed by three clinical trials (Auvert et al. 2005; Bailey et al. 2007; Gray et al. 2007), and the role of HSV-2 in the spread or acquisition of HIV infection has diminished (Celum et al. 2008 and 2010). Unfortunately , much of the information presented in the book remains accurate. "
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