Herpes Simplex Virus (HSV) Suppression with Valacyclovir Reduces Rectal and Blood Plasma HIV‐1 Levels in HIV‐1/HSV‐2–Seropositive Men: A Randomized, Double‐Blind, Placebo‐Controlled Crossover Trial

Zuckerman, Richard A.; Lucchetti, Aldo; Whittington, William L. H.; Sánchez, Jorge; Coombs, Robert W.; Zuñiga, Rosario; Magaret, Amalia; Wald, Anna; Corey, Lawrence; Celum, Connie

doi:10.1086/522523

Cited by 173 publications

(164 citation statements)

References 41 publications

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“…Although the present report and other smaller trials conducted among women in Burkina Faso and Thailand, and one conducted among homosexual men in Peru, have shown reductions in plasma and genital or rectal HIV viral loads using aciclovir or valaciclovir [42,43], two recently published randomized controlled trials have shown that daily aciclovir does not reduce the risk of HIV acquisition in HSV-2 seropositive, HIV-seronegative individuals. The necessary reduction in the frequency of genital HIV RNA shedding in order to reduce sexual transmission of HIV is unclear.…”

Section: Discussioncontrasting

confidence: 65%

Aciclovir, herpes viruses and HIV: a never-ending story

Volpi¹,

Sarrecchia

Sordillo

2009

Expert Review of Anti-infective Therapy

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HIV infection continues to be among the leading causes of morbidity and mortality, especially in Africa. The prevalence of herpes simplex virus type 2 (HSV-2) has already reached high seroprevalence of up to 90% in HIV-seropositive individuals, and HSV-2 is now the leading cause of genital ulcer disease in both developing and developed countries. The role of HSV-2 as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV diffusion, also facilitating HIV spread among the low-risk population who have stable long-term sexual partnerships. To date, no vaccine to prevent HSV-2 acquisition or reactivation has been developed, although antivirals have been shown to be safe and effective in reducing HSV-2 shedding frequency and the duration of genital ulcer disease. The paper under evaluation confirms the favorable effect of therapies aimed at suppressing HSV-2 reactivation in HIV-seropositive patients on HIV plasma and vaginal load. In this study, aciclovir 400 mg twice daily was able to significantly reduce plasma and genital HIV RNA, the frequency of HIV shedding, genital HSV-2 DNA and the frequency of genital ulcerations. These results suggest that HSV-2 control with low-cost aciclovir can play an important role in reducing HIV spread, mainly in developing countries, where costs limit the use of highly active antiretroviral therapy

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Section: Discussioncontrasting

confidence: 65%

Aciclovir, herpes viruses and HIV: a never-ending story

Volpi¹,

Sarrecchia

Sordillo

2009

Expert Review of Anti-infective Therapy

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“…For instance, more than 3200 mg of acyclovir taken per day was associated with improved survival in a meta-analysis of studies among advanced AIDS patients in the pre-HAART era (80), and 800 mg of acyclovir taken twice daily produced decreases in cervicovaginal HIV shedding in HSV-2-HIV-coinfected women in Thailand (81). Valacyclovir may be preferable to study over acyclovir due to its improved bioavailability (54.5% versus 15% to 30%) and significantly decreased pill burden (82); indeed, among women in Burkina Faso (Africa) and MSM in Peru, 500 mg of valacyclovir taken twice daily was associated with reductions in plasma HIV RNA levels of up to 0.53 log 10 copies/mL (47,48). Furthermore, the finding that HSV-2-specific immune responses persist in genital skin long after resolution of clinical symptoms suggests that prolonged doses of such high-potency drugs may be required to fully suppress the effects of HSV-2 infection (83).…”

Section: Implications For Clinical Practice and Researchmentioning

confidence: 99%

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Tan

Kaul

Walsmley

2009

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are among the most common coinfections seen in individuals infected with HIV-1. Most research on HSV-HIV coinfection has focused on HSV-2, and in particular, on its impact on HIV transmission. HSV-2 is associated with micro- and macroulcerations in genital mucosal surfaces, increased numbers of HIV target cells in genital mucosal tissue and increases in plasma HIV viral load of up to 0.5 log10copies/mL, such that HSV-2 infection increases the risk of both HIV acquisition and transmission. Because plasma HIV RNA levels are a major determinant of rates of CD4 cell decline, HSV-2 coinfection may also adversely affect the progression of HIV disease. Anti-HSV medications have in fact been associated with reciprocal decreases in HIV viral load in short-term studies. These findings have led to the development of several clinical trials of HSV-2 suppression as strategies for preventing HIV transmission and slowing the rate of HIV disease progression. HSV-1 coinfection has largely been ignored from this growing body of research, yet there are several reasons that this coinfection remains an important issue for study. First, the seroprevalence of HSV-1 is consistently higher than that of HSV-2 among both HIV-infected and HIV-uninfected populations, underscoring the relevance of HSV-1 coinfection to the majority of HIV-infected persons. Second, pre-existing HSV-1 antibodies in individuals may modulate the course of subsequently acquired HSV-2 infection; the implications of such changes on HSV-HIV coinfection remain unexplored. Third, HSV-1 and HSV-2 are closely related viruses that share 83% genetic homology. Their virological and pathobiological similarities suggest that their implications on HIV pathogenesis may be similar as well. Finally, HSV-1 is becoming increasingly relevant because the incidence of genital HSV-1 has risen. Although genital herpes is traditionally associated with HSV-2, recent studies have shown that the majority of serologically confirmed primary genital herpes in some settings is attributable to HSV-1. Because the genital tract is an important site of biological interaction between HSV and HIV, this epidemiological change may be clinically important.

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“…In particular, ACV/vACV treatments are associated with a reduction of HIV-1 load in plasma, semen, cervico-vaginal secretions, and rectal swabs (3,9,11,20,27,45,46) and in plasma during pregnancy (10). Also, several clinical studies, as well as two meta-analyses of a total of 15 randomized clinical studies, demonstrate that ACV/vACV treatment delays progression to AIDS and prolongs the patient's survival (14,22).…”

mentioning

confidence: 99%

Exploiting the Anti-HIV-1 Activity of Acyclovir: Suppression of Primary and Drug-Resistant HIV Isolates and Potentiation of the Activity by Ribavirin

Vanpouille

Lisco

Introini

et al. 2012

Antimicrob Agents Chemother

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ABSTRACTMultiple clinical trials have demonstrated that herpes simplex virus 2 (HSV-2) suppressive therapy using acyclovir (ACV) or valacyclovir in HIV-1/HSV-2-infected persons increased the patient's survival and decreased the HIV-1 load. It has been shown that the incorporation of ACV-monophosphate into the nascent DNA chain instead of dGMP results in the termination of viral DNA elongation and directly inhibits laboratory strains of HIV-1. We evaluated here the anti-HIV activity of ACV against primary HIV-1 isolates of different clades and coreceptor specificity and against viral isolates resistant to currently used drugs, including zidovudine, lamivudine, nevirapine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs), a fusion inhibitor, and two protease inhibitors. We found that, at clinically relevant concentrations, ACV inhibits the replication of these isolates in human tissues infectedex vivo. Moreover, addition of ribavirin, an antiviral capable of depleting the pool of intracellular dGTP, potentiated the ACV-mediated HIV-1 suppression. These data warrant further clinical investigations of the benefits of using inexpensive and safe ACV alone or in combination with other drugs against HIV-1, especially to complement or delay highly active antiretroviral therapy (HAART) initiation in low-resource settings.

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Herpes Simplex Virus (HSV) Suppression with Valacyclovir Reduces Rectal and Blood Plasma HIV‐1 Levels in HIV‐1/HSV‐2–Seropositive Men: A Randomized, Double‐Blind, Placebo‐Controlled Crossover Trial

Cited by 173 publications

References 41 publications

Aciclovir, herpes viruses and HIV: a never-ending story

Aciclovir, herpes viruses and HIV: a never-ending story

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Exploiting the Anti-HIV-1 Activity of Acyclovir: Suppression of Primary and Drug-Resistant HIV Isolates and Potentiation of the Activity by Ribavirin

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