Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial

Ouédraogo, Abdoulaye; Nagot, Nicolas; Vergne, Laurence; Konaté, Issouf; Weiss, Helen A.; Defer, Marie-Christine; Foulongne, Vincent; Sanon, Anselme; Andonaba, Jean-Baptiste; Segondy, Michel; Mayaud, Philippe; Perre, Philippe Van de

doi:10.1097/qad.0b013e328010238d

Cited by 86 publications

(75 citation statements)

References 30 publications

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“…We also found that women randomized to valacyclovir had a lower risk of genital HSV DNA shedding, consistent with previous studies [41,42]. In contrast, we did not detect a significant association between valacyclovir and cervical HIV-1 RNA levels or shedding, which is consistent with results from a cohort receiving HAART reported by Ouedraogo et al [43] and an antiretroviral-naive cohort reported by Delany et al [17] but in conflict with 3 other randomized trials conducted in antiretroviral-naive cohorts [12][13][14]. One potential explanation for the lack of association in our study is that a high proportion (.40%) of women in our cohort were not shedding HIV-1 in cervical secretions and had low baseline cervical HIV-1 RNA levels after initiation of ZDV, which reduces cervical HIV-1 RNA levels by 1 log 10 copies/mL after 1 week of ZDV treatment [44].…”

Section: Discussionsupporting

confidence: 92%

Valacyclovir Suppressive Therapy Reduces Plasma and Breast Milk HIV-1 RNA Levels During Pregnancy and Postpartum: A Randomized Trial

Drake¹,

Roxby²,

Ongecha-Owuor

et al. 2011

The Journal of Infectious Diseases

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Section: Discussionsupporting

confidence: 92%

Valacyclovir Suppressive Therapy Reduces Plasma and Breast Milk HIV-1 RNA Levels During Pregnancy and Postpartum: A Randomized Trial

Drake¹,

Roxby²,

Ongecha-Owuor

et al. 2011

The Journal of Infectious Diseases

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“…erpes simplex virus 2 (HSV-2) is one of the most common causes of genital ulcer disease worldwide and epidemiological studies consistently demonstrate a strong link between HSV-2 and the risk for HIV acquisition and transmission (1)(2)(3). The prevalence of HSV-2 infection among people with HIV from sub-Saharan African countries ranges from 50 to 90% (4).…”

mentioning

confidence: 99%

Herpes Simplex Virus 2 (HSV-2) Prevents Dendritic Cell Maturation, Induces Apoptosis, and Triggers Release of Proinflammatory Cytokines: Potential Links to HSV-HIV Synergy

Stefanidou

Ramos

Casullo

et al. 2013

J Virol

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bHerpes simplex virus 2 (HSV-2) may cause frequent recurrences, highlighting its ability to evade host defense. This study tested the hypothesis that HSV-2 interferes with dendritic cell (DC) function as an escape mechanism, which may contribute to enhanced HIV replication in coinfected populations. Immature monocyte-derived human DCs were exposed to live or UV-inactivated HSV-2 or lipopolysaccharide. Little or no increase in the maturation marker CD83 was observed in response to HSV-2 and HSV-2 exposed DCs were impaired in their ability to present antigen (influenza) to T cells. Exposure to UV-inactivated virus stimulated a modest, but significant increase in CD83, suggesting that viral gene expression contributes to the block in DC maturation. The functional impairment of HSV-2-exposed DCs could be partially attributed to the induction of apoptosis. Live and inactivated HSV-2 triggered an increase in the number of early and late apoptotic cells in both the infected and bystander cell populations; apoptosis was associated with a decrease in cellular FLICE-inhibitory protein (c-FLIP). Paradoxically, HSV-2 induced Akt phosphorylation, which typically promotes DC maturation and survival. Despite these aberrant responses, live and inactivated HSV-2 induced the release of cytokines into culture supernatants, which were sufficient to activate HIV-1 replication in latently infected U1 cells. Together, these findings suggest that in the presence of overt or subclinical HSV-2, the function of mucosal DCs would be impaired. These responses may allow HSV to escape immune surveillance but may also promote HIV infection and contribute to the epidemiological link between HIV and HSV.

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“…Interestingly HIV transmission in the WITS case-control study was not associated with the presence of HSV DNA either but the numberswere probablytoo small to determine this 17 . Althoughsuppressive therapy with valaciclovir for 12 weeks was associated with a decrease in the frequency of detection of HSV DNA this had no impact on the frequency of detection or load of HIV-1 in the genital tract in women taking HAART 19 , whereas the same treatment in women not taking HAART was associated with a reduction in both genital tract and plasma HIV-1 viraemia 20 .…”

Section: Subsequently In Vitromentioning

confidence: 95%

Advances and controversies in the prevention of HIV-1 mother-to-child transmission

Taylor

2013

Sri Lanka J Vener

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HIV-1 infection can be transmitted from mother-tochild in utero and intra-partum. In the absence of antiret roviral therapy, chorioa mnioniti s has been associated with transmission risk, as has duration of rupture of membranes. Chlorhexidine vaginal lavage reduced transmissiononce membraneswere ruptured more than 4 hours however antibiotics given in the 2 nd trimester did not reduce transmission. Mode of delivery significantly impacts on transmission in the absenceof antiretroviral therapyand whenzidovudine is given as a monotherapy. Most risk factors are eliminated by highly active antiretroviral therapy (HAART) and transmission rates well below 1% are achievable. The role of pre-labour caesarean section (PLCS) in women with undetectable HIV viral load on HAART is now uncertain.The current major controversy is whether HAART, and especially protease-inhibitor containing regimens, are associated with a significa nt increase risk of severe pre-term delivery. Although some argue the case for full suppression of viral load in all pregnant women, most guidelines maintain an optio n for zidovudine monotherapy if baseline viral load is low and PLCS is the preferred mode of delivery.

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Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial

Abstract: HSV-2 facilitates residual genital HIV-1 replication among dually infected women taking HAART despite HIV-1 suppression at the systemic level.

Cited by 86 publications

References 30 publications

Valacyclovir Suppressive Therapy Reduces Plasma and Breast Milk HIV-1 RNA Levels During Pregnancy and Postpartum: A Randomized Trial

Valacyclovir Suppressive Therapy Reduces Plasma and Breast Milk HIV-1 RNA Levels During Pregnancy and Postpartum: A Randomized Trial

Herpes Simplex Virus 2 (HSV-2) Prevents Dendritic Cell Maturation, Induces Apoptosis, and Triggers Release of Proinflammatory Cytokines: Potential Links to HSV-HIV Synergy

Advances and controversies in the prevention of HIV-1 mother-to-child transmission

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