Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial

Lingappa, Jairam R.; Baeten, Jared M.; Wald, Anna; Hughes, James P.; Thomas, Katherine K.; Mujugira, Andrew; Mugo, Nelly; Bukusi, Elizabeth A.; Cohen, Craig R.; Katabira, Elly; Ronald, Allan; Kiarie, James; Farquhar, Carey; Stewart, Grace John; Makhema, Joseph; Essex, M.; Were, Edwin; Fife, Kenneth H.; Bruyn, Guy de; Gray, Glenda; McIntyre, James; Manongi, Rachel; Kapiga, Saidi; Coetzee, David; Allen, Susan; Inambao, Mubiana; Kayitenkore, Kayitesi; Karita, Etienne; Kanweka, William; Delany, Sinéad; Rees, Helen; Vwalika, Bellington; Magaret, Amalia; Wang, Richard S.; Kidoguchi, Lara; Barnes, Linda; Ridzon, Renée; Corey, Lawrence; Celum, Connie

doi:10.1016/s0140-6736(09)62038-9

Cited by 144 publications

(128 citation statements)

References 48 publications

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“…and treatment (9). HSV-2 treatment not only decreases the frequency and severity of HSV-2 recurrence and shedding, but also modestly decreases HIV viral load and genital secretions (10). However, there are limited data to inform clinicians of the specific factors associated with HSV-2/syphilis serostatus in HIV-positive MSM in China.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human Immunodeficiency Virus Positive Men Who Have Sex with Men: a Cross-Sectional Study in Northeast China

Chu

et al. 2017

Jpn J Infect Dis

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Section: Introductionmentioning

confidence: 99%

Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human Immunodeficiency Virus Positive Men Who Have Sex with Men: a Cross-Sectional Study in Northeast China

Chu

et al. 2017

Jpn J Infect Dis

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“…All three viruses often infect the same host and likely influence each other's dynamics and replication. For HSV-2, among HIV-infected people, the seroprevalence is ϳ70 to 90% (50,76), and seminal shedding of HSV is associated with higher HIV RNA genital levels (8,53,64). Also, HSV-2 seropositivity of the source partners is associated with HIV transmission among men who have sex with men (MSM) (13); however, the use of acyclovir for chronic HSV infection among HIVinfected individuals does not reduce HIV transmission to their partners (14).…”

mentioning

confidence: 99%

Associations between Virologic and Immunologic Dynamics in Blood and in the Male Genital Tract

Gianella

Strain

Rought

et al. 2012

J Virol

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To determine the influence of asymptomatic genital viral infections on the cellular components of semen and blood, we evaluated the associations between the numbers and activation statuses of CD4 ؉ and CD8 ؉ T lymphocytes in both compartments and the seminal levels of cytomegalovirus (CMV), herpes simplex virus (HSV), and human immunodeficiency virus 1 (HIV). Paired blood and semen samples were collected from 36 HIV-infected antiretroviral-naïve individuals and from 40 HIV-uninfected participants. We performed multiparameter flow cytometry analysis (CD45, CD45RA, CD3, CD4, CD8, and CD38) of seminal and blood cellular components and measured HIV RNA and CMV and HSV DNA levels in seminal and blood plasma by real-time PCR. Compared to HIV-uninfected participants, in the seminal compartment HIV-infected participants had higher levels of CMV (P < 0.05), higher numbers of total CD3 ؉ (P < 0.01) and CD8 ؉ subset (P < 0.01) T lymphocytes, and higher CD4 ؉ and CD8 ؉ T lymphocyte activation (RA-CD38 ؉ ) (P < 0.01). Seminal CMV levels positively correlated with absolute numbers of CD4 ؉ and CD8 ؉ T cells in semen (P < 0.05) and with the activation status of CD4 ؉ T cells in semen and in blood (P < 0.01). HIV levels in semen (P < 0.05) and blood (P < 0.01) were positively associated with T-cell activation in blood. Activation of CD8 ؉ T cells in blood remained an independent predictor of HIV levels in semen in multivariate analysis. The virologic milieu in the male genital tract strongly influences the recruitment and activation of immune cells in semen and may also modulate T-cell immune activation in blood. These factors likely influence replication dynamics, sexual transmission risk, and disease outcomes for all three viruses.

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“…ompelling clinical evidence has demonstrated that the treatment of HIV-1-infected persons with acyclovir (ACV) or its prodrug valacyclovir (vACV) reduces HIV-1 load and delays HIV-1 disease progression (20). 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).…”

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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Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial

Cited by 144 publications

References 48 publications

Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human Immunodeficiency Virus Positive Men Who Have Sex with Men: a Cross-Sectional Study in Northeast China

Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human Immunodeficiency Virus Positive Men Who Have Sex with Men: a Cross-Sectional Study in Northeast China

Associations between Virologic and Immunologic Dynamics in Blood and in the Male Genital Tract

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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