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Antiretrovirals Do Not Stop HSV Shedding in Genital or Anal Tract in Canada
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52nd ICAAC, September 9-12, 2012, San Francisco
Mark Mascolini
Antiretroviral therapy did not stop herpes simplex virus (HSV) 1 or 2 reactivation and shedding in the mouth or anal or genital tract of HIV-positive people, according to results of a month-long study in Canada [1]. In a separate study of people not taking antiretrovirals, HSV-2 infection shortened the time to a CD4 count below 350 or starting combination antiretroviral therapy (cART), and the investigators believe starting cART drove that association.
HIV and HSV-1 and 2 have complex interactions. About 70% of HIV-positive people have HSV-2 infection, and about 95% are positive for HSV-1 or HSV-2 [2,3]. HSV-2 raises the risk of HIV infection, and HSV-2 infection boosts HIV load in coinfected people [2,3].
University of Toronto researchers conducted separate studies to answer two questions about HSV-1/2 and HIV. Study 1 aimed to determine whether cART-induced viral suppression affects genital and anal HSV shedding in adults coinfected with HIV and one or both herpes viruses but with minimal HSV symptoms. Study 2 compared annual rates of CD4-count change and the need to start cART in HIV-positive adults with or without HSV-2 and not taking antiretrovirals.
Study 1 enrolled 85 HIV-positive with HSV-1 and/or HSV-2 with no HSV symptoms for 4 months or 2 or fewer HSV episodes per year. Forty-four people had never taken antiretrovirals and 41 were on treatment with a viral load below 50 copies. Every day for 28 days all participants collected oral swabs and sex-specific genital or anal swabs; they stopped collecting swabs if they had confirmed symptomatic HSV reactivation. The primary outcome was the number of days with PCR-detected HSV-1 or 2 in any specimen.
Most people in the cART-naive group (75%) and the treated group (83%) were men, and about two thirds in each group were men who have sex with men (MSM). Age averaged 35.4 in the untreated group and 49.6 in the treated group. While 70% of the untreated group immigrated to Canada, people born in Canada made up half of the treated group. About half in each group were positive for both HSV-1 and 2, and baseline CD4 count lay at about 500 in each group.
Negative binomial regression analysis adjusted for sex, CD4 count, time since HIV diagnosis, and recent immigrant status found no association between HSV-1, HSV-2, or both HSVs and HSV shedding.
The primary objective of study 2 was to compare the annual rate of change in CD4 count in untreated adults with or without HSV-2 infection. Randomized controlled trials showed that 400 mg of acyclovir twice daily slows HIV progression in cART-untreated people coinfected with HIV and HSV-2.
This analysis focused on people with a banked viral load specimen available from a period of 3 or more months in which those people had 3 or more CD4 counts while taking no drugs for HIV or HSV-2. Of the 218 participants, 123 had HSV-2 infection and 95 did not. The HSV-2-positive group had a lower proportion of men than the HSV-2 negative group (61.0% versus 86.3%), and age was higher in the positive group (36.4 versus 33.9 years). MSM made up a lower proportion of the HSV-2-positive group (48.7% versus 79.5%), and a lower proportion of HSV-2-positive people were born in Canada (38.3% versus 57.7%). CD4 counts at baseline were 523 with HSV-2 and 560 without HSV-2.
A time-to-event analysis determined that having HSV-2 doubled the risk of reaching a CD4 count below 350 or starting cART for any reason (estimate 2.07, 95% confidence interval [CI] 1.28 to 3.33, P = 0.003). Having genital herpes symptoms lowered the risk about 30% (estimate 0.71), but that association lacked statistical significance (95% CI 0.43 to 1.16, P = 0.17). Women had a doubled risk of reaching a sub-350 CD4 count or starting cART (estimate 2.00, 95% CI 1.30 to 3.08, P = 0.002). Every 100-cell higher baseline CD4 count lowered the risk of reaching a sub-350 count or starting cART about 30% (estimate 0.71, 95% CI 0.60 to 0.83, P < 0.0001).
Post hoc analysis suggested that the doubled risk of reaching the endpoint with HSV-2 infection was driven by cART initiation, not by reaching a CD4 count under 350. The researchers suggested that might be explained by patient or physician concern about HSV-2 or by HSV-2-associated opportunistic infections not related to CD4 count, such as TB or herpes zoster.
Because of persistent HSV shedding despite cART, the researchers suggested that "trials of anti-HSV drugs for improving HIV outcomes may be warranted in such patients."
References
1. Tan DHS, Raboud JM, Kaul R, Walmsley SL. No impact of suppressive antiretroviral therapy on mucosal shedding of herpes simplex virus types 1 and 2 in HIV co-infected adults. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-1920.
2. Corey L, Wald A, Celum CL, Quinn TC. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Acquir Immune Defic Syndr 2004;35:435-445.
3. Centers for Disease Control and Prevention. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. MMWR. 2009;58(No. RR-4):1-206.
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