Effects of valacyclovir on markers of disease progression in postpartum women co-infected with HIV-1 and herpes simplex virus-2.
OBJECTIVE
Herpes simplex virus type 2 (HSV-2) suppression has been shown to reduce HIV-1 disease progression in non-pregnant women and men, but effects on pregnant and postpartum women have not been described.


METHODS
We analyzed data from a cohort of Kenyan women participating in a randomized clinical trial of HSV-2 suppression. Pregnant HIV-1-seropositive, HSV-2-seropositive women who were not eligible for antiretroviral therapy (WHO stage 1-2, CD4>250 cells/µl) were randomized to either 500 mg valacyclovir or placebo twice daily from 34 weeks gestation through 12 months postpartum. Women received zidovudine and single-dose nevirapine for prevention of mother-to-child HIV-1 transmission. HIV-1 progression markers, including CD4 count and plasma HIV-1 RNA levels, were measured serially. Multivariate linear regression was used to compare progression markers between study arms.


RESULTS
Of 148 women randomized, 136 (92%) completed 12 months of postpartum follow-up. While adjusted mean CD4 count at 12 months (565 cells/µl placebo arm, 638 cells/µl valacyclovir arm) increased from antenatal levels in both arms, the mean CD4 count increase was 73 cells/µl higher in the valacyclovir arm than placebo arm (p = 0.03). Mean increase in CD4 count was 154 cells/µl in the valacyclovir arm, almost double the increase of 78 cells/µl in the placebo arm. At 12 months, adjusted HIV-1 RNA levels in the placebo arm increased by 0.66 log(10) copies/ml from baseline, and increased by only 0.21 log(10) copies/ml in the valacyclovir arm (0.40 log(10) copies/ml difference, p = 0.001).


CONCLUSIONS
Women randomized to valacyclovir suppressive therapy during pregnancy and postpartum had greater increases in CD4 counts and smaller increases in plasma HIV-1 RNA levels than women in the placebo arm. Valacyclovir suppression during pregnancy and breastfeeding may improve outcomes and delay antiretroviral therapy for HIV-1/HSV-2 co-infected women.
Department of Medicine, University of Washington, Seattle, Washington, United States of America. aroxby@u.washington.edu
Alison C
AC
Roxby
Alison L
AL
Drake
Francisca
F
Ongecha-Owuor
James N
JN
Kiarie
Barbra
B
Richardson
Daniel N
DN
Matemo
Julie
J
Overbaugh
Sandra
S
Emery
Grace C
GC
John-Stewart
Anna
A
Wald
Carey
C
Farquhar
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human; D006801:Humans; D007630:Kenya; D016014:Linear Models; D019829:Nevirapine / Q000008:administration & dosage; D049590:Postpartum Period / Q000187:drug effects*; D011247:Pregnancy; D012367:RNA, Viral / Q000097:blood; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015215:Zidovudine / Q000008:administration & dosage
D000998:Antiviral Agents; D015415:Biomarkers; D015704:CD4 Antigens; D012367:RNA, Viral; D015215:Zidovudine; D019829:Nevirapine; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir