Impact of aciclovir on ulcer healing, lesional, genital and plasma HIV-1 RNA among patients with genital ulcer disease in Malawi.
OBJECTIVE
By a randomised, double-blind, placebo-controlled trial of aciclovir 800 mg twice daily for 5 days added to the syndromic management of genital ulcer disease (GUD) to determine the impact on ulcer healing and HIV outcomes.


METHODS
Patients presenting with GUD in Malawi were evaluated for HIV and herpes simplex virus type-2 (HSV-2) serologies, ulcer aetiology, lesional, genital and plasma HIV-1 RNA and CD4+ count. Patients were followed up at days 2, 4, 7, 14 and 28. The primary study outcome was ulcer healing at day 14, with secondary outcomes being lesional and genital HIV-1 shedding at day 14 and HIV-1 plasma viral load at day 28 among HIV-1/HSV-2 co-infected individuals.


RESULTS
Four hundred and twenty-two patients (74% male) were randomised (208 to aciclovir, 214 to placebo), of whom 61% were HIV-1 seropositive and 72% HSV-2 seropositive; 67% (267/398) had HSV-2 ulcers. 85% of ulcers were healed at day 14 with no difference between treatment arms (risk ratio (RR)=1.02, 95% CI 0.93 to 1.11). Among 244 HIV-1/HSV-2 co-infected individuals, aciclovir reduced lesional HIV-1 RNA (adjusted RR=0.64, 95% CI 0.41 to 0.99) and seminal HIV-1 RNA (adjusted RR=0.59, 95% CI 0.40 to 0.88), but not cervical HIV-1 RNA or plasma HIV-1 RNA.


CONCLUSIONS
Episodic HSV treatment with aciclovir added to syndromic management did not produce a significant clinical benefit in this African population.
Phiri
Sam
S
Lighthouse Centre, Kamuzu Central Hospital, Lilongwe, Malawi. samphiri@lighthouse.org.mw
Hoffman
Irving F
IF
Weiss
Helen A
HA
Martinson
Francis
F
Nyirenda
Naomi
N
Kamwendo
Debbie
D
Fiscus
Susan A
SA
Chen
Cheng-Yen
CY
Miller
William C
WC
van der Hoeven
Len
L
Chilongozi
David
D
Cohen
Myron S
MS
Mayaud
Philippe
P
D000212:Acyclovir / Q000627:therapeutic use*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005831:Genital Diseases, Female / Q000150:complications / Q000188:drug therapy*; D005832:Genital Diseases, Male / Q000150:complications / Q000188:drug therapy*; D006679:HIV Seropositivity / Q000150:complications; D015497:HIV-1 / Q000235:genetics; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy; D018258:Herpesvirus 2, Human; D006801:Humans; D008295:Malawi; D008297:Male; D055118:Medication Adherence; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D014456:Ulcer / Q000188:drug therapy*; D019562:Viral Load; D055815:Young Adult
D000998:Antiviral Agents; D012367:RNA, Viral; D000212:Acyclovir