title: Impact of aciclovir on ulcer healing, lesional, genital and plasma HIV-1 RNA among patients with genital ulcer disease in Malawi.
abstract: 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.
authors.affiliation: Lighthouse Centre, Kamuzu Central Hospital, Lilongwe, Malawi. samphiri@lighthouse.org.mw
authors.forename: Sam
authors.initials: S
authors.lastname: Phiri
authors.forename: Irving F
authors.initials: IF
authors.lastname: Hoffman
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.forename: Francis
authors.initials: F
authors.lastname: Martinson
authors.forename: Naomi
authors.initials: N
authors.lastname: Nyirenda
authors.forename: Debbie
authors.initials: D
authors.lastname: Kamwendo
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Chen
authors.forename: William C
authors.initials: WC
authors.lastname: Miller
authors.forename: Len
authors.initials: L
authors.lastname: van der Hoeven
authors.forename: David
authors.initials: D
authors.lastname: Chilongozi
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Philippe
authors.initials: P
authors.lastname: Mayaud
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D000212:Acyclovir