title: HIV disease progression in seroconvertors from the CAPRISA 004 tenofovir gel pre-exposure prophylaxis trial.
abstract: BACKGROUND
  Although antiretroviral pre-exposure prophylaxis prevents HIV acquisition, it is not known if it alters HIV disease progression. This study assesses whether tenofovir gel impacted on disease progression among CAPRISA 004 microbicide trial seroconvertors.
  
  
  METHODS
  Eighty-three seroconvertors from the tenofovir and placebo gel arms of the CAPRISA 004 trial were monitored prospectively for a minimum of 2 years by CD4 count and viral load (VL). Linear mixed models were fitted to HIV VL, and log rank test was used to compare time to reach CD4 counts of <350 cells per microliter.
  
  
  RESULTS
  Median 2-week postinfection VL was 4.74 and 4.45 log copies per milliliter in women assigned to tenofovir gel (n = 32) and placebo gel (n = 51) (P = 0.189). Corresponding 12-month postinfection VLs were 4.24 and 3.70 log copies per milliliter (P = 0.016). After adjusting for clinical and behavioral characteristics and protective HLA alleles, mean VLs within the first 2 years were 4.51 and 4.02 log copies per milliliter in women from the tenofovir and placebo arms (P = 0.013). Among women with vaginal tenofovir measurements, mean VLs were 4.53 and 4.60 log copies per milliliter in those with detectable versus undetectable levels (P = 0.840). Overall mean CD4 counts were 463 and 514 cells per microliter in women assigned to tenofovir and placebo (P = 0.290). Thirty-two women (38.6%) reached CD4 counts of <350 cells per microliter at median 9.4 months postinfection, 13 (40.6%) from the tenofovir and 19 (37.3%) from the placebo arms (P = 0.786).
  
  
  CONCLUSIONS
  Tenofovir gel had no impact on postinfection CD4 counts or the rate of CD4 decline. Although seroconvertors from the tenofovir arm experienced higher VLs, this did not result in a need for earlier antiretroviral therapy.
authors.affiliation: *Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa; †Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; ‡Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; §Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; ‖National Health Laboratory Service, South Africa; ¶AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa; and #Department of Epidemiology, Columbia University, New York, NY USA.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Garrett
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.forename: Nivashnee
authors.initials: N
authors.lastname: Naicker
authors.forename: Vivek
authors.initials: V
authors.lastname: Naranbhai
authors.forename: Sengeziwe
authors.initials: S
authors.lastname: Sibeko
authors.forename: Natasha
authors.initials: N
authors.lastname: Samsunder
authors.forename: Clive
authors.initials: C
authors.lastname: Gray
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Quarraisha
authors.initials: Q
authors.lastname: Abdool-Karim
authors.forename: Salim S
authors.initials: SS
authors.lastname: Abdool-Karim
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005782:Gels; D015658:HIV Infections / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D065129:Pre-Exposure Prophylaxis; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000068698:Tenofovir; D014621:Vagina
chemical_list: D005782:Gels; D063065:Organophosphonates; D010919:Placebos; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine