title: Long-term follow-up of HIV seroconverters in microbicide trials - rationale, study design, and challenges in MTN-015.
abstract: As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort.
  
  
  
  Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing.
  
  
  
  MTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness.
  
  
  
  Enrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women.
authors.affiliation: a Division of Infectious Diseases , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
authors.affiliation: b MTN Statistical and Data Management Center , Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
authors.forename: Marla
authors.initials: M
authors.lastname: Husnik
authors.affiliation: c Department of Epidemiology , University of California , Los Angeles , CA , USA.
authors.forename: Pamina M
authors.initials: PM
authors.lastname: Gorbach
authors.affiliation: d FHI360 , Durham, NC , USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Levy
authors.affiliation: a Division of Infectious Diseases , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Urvi
authors.initials: U
authors.lastname: Parikh
authors.affiliation: e Microbicide Trials Network , Magee-Womens Research Institute , Pittsburgh , PA , USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Livant
authors.affiliation: f HIV Prevention Research Unit , South African Medical Research Council , Durban , South Africa.
authors.forename: Arendevi
authors.initials: A
authors.lastname: Pather
authors.affiliation: g College of Medicine-John Hopkins University Research Project , Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Bonus
authors.initials: B
authors.lastname: Makanani
authors.affiliation: h UZ-UCSF Collaborative Research Programme , University of Zimbabwe , Harare , Zimbabwe.
authors.forename: Felix
authors.initials: F
authors.lastname: Muhlanga
authors.affiliation: i Centre for Infectious Disease Research in Zambia , Lusaka , Zambia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kasaro
authors.affiliation: j UNC Project - Tidziwe Centre , Kamuzu Central Hospital , Lilongwe , Malawi.
authors.forename: Francis
authors.initials: F
authors.lastname: Martinson
authors.affiliation: k Division of AIDS , National Institutes of Health , Bethesda , MD , USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Elharrar
authors.affiliation: b MTN Statistical and Data Management Center , Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Balkus
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002985:Clinical Protocols; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D065129:Pre-Exposure Prophylaxis; D011247:Pregnancy; D011256:Pregnancy Outcome; D012107:Research Design; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents
keywords: HIV; clinical trial design; cohort Study; drug resistance; microbicides; pre-exposure prophylaxis; prevention; seroconversion