title: HIV-1 coreceptor switch during 2 years of structured treatment interruptions.
abstract: The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral therapy (HAART). The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20%) was used for data interpretation. At baseline, 9/12 subjects (75.0%) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5-X4, one X4-R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Baroncelli
authors.forename: C M
authors.initials: CM
authors.lastname: Galluzzo
authors.forename: M
authors.initials: M
authors.lastname: Andreotti
authors.forename: M F
authors.initials: MF
authors.lastname: Pirillo
authors.forename: V
authors.initials: V
authors.lastname: Fragola
authors.forename: L E
authors.initials: LE
authors.lastname: Weimer
authors.forename: M
authors.initials: M
authors.lastname: Giuliano
authors.forename: S
authors.initials: S
authors.lastname: Vella
authors.forename: L
authors.initials: L
authors.lastname: Palmisano
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D016896:Treatment Outcome; D056189:Viral Tropism
chemical_list: D044966:Anti-Retroviral Agents; C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D004279:DNA, Viral; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4