title: Prognostic Value of HIV-1 RNA on CD4 Trajectories and Disease Progression Among Antiretroviral-Naive HIV-Infected Adults in Botswana: A Joint Modeling Analysis.
abstract: Although HIV-1 RNA levels are measured at the time of initial diagnosis, the results are not used for the clinical follow-up of the patients. This study evaluates the prognostic value of the baseline HIV-1 RNA levels (above or below 10,000 copies/ml) on rate of disease progression, among antiretroviral therapy (ART)-naive patients in Botswana. A prospective cohort of 436 HIV-infected ART-naive adults with baseline CD4 > 400 cells/mm(3) were followed quarterly for 5 years in an urban clinic in Botswana. Baseline HIV-1 RNA levels and longitudinal CD4(+) T-cell count data were analyzed, using mixed-effects regression jointly modeled with the times to a composite endpoint defined by AIDS-defining clinical conditions or death. During 1,547 person-years (PYs) follow-up time, 106 individuals became eligible for ART initiation (incidence rate: 0.07 PYs) and 6 participants died of AIDS-related illness. There were 203 (47%) individuals with baseline HIV-1 RNA <10,000 copies/ml and 233 (53%) individuals with baseline RNA >10,000 copies/ml. The slope of the predicted CD4 trajectory for individuals with baseline HIV-1 RNA >10,000 copies/ml is 30% steeper than that for those with baseline RNA <10,000. The hazard of reaching the composite endpoint for the individuals with baseline HIV-1 RNA >10,000 copies/ml was 2.3 (95% confidence interval: 1.5-3.0) times higher than that for those with baseline HIV-1 RNA <10,000 copies/ml. CD4 decline in individuals with HIV-1 RNA >10,000 copies/ml is much faster than that in those with RNA <10,000. The elevated HIV-1 RNA can be used as a marker to identify individuals at risk of faster disease progression.
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.
authors.forename: Mansour
authors.initials: M
authors.lastname: Farahani
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Vladimir
authors.initials: V
authors.lastname: Novitsky
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|3 Harvard Medical School , Boston, Massachusetts.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Hermann
authors.initials: H
authors.lastname: Bussmann
authors.affiliation: 2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Sikhulile
authors.initials: S
authors.lastname: Moyo
authors.affiliation: 2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Rosemary M
authors.initials: RM
authors.lastname: Musonda
authors.affiliation: 4 Health Systems Trust , Midrand, South Africa .
authors.forename: Themba
authors.initials: T
authors.lastname: Moeti
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Makhema
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Richard
authors.initials: R
authors.lastname: Marlink
mesh_terms: D000328:Adult; D001902:Botswana; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load; D055815:Young Adult
chemical_list: D012367:RNA, Viral
references.citation: J Clin Oncol. 2010 Jun 1;28(16):2796-801
references.pmid: 20439643
references.citation: PLoS Pathog. 2011 Nov;7(11):e1002321
references.pmid: 22072960
references.citation: Viruses. 2011 Mar;3(3):204-16
references.pmid: 21994727
references.citation: PLoS One. 2009 Jun 17;4(6):e5950
references.pmid: 19536329
references.citation: AIDS. 2014 Apr 24;28(7):1021-9
references.pmid: 24691205
references.citation: PLoS One. 2013;8(2):e55747
references.pmid: 23418455
references.citation: J Infect Dis. 2000 Mar;181(3):872-80
references.pmid: 10720507
references.citation: N Engl J Med. 2000 Mar 30;342(13):921-9
references.pmid: 10738050
references.citation: Evolution. 2013 Oct;67(10):2769-82
references.pmid: 24094332
references.citation: Science. 1996 May 24;272(5265):1167-70
references.pmid: 8638160
references.citation: AIDS. 2009 Jul 17;23(11):1397-404
references.pmid: 19381076
references.citation: J Infect Dis. 2001 Jan 15;183(2):206-212
references.pmid: 11120927
references.citation: Ann Intern Med. 1997 Jun 15;126(12):946-54
references.pmid: 9182471