Acquired Immunodeficiency Syndrome: Berrey MM

Corey L, Berrey MM. · Fred Hutchinson Cancer Research Center, Program in Infectious Diseases, University of Washington, Seattle 98109-1024, USA. · Adv Exp Med Biol. · Pubmed #10549394 No free full text.

Abstract: Initiation of antiretroviral therapy during primary HIV-1 infection may well redefine the course of the disease by controlling the burst of viral replication and subsequent immune dysfunction. At present, treatment of acute primary HIV-1 should remain largely in the domain of clinical investigation. There are significant problems in providing constant vigilance to medication and subsequent viral suppression. Only clinical trials can define the relative benefit of initiating antiretrovirals during this stage of infection.

Berrey MM, Schacker T, Collier AC, Shea T, Brodie SJ, Mayers D, Coombs R, Krieger J, Chun TW, Fauci A, Self SG, Corey L. · Department of Medicine, University of Washington, Seattle, WA, USA. · J Infect Dis. · Pubmed #11319682 No free full text.

Abstract: Immunologic data supporting immediate antiretroviral therapy in primary human immunodeficiency virus type 1 (HIV-1) infection are emerging; however, clinical benefit has not been demonstrated. The clinical and virologic course of 47 patients who were enrolled from September 1993 through June 1996 and who were not initially treated with potent therapy was compared with the course of 20 patients who immediately began therapy with zidovudine, lamivudine, and indinavir. Demographic and baseline laboratory data were comparable. During 78 weeks of follow-up, the early-treatment cohort showed a reduced frequency of opportunistic infections (5% vs. 21.3%; relative risk, 0.11; P=.02), less frequent progression to AIDS (13% vs. 0%), and significantly less frequent nonopportunistic mucocutaneous disorders and respiratory infections (P<.01). Plasma HIV-1 RNA levels were <50 copies/mL in all patients who continued therapy; however, after 9--12 months, HIV-1 remained detectable in latently infected CD4(+) T cells and in lymph node mononuclear cells. Combination antiretroviral therapy during primary HIV-1 infection demonstrated a decreased frequency of minor opportunistic infections, mucocutaneous disorders, and respiratory infections and reduced progression to AIDS.

Malhotra U, Holte S, Dutta S, Berrey MM, Delpit E, Koelle DM, Sette A, Corey L, McElrath MJ. · Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109, USA. · J Clin Invest. · Pubmed #11181650 links to  free full text

Abstract: HIV-1-infected patients treated early with combination antiretrovirals respond favorably, but not all maintain viral suppression and improved HIV-specific Th function. To understand if genetic factors contribute to this variation, we prospectively evaluated over 18 months 21 early-treated patients stratified by alleles of class II haplotypes. All seven subjects with the DRB1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus suppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher mean lymphoproliferation and IFN-gamma secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were identified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 haplotype, have an important impact on virologic and immunologic responses. The advantage of the haplotype may relate to selection of key HIV-1 Th1 epitopes in highly conserved regions with avid binding to class II molecules. Eliciting responses to the promiscuous epitope region may be beneficial in vaccine strategies.