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1.
J Infect Dis ; 180(2): 320-9, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10395845

ABSTRACT

Antiretroviral therapy commenced during primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) may limit the extent of viral replication and prevent early loss of HIV-specific CD4 lymphocyte function. We studied the effect of current standard therapy (2 nucleoside analogues and a protease inhibitor) in 16 patients with symptomatic PHI. In the 13 patients who completed 1 year of treatment, plasma HIV RNA was <50 copies/mL and median CD4 cell counts were comparable to HIV-uninfected controls, with naive (CD45RA+CD62L+), primed (CD45RO+), and T cell receptor Vbeta subsets all within normal ranges. However, HIV-1 DNA levels in treated and untreated PHI patients were similar. Furthermore, CD8 cell counts remained elevated, including activated (CD38+HLA-DR+), replicating (Ki-67+), and cytotoxic (perforin+CD28-) lymphocytes. In conclusion, early antiretroviral therapy resulted in clearance of viremia and prevented loss of crucial CD4 subsets. The persistence of HIV-1 DNA together with increased CD8 T lymphocyte turnover and activation indicate continued expression of viral antigens.


Subject(s)
Anti-HIV Agents/therapeutic use , CD4-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , HIV-1/physiology , T-Lymphocyte Subsets/immunology , Adult , CD8-Positive T-Lymphocytes/immunology , Cohort Studies , DNA, Viral/blood , Drug Therapy, Combination , HIV Antibodies/blood , HIV Infections/immunology , HIV Infections/virology , Humans , Indinavir/therapeutic use , Lamivudine/therapeutic use , Leukocytes, Mononuclear/virology , Lymphocyte Activation , Male , Prospective Studies , RNA, Viral/blood , Viremia/drug therapy , Viremia/virology , Zidovudine/therapeutic use
2.
AIDS ; 12(2): 175-82, 1998 Jan 22.
Article in English | MEDLINE | ID: mdl-9468366

ABSTRACT

OBJECTIVES: To evaluate the impact of therapeutic immunization with p24 virus-like particle (VLP) and zidovudine (ZDV) on p24 antibody titre (primary endpoint), CD4+ cell counts, cellular responses to the immunogen and recall antigens, and viral load (secondary endpoints) in subjects with asymptomatic HIV infection and CD4+ counts greater than 400 x 10(6) cells/l. DESIGN: A double dummy, double-blind randomized placebo-controlled Phase II trial of the therapeutic vaccine p24-VLP, with or without ZDV. METHODS: ZDV-naive subjects were randomized to one of three groups for 6 months: group A, ZDV 200 mg three times daily plus intramuscular administration of alum adjuvant monthly; group B, ZDV 200 mg three times daily plus p24-VLP (500 microg) in intramuscular alum monthly; group C, placebo capsules plus p24-VLP (500 microg) in intramuscular alum monthly. Subjects were followed for a further 6 months. RESULTS: Sixty-one patients received vaccinations. The mean CD4+ cell counts pretherapy for groups A, B, and C were 605 +/- 25, 668 +/- 43, and 583 +/- 30 x 10(6) cells/l, respectively. Treatment was well tolerated. At both 24 and 52 weeks there were no significant differences between the treatment groups in terms of antibody responses to p24, CD4+ or CD8+ cell counts, viral load, T-cell responses to p24, p17, recall antigen or mitogen, or markers of immune activation, despite induction of antibody and proliferative responses to the carrier protein of the vaccine. CONCLUSION: Vaccination with p24-VLP was well tolerated. p24-VLP either alone or in combination with ZDV did not significantly alter either antibody or proliferative responses to p24, or CD4+ cell number, immune activation or viral load over 12 months.


Subject(s)
AIDS Vaccines/therapeutic use , Anti-HIV Agents/therapeutic use , HIV Core Protein p24/therapeutic use , HIV Infections/therapy , HIV-1 , Zidovudine/therapeutic use , AIDS Vaccines/adverse effects , Adult , Anti-HIV Agents/adverse effects , CD4 Lymphocyte Count , Combined Modality Therapy , Disease Progression , Female , HIV Antibodies/blood , HIV Core Protein p24/adverse effects , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , HIV-1/drug effects , HIV-1/immunology , HIV-1/physiology , Humans , Hypersensitivity, Delayed , Lymphocyte Count , Male , Middle Aged , Treatment Outcome , Vaccination , Viral Load , Zidovudine/adverse effects
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