• Poster 556: In Subjects with Primary HIV Infection, High Levels of HIV RNA Are Present in Oral Fluids, Genital Secretions, Peripheral Blood, and CNS and Are Rapidly Reduced with Combination Antiretroviral Therapy (Authored by C.D. Pilcher, D.C. Shugars, S.A. Fiscus, P. Menezes, S.A. Freel, J. Giner, B. Dean, J.J. Eron Jr., J.L. Lennox, and C.B. Hicks. Univ. of North Carolina at Chapel Hill Sch. of Med.; Univ. of North Carolina at Chapel Hill Sch. of Dentistry; Duke Univ. Med. Ctr., Durham, NC; and Emory Univ., Atlanta, GA)
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• Poster 557: Two-Year Decay Characteristics of PBMC-Associated and Tonsilar HIV RNA and DNA in Acutely HIV-Infected Patients Treated with NFV, ddI, d4T and HU (Authored by M. Fischer, M. Flepp, B. Joos, A. Friedl, H. Sax, H. Kuster, M. Opravil, P. Ott, S. Schnittmann, K. Vanderneulen, P. Gervasoni, R. Weber, R. Cone, and H. Gunthard. Univ. Hosp., Zurich, Switzerland; and Bristol Myers Squibb, Wallingford, CT)
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• Poster 559: Treatment of Primary HIV Infection with ddI, d4T, Nevirapine, and Hydroxyurea -- A Pilot Study (Authored by C. Hicks, J. Eron, J. Lennox, C. Pilcher, S. Fiscus, J. Ottinger, R. Baydo, D. Shugars, J. Giner, P. Menezes, and B. Dean. Duke Univ. Med. Ctr., Durham, NC; Univ. of North Carolina at Chapel Hill; and Emory Univ., Atlanta, GA)
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• Poster 560: Immunologic Characterization of a Cohort with Primary HIV Infection Treated with a Hydroxyurea-Containing Non-PI Antiretroviral Regimen (Authored by J. Demarest, H. Staats, M. Kelly, J. Ottinger, V. Edmundson, J. Mathieson, S. Fiscus, C.D. Pilcher, J. Lennox, J.J. Eron Jr., and C.B. Hicks. Duke Univ. Med. Ctr., Durham, NC; Univ. of North Carolina at Chapel Hill; and Emory Univ., Atlanta, GA)
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Poster 556: In Subjects with Primary HIV Infection, High Levels of HIV RNA Are Present in Oral Fluids, Genital Secretions, Peripheral Blood, and CNS and Are Rapidly Reduced with Combination Antiretroviral Therapy

Poster 556 compared viral load levels in blood, saliva, semen or vaginal cervical secretions (CVL) and cerebral spinal fluid (CSF) during primary infection and after treatment initiation. 14 patients were identified who were HIV RNA or p24 antigen positive, but antibody negative. Median time from symptoms to study entry was 40 days. Prior to therapy, cell free and cell associated viral load in saliva was detectable in 7/8 and 5/8 respectively. Viral load was detectable in 5/6 semen samples, 2/2 CVL samples and 4/4 CSF samples. Saliva and semen viral load levels were significantly higher in patients who presented early rather than later. Patients were started on a regimen of ddI/d4T/HU/NVP (nevirapine). After 24 weeks, 6/11 patients had undetectable (<50 copies/ml) blood viral load. In addition, 7/8 semen, 4/4 saliva, and 4/4 CSF samples had undetectable viral loads. Some patients were lost to follow-up. However, in the patients' follow-up for 6 months, it can be seen that this regimen results in significant reductions in viral load in all compartments studied. This regimen appears to be a viable protease-sparing regimen in primary HIV infection.

Poster 557: Two-Year Decay Characteristics of PBMC-Associated and Tonsilar HIV RNA and DNA in Acutely HIV-Infected Patients Treated with NFV, ddI, d4T and HU

Poster 557 asked whether initiation of treatment in early infection altered viral burden in several compartments differently than when treatment was started in later chronic infection. Eight patients with acute infection (within 120 days of diagnosis) and five patients with early infection (defined as CD4 counts >500, irrespective of time), were started on a regimen consisting of d4T/ddI/HU/NFV (nelfinavir). A third group consisting of patients who had received ZDV/3TC/ritonavir for one year and who had viral loads <50/ml was used as a control group. Plasma viral load, blood cellular HIV RNA and DNA, and tonsilar HIV RNA and DNA levels were all quantitated over a two year period. In all groups there was a rapid first phase decay of viral nucleic acid in cells over the first four weeks, followed by a slower second phase decay over the next year. Although the number of patients was small, there appeared to be more rapid declines in the acute infection group. Overall the decline in tonsilar and blood mononuclear cell RNA and DNA was greater in both the acute and early groups when compared to the later treated group. Since there was no ZDV/3TC/ritonavir group in the acute or early infection treatment strategies, it is unclear whether the study regimen was more effective, or the timing of treatment initiation (and therefore the degree of immune system impairment when treatment was started).

Poster 559: Treatment of Primary HIV Infection with ddI, d4T, Nevirapine, and Hydroxyurea -- A Pilot Study

Poster 560: Immunologic Characterization of a Cohort with Primary HIV Infection Treated with a Hydroxyurea-Containing Non-PI Antiretroviral Regimen

Posters 559 and 560 were companion papers reporting on the virologic and immunologic effects of a non-PI regimen given to patients during primary infection. 14 patients were identified within a median of 35 days of primary HIV infection symptoms. They were all started on a regimen consisting of ddI/d4T/HU/NVP (nevirapine). Median baseline viral load and CD4 count were 250,000/ml and 543/ml respectively. Follow-up after 48 weeks revealed that only five patients were still on the original regimen. Five had changed regimens due to toxicity. Four developed neuropathy. Two were virologic failures and two were lost to follow-up. At week 24, 10/11 had viral loads <400, and 6/11 were <50/ml. At week 48, 12/14 were <50/ml (this included those who switched to other regimens). CD4 count had increased by 20% (223) and CD8 counts had decreased by 15% (-851). Baseline genotyping revealed 2/13 patients with a few mutations consistent with resistance to nucleoside analogues. Several kinds of immunologic tests were also performed. At week 24, the number of activated CD8 cells and memory CD8 cells decreased dramatically (means of -1,070 and -931, respectively). Memory CD4 cells increased by 128 and naive CD4 cells increased by 119. There was a three-fold increase in immune response to Candida and herpes virus type 1 antigens. Immune responses to HIV specific antigens were only detected in three patients. Cytotoxic T-cell (CTL) assays were performed where patient cells were further studied for their responses to HIV specific proteins. CTL responses were reported in four patients. CTL response was primarily to HIV gag proteins and not to other HIV antigens. The CTL response appears to be somewhat weaker in those patients receiving HU. This study again demonstrates the potency (as measured by viral load reduction) of d4T/ddI/HU/NVP regimen in primary infection. In addition, several immunologic parameters were found to be improved. Whether this regimen is more advantageous in improving immune function over other regimens requires further comparative trials. The development of neuropathy in 25% of patients may limit the utility of this regimen, despite its potency.