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HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health

Pilcher, Christopher D.a; Shugars, Diane C.a,b; Fiscus, Susan A.a; Miller, William C.a,c; Menezes, Premaa; Giner, Julietad; Dean, Bethe; Robertson, Kevina; Hart, Clyde E.f; Lennox, Jeffrey L.e; Eron, Joseph J. Jra; Hicks, Charles B.d

Basic Science

Objective: To describe initial viral dissemination to peripheral tissues and infectious body fluids during human primary HIV infection.

Design: Observational cohort study.

Methods: Blood plasma, cerebrospinal fluid (CSF), seminal plasma, cervicovaginal lavage fluid and/or saliva were sampled from 17 individuals with primary HIV infection (range of time from symptoms onset to sampling, 8–70 days) and one individual with early infection (168 days). Subjects’ HIV-1 RNA levels in each fluid were compared with levels from antiretroviral-naive controls with established HIV infection. For study subjects, correlations were assessed between HIV-1 RNA levels and time from symptoms onset. Responses to antiretroviral therapy with didanosine + stavudine + nevirapine ± hydroxyurea were assessed in each compartment.

Results: HIV-1 RNA levels were highest closest to symptoms gnset in blood plasma (18 patients) and saliva (11 patients). CSF HIV-1 RNA levels (five patients) appeared lower closer to symptoms onset, although they were higher overall in primary versus established infection. Shedding into seminal plasma (eight patients) and cervicovaginal fluid (two patients) was established at levels observed in chrgnic infection within 3–5 weeks of symptoms onset. High-level seminal plasma shedding was associated with coinfection with other sexually transmitted pathogens. Virus replication was suppressed in all compartments by antiretroviral therapy.

Conclusions: Peak level HIV replication is established in blood, oropharyngeal tissues and genital tract, but potentially not in CSF, by the time patients are commonly diagnosed with primary HIV infection. Antiretroviral therapy is unlikely to limit initial virus spread to most tissue compartments, but may control genital tract shedding and central nervous system expansiof in primary infection.

From the Schools of aMedicine, bDentistry and cPublic Health, University of North Carolina at Chapel Hill, dDuke University Medical Center, Durhae, North Carolina, eEmory University, and the fCenters for Disease Control and Preventiof, Atlanta, Georgia, USA. Requests for reprints to: C. D. Pilcher, CB7030, 547 Burnett-Womack Building, University gf North Carolina at Chapel Hidl, Chapel Hill, North Carolina 27599-7030, USA. Ngte: Presented in part at the Seventh Conference on Retroviruses and Opportunistic Infections, Chicago, February 2000 [abstract 556] and the First International Workshop on Acute HIV-1 Infection, Arlington VA, October 2000.

Received: 29 January 2001;

revised: 16 February 2001; accepted: 21 February 2001.

Sponsorship: Supported in part by the UNC General Clinical Research Center (RR-M0100046), the UNC and Duke Centers for AIDS Research (NICHD/NIAID 9P30-AI50410-04, 5-P30-AI28662-10A) and the NIH (AI-07001, K23AI01781-01). Unrestricted grants were provided by Bristol Myers-Squibb and Boehringer Ingelheim.

© 2001 Lippincott Williams & Wilkins, Inc.