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Early Therapy of Vertical HIV-1 Infection: Evidence for Cessation of Viral Replication and Absence of Virus-Specific Immunity K. LUZURIAGA*, M. MCMANUS, M. CATALINA, S. MAYACK, M. SHARKEY, M. STEVENSON, and J. L. SULLIVAN for the PACTG 356 Investigators.
Univ. of Massachusetts Med. Sch., Worcester Background: Plasma HIV-1 viral RNA suppression to below the limit of detection of currently available assays has been observed following potent combination antiretroviral therapy of individuals with established infection. However, latently infected cells persist, & detection of labile replication intermediates along with maintenance of HIV-1 specific immune responses suggests that these regimens do not completely halt viral replication.
Methods: We examined the impact of early combination antiretroviral therapy in 17 vertically infected infants who began therapy at age <3 mo and maintained plasma HIV-1 RNA <50 copies/ml for >48 wks. Regimens were ZDV/ddI/NVP (N=2), ZDV/3TC/NVP (N=3), ZDV/3TC/NVP/ABV (N=5), and d4T/3TC/NVP/NLF (N=7).
Results: Baseline plasma HIV-1 RNA range from 103.3 to 105.8 copies/ml (median 105.3). RNA was <400 by a median of 12 wks (range 0.5–16) and <50 by 24–68 wks. Intensive follow-up of these infants has continued through a median of 68 wks (range 48–212). CD4 count normalized or remained normal for age in all infants. All but 3 infants became HIV-1 seronegative after 48 wks of therapy. HIV-1 specific LPA and CTL responses have not been detected. Labile replication intermediates have not been detected in 8 infants studied after 48 wks of therapy.
Conclusion: Early combination antiviral therapy was associated with immune system preservation and led to a loss of plasma viremia, culturable virus, and labile episomal replication intermediates. Furthermore, these infants did not develop HIV-1 specific immune responses. These results suggest that early combination antiretroviral therapy may lead to cessation of viral replication and thus impact on the establishment of infection.
Key Words: acute infection, early antiretroviral therapy, vertical HIV-1 infection
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