Viral Load and Disease Progression in Infants Infected with Human Immunodeficiency Virus Type 1

William T. Shearer, Thomas C. Quinn, Philip LaRussa, Judy F. Lew, Lynne Mofenson, Susan Almy, Kenneth Rich, Edward Handelsman, Clemente Diaz, Marcello Pagano, Vincent Smeriglio, Leslie A. Kalish, for the Women and Infants Transmission Study Group

Abstract

Background. There are only limited data on human immunodeficiency virus type 1 (HIV-1) RNA in perinatally infected infants. Understanding the dynamics of HIV-1 infection and its relation to disease progression may help identify opportunities for effective antiviral treatment in infected infants.

Methods. We obtained plasma samples from 106 HIV-infected infants at birth; at 1, 2, 4, 6, 9, 12, 15, and 18 months of age; and subsequently every 6 months. HIV-1 RNA was assayed by means of a reverse-transcription polymerase chain reaction. The infants were born between 1990 and 1993, and only 21 percent of the infants' mothers received any treatment with zidovudine during pregnancy.

Results. Plasma HIV-1 RNA levels increased rapidly after birth, peaked at 1 to 2 months of age (median values at 1 and 2 months, 318,000 and 256,000 copies per milliliter, respectively), and then slowly declined to a median of 34,000 copies per milliliter at 24 months. Newborns with a first positive HIV-1 culture within 48 hours after birth had significantly higher HIV-1 RNA levels, although only during the first two months of life, than those with a first positive culture seven or more days after birth. Infants with a rapid progression of disease had higher peak HIV-1 RNA levels in the first two months of life than those without rapid progression (median value, 724,000 vs. 219,000 copies per milliliter; P = 0.006), as well as a higher geometric mean value during the first year of life (median value, 330,000 vs. 158,000 copies per milliliter; P = 0.001).

Conclusions. In perinatally infected infants, HIV-1 RNA levels are high and decline only slowly during the first two years of life. Infants with very high viral loads in the first months of life are at increased risk for a rapid progression of disease, which suggests that early treatment with antiretroviral agents may be indicated for these infants. (N Engl J Med 1997;336:1337-42.)

Source Information

From the Department of Pediatrics, Section of Allergy and Immunology, Baylor College of Medicine, Houston (W.T.S.); Johns Hopkins University, Baltimore (T.C.Q.); the National Institute of Allergy and Infectious Diseases, Bethesda, Md. (T.C.Q., J.F.L.); the Virology Department, Columbia-Presbyterian Hospital, New York (P.L.); the National Institute of Child Health and Human Development, Bethesda, Md. (L.M.); the New England Research Institutes, Watertown, Mass. (S.A., L.A.K.); the University of Illinois at Chicago, Chicago (K.R.); the State University of New York Health Science Center at Brooklyn, Brooklyn (E.H.); the University of Puerto Rico, San Juan (C.D.); the Department of Biostatistics, Harvard School of Public Health, Boston (M.P.); and the National Institute on Drug Abuse, Rockville, Md. (V.S.). Address reprint requests to Dr. Shearer at Texas Children's Hospital, 6621 Fannin St., MC 1-3291, Houston, TX 77030.

The members of the Women and Infants Transmission Study Group are listed in the Appendix.

Appendix

The Women and Infants Transmission Study Group included the following investigators and centers (with grants from the National Institutes of Health listed in parentheses): W. Shearer, C. Hanson, and N. Cooper -- Baylor College of Medicine, Houston (U01 AI 34840, AI 36211, and RR 00188); J. Pitt and A. Higgins -- Columbia-Presbyterian Hospital, New York (U01 AI 34842); K. Rich and D. Turpin -- University of Illinois at Chicago (U01 AI 34841); S. Landesman, H. Mendez, and G. Moroso -- State University of New York, Brooklyn (HD-8-2913 and R0-1-HD-25714); R. Tuomala, E. Cooper, and D. Mesthene -- Brigham and Women's Hospital, Boston (U01 AI 34856); C. Diaz and E. Pacheco-Acosta -- University of Puerto Rico, San Juan (U01 AI 34858); M.G. Fowler, J. Lew, and E. Matzen -- National Institute of Allergy and Infectious Diseases, Bethesda, Md.; A. Willoughby, D. Burns, J. Moye, J. Read, and L. Mofenson -- National Institute of Child Health and Human Development, Bethesda, Md.; V. Smeriglio and K. Davenny -- National Institute on Drug Abuse, Rockville, Md.; and S. McKinlay, L. Kalish, and K. Sherrieb -- New England Research Institutes, Watertown, Mass. (N01 AI 05072 and N01 AI 35161).