Vigilancia Vih

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

review article
Medical Progress

Acute HIV-1 Infection
Myron S. Cohen, M.D., George M. Shaw, M.D., Ph.D., Andrew J. McMichael, M.B., B.Ch., Ph.D., and Barton F. Haynes, M.D. n 2009, the United Nations estimated that 33.2 million people worldwide were living with human immunodeficiency virus type 1 (HIV-1) infection and that 2.6million people had been newly infected.1 The need for effective HIV-1 prevention has never been greater. In this review, we address recent critical advances in our understanding of HIV-1 transmission and acute HIV-1 infection. Fourth-generation HIV-1 testing, now available worldwide,2,3 will allow the diagnosis of infection in many patients and may lead to new treatments and opportunities forprevention.

I

The HI V-1 T r a nsmission E v en t
More than 80% of adults infected with HIV-1 became infected through the exposure of mucosal surfaces to the virus; most of the remaining 20% were infected by percutaneous or intravenous inoculations.1 The risk of infection associated with different exposure routes varies,4 but no matter what the transmission route, the timing of the appearanceof viral and host markers of infection is generally uniform and follows an orderly pattern.5 Immediately after exposure and transmission, as HIV-1 is replicating in the mucosa, submucosa, and draining lymphoreticular tissues (Fig. 1),6,7 the virus cannot be detected in plasma; this so-called eclipse phase generally lasts 7 to 21 days.8,9 Once HIV-1 RNA reaches a concentration of 1 to 5 copies permilliliter in plasma, the virus can be detected with the use of sensitive qualitative methods of nucleic acid amplification10; at concentrations of 50 copies per milliliter, HIV-1 can be detected by means of quantitative clinical assays used to monitor viral load.11 The stages that define acute and early HIV-1 infection are characterized by the sequential appearance of viral markers and antibodiesin the blood (Fig. 2).5 More sensitive, fourth-generation tests, which detect both antigens and antibodies, shrink the virus-positive–antibody-negative window by about 5 days.12 Testing for viral RNA in plasma closes this gap by an additional 7 days. The characteristic appearance in the blood of viral markers of acute HIV-1 infection belies an extremely complicated and still poorly understoodseries of virus–host cell interactions in the tissues (Fig. 1).4,13 Given the varied routes of viral transmission — cervicovaginal, penile, rectal, oral, percutaneous, intravenous, in utero — and the distinctly different histologic features of these tissues, it is not surprising that several cell types are candidates for early infection. More is known about vaginal transmission than about otherroutes, and the study of human tissue explants14,15 and the Indian rhesus macaque model of vaginal transmission of the simian immunodeficiency virus (SIV)13,16-18 have been informative (Fig. 1). The preponderance of evidence implicates CD4 T cells and Langerhans’ cells as the first targets of the virus,14,15 but other dendritic cells may play an important accessory role.19 However, recent observationsof mucosally transmitted strains of HIV-1 reveal

From the Institute of Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill (M.S.C.), and the Duke Human Vaccine Institute, Duke University School of Medicine, Durham (B.F.H.) — both in North Carolina; the University of Alabama at Birmingham, Birmingham (G.M.S.); and the Weatherall Institute of MolecularMedicine and the National Institute for Health Research Biomedical Research Centre, Oxford University, Oxford, United Kingdom (A.J.M.). Address reprint requests to Dr. Cohen at 2031 Bioinformatics Bldg., 130 Mason Farm Rd., Chapel Hill, NC 27517, or at mscohen@med.unc.edu. N Engl J Med 2011;364:1943-54.
Copyright © 2011 Massachusetts Medical Society.

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may 19,...