Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1 persists in resting CD4؉ T cells, and low residual levels of free virus are found in the plasma. Limited characterization of this residual viremia has been done because of the low number of virions per sample. Using intensive sampling, we analyzed residual viremia and compared these viruses to latent proviruses in resting CD4 ؉ T cells in peripheral blood. For each patient, we found some viruses in the plasma that were identical to viruses in resting CD4 ؉ T cells by pol gene sequencing. However, in a majority of patients, the most common viruses in the plasma were rarely found in resting CD4 ؉ T cells even when the resting cell compartment was analyzed with assays that detect replication-competent viruses. Despite the large diversity of pol sequences in resting CD4 ؉ T cells, the residual viremia was dominated by a homogeneous population of viruses with identical pol sequences. In the most extensively studied case, a predominant plasma sequence was also found in analysis of the env gene, and linkage by long-distance reverse transcriptase PCR established that these predominant plasma sequences represented a single predominant plasma virus clone. The predominant plasma clones were released for months to years without evident sequence change. Thus, in some patients on antiretroviral therapy, the major mechanism for residual viremia involves prolonged production of a small number of viral clones without evident evolution, possibly by cells other than circulating CD4 ؉ T cells.Treatment of human immunodeficiency virus type 1 (HIV-1) infection with highly active antiretroviral therapy (HAART) reduces viremia to below the detection limit of ultrasensitive clinical assays (15,16,37). However, HIV-1 persists in resting CD4 ϩ T cells (6,8,9,12,51) and possibly other reservoirs (4, 58). The latent reservoir in resting CD4ϩ T cells has a long half-life (11,41,44,47,56) that will likely preclude virus eradication unless novel approaches (5, 24-28, 42) can purge latently infected cells.In patients on HAART, HIV-1 persistence is evidenced not only by the latent reservoir in resting CD4 ϩ T cells but also by free virus in the plasma (10,17,19,36,41,48,52). Free virions can be found with special methods, even in patients who do not have clinically detectable viremia (10,18,19,36,52). Given the short half-life of free virus (20,49), this residual viremia indicates active virus production. This virus production may reflect low-level ongoing replication that continues despite HAART (7,10,13,14,18,21,33,48,56) and/or release of virus from latently infected cells that become activated (19,22,34,48,55) or from other stable cellular reservoirs (4, 58). The characterization of residual viremia may provide a means for determining the importance of different mechanisms of viral persistence.Although the presence of free virus can be detected ...

SUMMARY An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing to high-risk exposure. ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection. After therapy was discontinued (when the child was 18 months of age), levels of plasma HIV-1 RNA, proviral DNA in peripheral-blood mononuclear cells, and HIV-1 antibodies, as assessed by means of clinical assays, remained undetectable in the child through 30 months of age. This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection.

A viral reservoir is a cell type or anatomical site in association with which a replication-competent form of the virus accumulates and persists with more stable kinetic properties than the main pool of actively replicating virus. This article reviews several cell types and anatomical sites proposed as potential reservoirs for HIV-1. It is now clear that HIV-1 persists in a small reservoir of latently infected resting memory CD4(+) T cells, which shows minimal decay even in patients on highly active antiretroviral therapy (HAART). The persistence of virus in this reservoir is consistent with the biology of these cells and the long-term persistence of immunologic memory. The viral replication that continues in patients on suppressive HAART may also contribute to the stability of this reservoir. There may be other reservoirs, but the latent reservoir in resting CD4(+) T cells appears to be sufficient to guarantee lifetime persistence of HIV-1 in the majority of patients on current HAART regimens, and unless new approaches are developed, eradication will not be possible. The clinical implications of this and other HIV-1 reservoirs are discussed.

REATMENT OF HUMAN IMMUNOdeficiency virus type 1 (HIV-1) infection with highly active antiretroviral therapy (HAART) can suppress viremia to below the limit of detection of available clinical assays. 1-3 The current goal of antiretroviral therapy is suppression of viremia to below 50 copies/mL of HIV-1 RNA, the limit of detection of the most sensitive available clinical assay. 4,5 Suppression to this level is necessary to prevent drug resistance, the major cause of treatment failure. 6,7 After achieving suppression, many patients experience intermittent episodes of detectable viremia ("blips"). 8-16 Blips may raise concern that resistance is developing and complicate management by increasing patient anxiety, triggering costly repeat measurements of viral load, and generating uncertainty re

Antiretroviral therapy is not curative. Given the challenges in providing life-long therapy to a global population of over 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

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Based on the samples that could be amplified, low-level viremia in children and adults receiving HAART with prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may result primarily from archival, pre-HAART virus, reflecting earlier treatment conditions, and does not appear to require development of new, HAART-selected mutations reflecting partial resistance to therapy. Low-level viremia below 50 copies/mL may represent less of a concern regarding impending drug failure of current HAART regimens. However, the archival drug-resistant virus may be relevant regarding future treatment strategies.

A diagnosis of neurocysticercosis should be considered in patients with seizures and radiologic evidence of cystic brain lesions, even in those who do not eat pork and who have not traveled to a country in which T. solium infection is endemic. Recent emigrants from countries in which T. solium infection is endemic should be screened for tapeworm infection in their stools before they are employed as housekeepers or food handlers.