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We tested the hypothesis that a single nucleotide polymorphism (SNP) located near the interleukin-28B gene is associated with the control of hepatitis C virus and HIV-1 replication in elite controllers/suppressors. We show here that the protective genotype is not overrepresented in elite controllers/suppressors compared with HIV-1-seronegative patients and HIV-1-infected patients with viral loads more than 10 000 copies/ml. Thus, it appears that this SNP is not associated with the elite control of HIV-1 infection.

Elite controllers or suppressors (ES) are a group of HIV-1-infected individuals who maintain viral loads below the limit of detection of commercial assays for many years. The mechanisms responsible for this remarkable control are under intense study, with the hope of developing therapeutic vaccines effective against HIV-1. In this study, we addressed the question of the intrinsic susceptibility of ES CD4(+) T cells to infection. While we and others have previously shown that CD4(+) T cells from ES can be infected by HIV-1 isolates in vitro, these studies were confounded by exogenous activation and in vitro culture of CD4(+) T cells prior to infection. In order to avoid the changes in chemokine receptor expression that have been associated with such exogenous activation, we infected purified CD4(+) T cells directly after isolation from the peripheral blood of ES, viremic patients, and uninfected donors. We utilized a green fluorescent protein (GFP)-expressing proviral construct pseudotyped with CCR5-tropic or CXCR4-tropic envelope to compare viral entry using a fluorescence resonance energy transfer-based, single-round virus-cell fusion assay. The frequency of productive infection was also compared by assessing GFP expression. CD4(+) T cells from ES were as susceptible as or more susceptible than cells from viremic patients and uninfected donors to HIV-1 entry and productive infection. The results of this physiological study strongly suggest that differences in HIV-1 entry and infection of CD4(+) T cells alone cannot explain the elite control of viral replication.

We studied viral evolution in five human leukocyte antigen (HLA)-B*57 patients recently infected with HIV-1. Escape mutations in HLA-B*57-restricted Gag epitopes were present at study entry in all patients, but were not associated with significant increases in viremia. Conversely, no new escape mutations in HLA-B*57-restricted epitopes or known compensatory mutations were detected in patients who experienced significant increases in viremia. Thus, the development of escape mutations alone does not determine virologic outcome in recently infected HLA-B*57 patients.

HIV-1-specific antibodies can be detected in HIV-1-positive patients within weeks of primary infection. Rare cases have been reported of patients who are persistently seronegative despite evidence of HIV-1 infection. We present a retrospective review of the clinical, virologic and immunologic characteristics of 25 persistently seronegative patients whose cases have been published to date and postulate a biologic mechanism for this phenomenon.

HIV-1 infection usually results in high level of viral replication leading to a progressive decline of CD4+ T cells and eventually to full blown AIDS. Long term non-progressors (LTNPs) are patients who have stable CD4 counts for more than 5 years without antiretroviral therapy. Most of these patients have detectable levels of viremia and eventually will progress to AIDS. Elite controllers or suppressors (ES) represent a distinct subset of untreated patients who appear to be able to completely control viral replication. These patients maintain viral loads below the limit of detection of commercial assays for many years and generally do not show any clinical signs of disease progression. The mechanisms responsible for this remarkable control may lead to the design of effective HIV-1 vaccines.

In patients with progressive disease, untreated HIV-1 infection is characterized by high viral loads and decreasing CD4(+)T cell counts which lead to opportunistic infection and other AIDS-defining illness. A rare subset of patients termed 'elite controllers' (ECs) maintain control over viremia and often retain normal CD4(+)T cell levels without treatment with antiretroviral drugs. For the most part these patients are infected with replication-competent, fit virus. Factors such as strong, polyfunctional cytotoxic T lymphocyte (CTL) responses and retention of T cell proliferative ability appear to be important in control of HIV-1. Defining what enables ECs to control viral replication will aid in the development of effective vaccine and treatment regimens. This review will discuss differences between ECs and progressors while emphasizing recent findings on the immunological response of ECs to HIV-1.

We report a case of a patient infected with human immunodeficiency virus type 1 (HIV-1) for 20 years who has experienced CD4(+) T cell depletion in spite of maintaining undetectable viral loads. Our data suggest that immune activation can cause CD4(+) T cell depletion even when HIV-1 replication appears to be controlled by host factors.

Purpose of Review: HIV-1 infection is complicated by the presence of latently infected CD4 T cells as well as several anatomical reservoirs that present a barrier to eradication by current antiretroviral therapy. The early establishment of these reservoirs also presents a challenge to the development of preventive vaccines. This review will outline how HIV-1 evades the immune system and establishes latent infection, and will look at reasons why latently infected cells are not eradicated by the immune system. The HIV-specific immune responses in anatomical sanctuaries will be discussed., Recent Findings: HIV-specific immune responses have been studied in several anatomical reservoirs including the gut-associated lymphatic tissue that appears to be a major site of viral replication during primary infection., Summary: HIV-1 evades the immune system during primary infection. Anatomical sanctuaries are seeded in primary infection, and extensive replication occurs at these sites before the development of HIV-specific CD8 T-cell responses. These responses are not capable of clearing infection.