Natural History of Human Immunodeficiency Virus Type 1 Viremia after Seroconversion and Proximal to AIDS in a Large Cohort of Homosexual Men

Lyles, Robert H.; Muñoz, Álvaro; Yamashita, Traci E.; Bazmi, Holly; Detels, Roger; Rinaldo, Charles R.; Margolick, Joseph B.; Phair, John P.; Mellors, John W.

doi:10.1086/315339

Cited by 310 publications

(248 citation statements)

References 25 publications

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“…Studies suggest so far that the level of CD4 counts prior to HIV infection does not influence prognosis for those who get infected. Males from the Multicenter AIDS Cohort Study (MACS) with high CD4 counts prior to HIV infection had, compared to others, higher viral load, and steeper slope of CD4 counts decline in the early months following infection, so that there was no evidence for a beneficial effect of higher CD4 counts before infection (31). Also, it has been shown that females have higher CD4 counts than males at the time of HIV seroconversion, AIDS development, and death, without difference in survival compared to males (32).…”

Section: Discussionmentioning

confidence: 99%

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Abuye

Tsegaye²,

West

et al. 2005

J Clin Immunol

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To study the determinants of CD4% and CD4 counts among HIVnegative Ethiopians, and to identify factors susceptible to explain the low CD4 counts observed among Ethiopian subjects. Cohort studies among factory workers in Akaki and Wonji, Ethiopia. Clinical and laboratory examinations, including determination of HIV serological status and T-cell subsets, were performed during follow-up visits every six months. In addition, micronutrients (retinol, carotenoids, tocopherol, transferrin receptor, and selenium) plasma concentrations were determined in a subset of 38 HIV-positive and 121 HIV-negative participants. HIV-negative participants with at least one CD4 count measurement were 157 females in Akaki, 203 males in Akaki, and 712 males in Wonji. CD4 counts were independently and positively associated with body mass index (through an increase in lymphocyte counts), female gender (through an increase in CD4%), cigarette smoking (through an increase in CD4%), khat chewing (through an increase in both lymphocyte counts and CD4%), and Akaki study site (through a large increase in lymphocyte counts compensating a decrease in CD4%). Intestinal parasitic infections were not associated with CD4% or CD4 counts. Retinol, carotenoids, and α-tocopherol plasma concentrations decreased with HIV infection and advancing immunosuppression, but were not associated with CD4 counts among HIV-negative subjects. Low body mass index among Ethiopians may have contributed to their overall low CD4 counts. Other factors remain to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Abuye

Tsegaye²,

West

et al. 2005

J Clin Immunol

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“…This is surprising since the immunologic and virologic events that occur during the earliest stages of infection can have a strong impact on subsequent disease progression. [30][31][32] We therefore assessed the effects of T-cell activation and plasma HIV RNA levels on CD4 ϩ T-cell changes over time in a prospective cohort of acutely and recently HIV-infected adults. Our primary objective was to determine the relative contributions of viremia and T-cell activation to the rate of CD4 ϩ T-cell loss.…”

Section: Introductionmentioning

confidence: 99%

Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load

Deeks

Kitchen

Liu

et al. 2004

Blood

693

601

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Although generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation "set point" is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4 ؉ and CD8 ؉ T cells was measured longitudinally in 68 antiretroviral-untreated individuals and 83 antiretroviraltreated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8 ؉ T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10 000 copies/mL. Among untreated patients, the level of CD8 ؉ T-cell activation varied widely among individuals but often remained stable within a given individual. CD8 ؉ T-cell activation and plasma HIV RNA levels over time were independently associated with the rate of CD4 ؉ T-cell loss in untreated individuals. These data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4 ؉ T cells are lost over time. IntroductionUntreated HIV-1 infection is associated with a gradual loss of peripheral CD4 ϩ T cells. Although the direct cytopathic effect of HIV-1 on CD4 ϩ T cells almost certainly contributes to this gradual depletion, 1 most cells destined to die in vivo as a consequence of HIV infection are not productively infected with HIV. 2 This observation has led to the hypothesis that progressive CD4 ϩ T-cell depletion occurs due to indirect effects of viral replication. [3][4][5][6] The mechanism for these indirect effects of HIV replication on CD4 ϩ T-cell depletion is not understood.One widely accepted model postulates that HIV causes accelerated proliferation, expansion, and death of T cells, and that this heightened T-cell turnover eventually results in depletion or exhaustion of the regenerative capacity of the immune system. 4,5 Multiple studies have shown that HIV infection results in a state of high T-cell turnover (ie, the rates of T-cell proliferation and death are increased). For example, in vivo labeling of T cells indicates that HIV infection results in increased numbers of rapidly cycling CD4 ϩ and CD8 ϩ T cells. 7,8 These cells are primarily of memoryeffector phenotype, and are destined to proliferate and die rapidly. 9 The rate at which HIV recruits cells into this rapid turnover state is directly proportional to the level of viremia, 8 which in turn is directly related to the rate at which CD4 ϩ T cells are lost. 10 In the absence of antiretroviral treatment, markers of T-cell activation and T-cell turnover predict the rate of disease progression 11-14 and the rate of CD4 ϩ T-cell loss. 15 When antiretroviral therapy is initiated, the rate of T-cell turnover and the degree of generalized T-cell activation both decrease, suggest...

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“…This understanding is solidly underpinned by two long-standing observations. First, patients with higher viral loads progress to disease more quickly (2,3). Second, the possession of certain human leukocyte antigen (HLA) class I molecules (e.g., HLA B35) predisposes patients to rapid disease progression, whereas others (e.g., HLA B27 and HLA B58) endow them with a longer asymptomatic period (4)(5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Quantifiable cytotoxic T lymphocyte responses and HLA-related risk of progression to AIDS

Scherer

Frater

Oxenius

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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There are significant associations between possession of certain HLA class I alleles and rate of progression to AIDS. Immunological data provide an explanatory mechanism for this relationship. Patients with HLA types associated with rapid disease progression recognize a significantly smaller fraction of their known repertoire of viral epitopes than do patients with HLA types associated with slow progression. Population frequency of HLA types (or supertypes) and their capacity to elicit cytotoxic T lymphocyte responses are also negatively correlated. These data provide an immunological mechanism to explain HLA-related risk of progression to AIDS and emphasize the central role of viral evolution in the pathogenesis of HIV.

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Natural History of Human Immunodeficiency Virus Type 1 Viremia after Seroconversion and Proximal to AIDS in a Large Cohort of Homosexual Men

Cited by 310 publications

References 25 publications

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load

Quantifiable cytotoxic T lymphocyte responses and HLA-related risk of progression to AIDS

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