Long-term symptomless HIV-1 infection in recipients of blood products from a single donor

Learmont, Jennifer; Tindall, Brett; Kaldor, John; Cooper, DA; Evans, Louise; Cunningham, Philip; Penny, Ronald; Cunningham, Anthony L.; Wells, J. Vivian

doi:10.1016/0140-6736(92)93281-q

Cited by 212 publications

(110 citation statements)

References 26 publications

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“…There has been recent interest in the phenomenon of longterm survival in HIV patients and in the explanation for the differences between such patients and rapid progressors. 21 ' 22 One suggestion put forward is that differences are due to a less virulent strain of HIV-1 22 but our data, as well as those of others, raise the possibility that it could also be due to decreased susceptibility in the host. In two recent reports the number of long-term survivors (10-15 years) infection varied from 5 to 15% of cohorts.…”

Section: Discussionmentioning

confidence: 49%

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

McNeil¹,

Yap

Gore

et al. 1996

QJM

128

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SummaryWe examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% Cl 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, Cl 0.1 -0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers ( p = 0 . 0 2 and p = 0.01, respectively); B27 was associated with slow loss of both markers ( p = 0 . 0 4 and p< 0.005).

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Section: Discussionmentioning

confidence: 49%

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

McNeil¹,

Yap

Gore

et al. 1996

QJM

128

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“…Human immunodeficiency virus type 1 (HIV-1) Nef is a 27-kDa myristoylated protein that has been shown to be an important determinant of viral pathogenesis, since individuals infected with viruses carrying defective Nef alleles progress very slowly to disease (6,15,37). Three well-described functions of Nef in cell culture systems are the enhancement of virion infectivity (11,45,57) and downmodulation of CD4 (1,24) and certain class I major histocompatibility complex (MHC) alleles (13,58).…”

mentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Nef Associates with Lipid Rafts To Downmodulate Cell Surface CD4 and Class I Major Histocompatibility Complex Expression and To Increase Viral Infectivity

Alexander

Bor

Ravichandran

et al. 2004

J Virol

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Lipid rafts are membrane microdomains that are functionally distinct from other membrane regions. We have shown that 10% of human immunodeficiency virus type 1 (HIV-1) Nef expressed in SupT1 cells is present in lipid rafts and that this represents virtually all of the membrane-associated Nef. To determine whether raft targeting, rather than simply membrane localization, has functional significance, we created a Nef fusion protein (LAT-Nef) containing the N-terminal 35 amino acids from LAT, a protein that is exclusively localized to rafts. Greater than 90% of the LAT-Nef protein was found in the raft fraction. In contrast, a mutated form, lacking two cysteine palmitoylation sites, showed less than 5% raft localization. Both proteins were equally expressed and targeted nearly exclusively to membranes. The LAT-Nef protein was more efficient than its nonraft mutant counterpart at downmodulating both cell surface CD4 and class I major histocompatibility complex (MHC) expression, as well as in enhancing first-round infectivity and being incorporated into virus particles. This demonstrates that targeting of Nef to lipid rafts is mechanistically important for all of these functions. Compared to wild-type Nef, LAT-Nef downmodulated class I MHC nearly as effectively as the wild-type Nef protein, but was only about 60% as effective for CD4 downmodulation and 30% as effective for infectivity enhancement. Since the LAT-Nef protein was found entirely in rafts while the wild-type Nef protein was distributed 10% in rafts and 90% in the soluble fraction, our results suggest that class I MHC downmodulation by Nef may be performed exclusively by raft-bound Nef. In contrast, CD4 downmodulation and infectivity enhancement may require a non-membrane-bound Nef component as well as the membrane-bound form.

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“…It is likely that new advances in the management of individuals with HIV infection will influence these distributions. Further, changes in the incubation period distribution could occur even in the absence of changes in available treatments and treatment uptake, due to the evolving distributions of new viral strains in HIV-infected persons [3,4]. It is therefore important to monitor whether there are changes in the incubation period distribution and, if so, the extent of those changes and factors associated with them.…”

Section: Background and Objectivesmentioning

confidence: 99%

The UK Register of HIV Seroconverters: methods and analytical issues

Beral¹,

Babiker²,

Brettle³

et al. 1996

Epidemiol. Infect.

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SummaryA Register of HIV-infected persons who have had a negative antibody test within 3 years of their first antibody positive test (seroconverters) is being set up in the UK to monitor the distribution of times from HIV seroconversion to AIDS (the incubation period) and to death. It will also provide a national resource for use by those designing studies in this group of individuals. Clinicians caring for HIV-positive persons in Genito-Urinary Medicine, Infectious Disease and other departments throughout the UK were asked to participate by providing information on eligible subjects. Most laboratories undertaking HIV antibody testing were also contacted and asked to provide the name of the attending clinician for all seroconverters identified through the HIV laboratory reporting systems of the PHLS Communicable Disease Surveillance Centre (CDSC) and the Scottish Centre for Infection and Environmental Health (SCIEH) and for any other seroconverters known to them but not identified by CDSC or SCIEH. Data items sought for the Register include: sex, ethnic group, probable route of HIV transmission, annual CD4 counts, details of therapy and prophylaxis prescribed, AIDS-defining events and vital status. Follow up information is collected annually. Wherever possible, all seroconverters known to a clinic have been identified, whether currently alive or dead, either from clinic records or laboratory reporting or both. The objective is to establish and update a complete register of seroconverters on a long-term basis to provide reliable estimates of the incubation period on which future projections of AIDS cases in the UK can be made.

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Long-term symptomless HIV-1 infection in recipients of blood products from a single donor

Cited by 212 publications

References 26 publications

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

Human Immunodeficiency Virus Type 1 Nef Associates with Lipid Rafts To Downmodulate Cell Surface CD4 and Class I Major Histocompatibility Complex Expression and To Increase Viral Infectivity

The UK Register of HIV Seroconverters: methods and analytical issues

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