Mycoplasma species in rapid and slow HIV progressors.

We determined the relationship between the presence of Mycoplasma fermentans and Mycoplasma penetrans and the rate of progression of HIV-associated disease in a nested case-control study based on a cohort of 159 HIV-infected patients with different rates of disease progression. Study participants were divided into 3 progression groups: non-progressors who had been HIV-1 seropositive for at least 9 years and had remained asymptomatic with a CD4 cell count of > 500/mm3; slow progressors who had been HIV-1 seropositive for at least 9 years and whose CD4 cell count had fallen below 500 cells, and who had developed symptomatic disease or AIDS; and rapid progressors who had developed AIDS within 5 years of HIV infection. Peripheral blood mononuclear cells (PBMCs) were collected at enrollment and examined by mycoplasma polymerase chain reaction (PCR) assays.

Partial "repair" of defective NEF genes in a long-term nonprogressor with human immunodeficiency virus type 1 infection.

A 36-bp deletion close to the 5' end of NEF that impaired Nef function was found in a long-term nonprogressor with human immunodeficiency virus type 1 (HIV-1) infection. Forms containing an adjacent duplication of 33 bp were also frequently observed. The duplication showed no homology to the deleted region but restored the overall length of the first variable loop of Nef.

Cytotoxic T lymphocytes and viral evolution in primary HIV-1 infection.

Efforts to develop immune-based therapies for HIV infection have been impeded by incomplete definition of the immunological correlates of protection. Despite many precedents demonstrating that CD8(+) cytotoxic T lymphocytes are key mediators of protective anti-viral immunity in non-human animal models, direct evidence that these effector cells control viral replication in HIV-1 infection has remained elusive. The first part of this paper describes a detailed immunological and genetic study founded on evolutionary considerations.

Decreased morbidity and use of hospital services in English HIV-infected individuals with increased uptake of anti-retroviral therapy 1996-1997. National Prospective Monitoring System Steering Group.

Objective: To investigate the relationship between changing morbidity patterns, the use of hospital services by HIV-infected patients and the uptake of antiretroviral therapy (ART) in England.

Design: Prospective serial cross-sectional analyses based on data collected through the National Prospective Monitoring System (NPMS), a multi-centre prospective monitoring system.

Setting: HIV-infected patients seen in 10 clinics, five London and five non-London, during the three semesters, 1 January 1996 to 30 June 1997.

Acid-alcohol fast bacilli in sputa of HIV-infected patients.

We identified 34 HIV-infected patients with sputum smear positive for acid-alcohol fast bacilli (AAFB) to determine any factors predictive of subsequent species identification. There were 20 cases of Mycobacterium tuberculosis (MTB), 9 cases of Mycobacterium avium-intracellulare (MAI), 3 cases of Mycobacterium kansasii and one each of Mycobacterium malmoense and Mycobacterium fortuitum. Factors associated with isolation of MAI were lower CD4 cell count, a higher incidence of previous AIDS diagnosis, a history of dyspnoea and a normal chest X-ray.

Chemokine receptor polymorphisms and human immunodeficiency virus disease progression.

The role of polymorphisms in genes encoding chemokines and their receptors (CCR2B, SDF-1, and the promoter region of CCR5) in human immunodeficiency virus (HIV) disease progression was studied in 132 white HIV type 1 (HIV-1)-infected participants from a United Kingdom cohort study. Genotyping was done by use of amplification refractory mutation system-polymerase chain reaction with sequence-specific primers, and Cox proportional hazards models were used to examine the impact of polymorphisms on time to a CD4 cell count <200x106/L and to CDC stage IV disease. The results confirm a significant association of the CCR2B-64I mutant genotype with slower progression to a CD4 count <200 (hazards ratio [HR], 0.

Sequence variations in human immunodeficiency virus type 1 Nef are associated with different stages of disease.

nef alleles derived from a large number of individuals infected with human immunodeficiency virus type 1 (HIV-1) were analyzed to investigate the frequency of disrupted nef genes and to elucidate whether specific amino acid substitutions in Nef are associated with different stages of disease. We confirm that deletions or gross abnormalities in nef are rarely present. However, a comparison of Nef consensus sequences derived from 41 long-term nonprogressors and from 50 individuals with progressive HIV-1 infection revealed that specific variations are associated with different stages of infection.

The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs.

Objective: The aim of the study was to measure the use and estimate the cost of HIV service provision in England.

Design And Setting: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996.

Are HIV-infected patients with rapid CD4 cell decline a subgroup who benefit from early antiretroviral therapy?

We have developed a model to determine whether asymptomatic HIV-infected individuals who have a rapid CD4 cell decline are a subgroup who might benefit from early antiretroviral therapy. Data were obtained from a subgroup of participants in the Concorde and EACG020 trials, two randomized, double-blind, comparative trials of immediate (IMM) versus deferred (DEF) zidovudine therapy in asymptomatic HIV-infected individuals. The subgroup comprised 297 patients (IMM = 154, DEF = 143) who had at least one CD4 cell count before and after randomization.

HLA-Cw*0602 and HIV-associated psoriasis.

The aetiopathogenesis of psoriasis is unknown, but genetic and environmental factors may be involved. Psoriasis may not be one disease but a cutaneous inflammatory reaction pattern consequent upon several different independent or related stimuli in susceptible individuals. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4 vs.

Bronchopulmonary Kaposi's sarcoma in 106 HIV-1 infected patients.

The objectives of this study were to describe the clinical and radiological features at presentation, and the natural history of HIV-related bronchopulmonary Kaposi's sarcoma. A retrospective review of medical records and chest radiographs was performed in 106 HIV-infected homosexual men with bronchopulmonary Kaposi's sarcoma diagnosed at bronchoscopy between September 1988 and November 1994. The majority of patients had evidence of advanced HIV disease at diagnosis (median CD4 cell count was 15 x 10(6)/l, range 0-288), and 93% had had a diagnosis of cutaneous Kaposi's sarcoma for a median duration of 11 months prior to diagnosis of their bronchopulmonary disease.

Association between a defective CCR-5 gene and progression to disease in HIV infection.

We measured the effect(s) of CCR-5 genotype on disease progression by studying the frequency of a defective CCR-5 delta32 allele within a cohort of long-term infected individuals. An elevated frequency of CCR-5 delta32 heterozygotes within the cohort compared with a control population of blood donors was observed. An association between progression rate and CCR-5 delta32 heterozygosity was observed.

1H MR spectroscopy of the brain in HIV-1-seropositive subjects: evidence for diffuse metabolic abnormalities.

Purpose: To analyze brain metabolite changes in HIV-1-seropositive subjects in order to define whether the neuronal impairment is a localized or more diffuse process.

Materials And Methods: 15 patients and 18 volunteers underwent multivoxel proton magnetic resonance (MR) spectroscopy at 1.5T.

Research potentials and pitfalls in the use of an HIV clinical database: Chelsea and Westminster Hospital.

This article summarizes the various problems and pitfalls in using clinical databases for epidemiologic research, with particular reference to an HIV clinical database. The combined population of HIV-infected individuals attending the Chelsea and Westminster Hospital, the Charing Cross Hospital, and the Victoria Clinic in London is the largest cohort of HIV-positive individuals in the U.K.

The incidence of AIDS-defining illnesses in 4883 patients with human immunodeficiency virus infection. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

Background: Acquired immunodeficiency syndrome (AIDS)-defining illnesses are known to occur at different levels of immunosuppression, and the incidence of diagnoses may also vary according to the CD4 lymphocyte count strata. Information about the incidence of disease at different levels of immunosuppression would help clinicians monitoring patients and would allow prophylaxis to be targeted at the most appropriate population.

Methods: Between 1982 and July 1995, 4883 patients testing positive for the human immunodeficiency virus were seen at either the Royal Free or Chelsea and Westminster Hospitals in London, England.

Neutralization of primary and T-cell line adapted isolates of human immunodeficiency virus type 1: role of V3-specific antibodies.

The role of the third variable domain (V3) of gp120 in the neutralization of primary and T-cell line adapted (TCLA) strains of human immunodeficiency virus type 1 (HIV-1) by serum from HIV-1-infected individuals was investigated. A primary virus isolate, M2424/4, when adapted to H9 cells, was more sensitive to neutralization on MT2 cells than the same stock passaged in PBMC. Neutralization of the PBMC-passaged stock by V3-specific MAbs was abrogated by addition of V3 (MN) peptide.

Relationship between CD4 count and CD4% in HIV-infected people.

Objective: To describe the relationship between absolute CD4 count and CD4%, and the influence on this of gender, risk group, age, a diagnosis of AIDS, use of zidovudine (ZDV) therapy and PCP prophylaxis.

Methods: 9203 paired serial measurements of CD4 count and CD4% on 1017 initially AIDS-free and ZDV-naive HIV positive patients from a London-based cohort were available for analysis. Multi-level regression procedures were used on log-transformed data to relate values of CD4 count to a given level of CD4%.

CD4 cell counts of 200 x 10(6)/1 or below in natural history studies and surveillance: is one enough or are two better?

A retrospective cohort study was performed to examine the extent and clinical significance of misclassification associated with using the current United States AIDS case defining category of an initial CD4 count < or = 200 cells x 10(6)/l (< or = 200) compared with a definition requiring two consecutive counts below this level. The main outcomes examined were the probability of subsequent CD4 counts > 200 x 10(6)/l (> 200) and progression times to AIDS and death. Of the 2025 predominantly male homosexual HIV-positive patients attending two hospital based HIV clinics with initial CD4 cell counts < or = 200, 1524 (75%) subsequently had consecutive counts < or = 200, but only half did so at the next CD4 count.

Antiretroviral therapies in HIV-1 infection.

Recent progress in our understanding of the viral dynamics and immunobiology of HIV infection, coupled with the introduction of a new generation of antiretroviral agents, has led to significant advances in the medical management of HIV infection. Eleven antiretroviral drugs are currently licensed in the United States, and eight are licensed in Europe. These include the nucleoside reverse transcriptase inhibitors (AZT, ddI, ddC, 3TC and d4T); the non-nucleoside reverse transcriptase inhibitors (nevirapine and delavirdine) and the protease inhibitors (saquinavir, indinavir and ritonavir).