RESUMEN
Agreement between assays for the detection of human herpesvirus 8 (HHV-8) antibodies has been limited. In part, this disagreement has been because assay calibration (i.e., differentiating positive from negative results) has not been done in a standardized fashion with reference to a wide spectrum of HHV-8-infected (true-positive) and HHV-8-uninfected (true-negative) persons. To describe the performance of an assay for HHV-8 antibodies more accurately, we used epidemiologically well-characterized subjects in conjunction with testing on two existing immunofluorescence assays for HHV-8 antibodies to define two groups: a group of 135 HHV-8-infected individuals (true positives), including Kaposi's sarcoma patients and those asymptomatically infected, and a group of 234 individuals with a high likelihood of being HHV-8 uninfected (true negatives). A new enzyme immunoassay (EIA), using lysed HHV-8 virion as the antigen target, was then developed. With the above true positives and true negatives as references, the sensitivity and specificity of the EIA associated with different cutoff values were determined. At the cutoff that maximized both sensitivity and specificity, sensitivity was 94% and specificity was 93%. When the EIA was used to test a separate validation group, a distribution of seropositivity that matched that predicted for the agent of Kaposi's sarcoma was observed: 55% of homosexual men were seropositive, versus 6% seropositivity in a group of children, women, and heterosexual men. It is proposed that the EIA has utility for large-scale use in a number of settings and that the calibration method described can be used for other assays, both to more accurately describe the performance of these assays and to permit more-valid interassay comparison.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8/inmunología , Técnicas para Inmunoenzimas/métodos , Niño , Femenino , Técnica del Anticuerpo Fluorescente , Infecciones por Herpesviridae/virología , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Although human herpesvirus 8 (HHV-8) has been suspected to be the etiologic agent of Kaposi's sarcoma, little is known about its seroprevalence in the population, its modes of transmission, and its natural history. METHODS: The San Francisco Men's Health Study, begun in 1984, is a study of a population-based sample of men in an area with a high incidence of human immunodeficiency virus (HIV) infection. We studied all 400 men infected at base line with HIV and a sample of 400 uninfected men. Base-line serum samples were assayed for antibodies to HHV-8 latency-associated nuclear antigen (anti-LANA). In addition to the seroprevalence and risk factors for anti-LANA seropositivity, we analyzed the time to the development of Kaposi's sarcoma. RESULTS: Anti-LANA antibodies were found in 223 of 593 men (37.6 percent) who reported any homosexual activity in the previous five years and in none of 195 exclusively heterosexual men. Anti-LANA seropositivity correlated with a history of sexually transmitted diseases and had a linear association with the number of male sexual-intercourse partners. Among the men who were infected with both HIV and HHV-8 at base line, the 10-year probability of Kaposi's sarcoma was 49.6 percent. Base-line anti-LANA seropositivity preceded and was independently associated with subsequent Kaposi's sarcoma, even after adjustment for CD4 cell counts and the number of homosexual partners. CONCLUSIONS: The prevalence of HHV-8 infection is high among homosexual men, correlates with the number of homosexual partners, and is temporally and independently associated with Kaposi's sarcoma. These observations are further evidence that HHV-8 has an etiologic role in Kaposi's sarcoma and is sexually transmitted among men.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/transmisión , Infecciones por Herpesviridae/transmisión , Herpesvirus Humano 8 , Sarcoma de Kaposi/virología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adulto , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Estudios de Seguimiento , Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8/inmunología , Herpesvirus Humano 8/aislamiento & purificación , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/inmunología , Factores de Riesgo , San Francisco/epidemiología , Sarcoma de Kaposi/epidemiología , Estudios Seroepidemiológicos , Parejas Sexuales , Enfermedades Virales de Transmisión Sexual/epidemiología , Factores de TiempoRESUMEN
To investigate the incidence of symptomatic primary human immunodeficiency virus type 1 (HIV-1) infection and its prognostic significance for HIV-1 disease progression, data for 328 homosexual men from four cohort studies were evaluated. Rates of diarrhea, fever, night sweats, cough, and fatigue prior to, during, and after seroconversion were compared by use of Poisson regression, and the prognostic significance of these symptoms was evaluated with survival methods. The incidence of all symptoms was elevated during seroconversion; however, only fever was associated with faster disease progression. Seven or more days of fever was reported by 13.8% of subjects; half of them developed AIDS within 6 years, whereas only one-fourth of the men without fever developed AIDS within 6 years. In addition, fever was the only symptom associated with shortened survival and increased CD4 cell loss. Persons experiencing prolonged periods of fever during seroconversion should therefore be considered for early treatment, including prophylaxis against opportunistic infections and combinations of antiretroviral drugs.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , VIH-1 , Homosexualidad Masculina , Recuento de Linfocito CD4 , Humanos , Incidencia , Masculino , PronósticoRESUMEN
OBJECTIVE: To identify appropriate criteria for characterizing HIV-infected nonprogressors. DESIGN: Five definitions were compared as follows: (1) last CD4 count > 500 x 10(6)/l; (2) two most recent CD4 counts > 500 x 10(6)/l; (3) calculated CD4 count based on linear regression > 500 x 10(6)/l; (4) CD4 slope > or = 0 with no antiretroviral use; (5) all CD4 counts > 500 x 10(6)/l, decline in CD4 slope < 5 cells per year, no antiretroviral use. PARTICIPANTS: Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion. MAIN OUTCOME MEASURES: Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded. RESULTS: Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1-3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1-3. None of the definitions classified the same subjects as nonprogressors at any timepoint. CONCLUSIONS: Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.