Markers of health status in an HTLV-I-positive cohort.

The health effects of chronic human T-cell lymphotropic virus type I (HTLV-I) infection were examined in a cohort of Japanese men who had emigrated from Okinawa, Japan, and had been participants in a prospective study in Hawaii since 1965. In the present follow-up study carried out in 1987-1988, various health indicators were measured in the subjects, whose mean age was 72.5 years. Participation rates were lower in the HTLV-I seropositives than in the seronegatives (46.7% vs. 76.0%) in the > or = 75-year age group. Lack of participation was significantly correlated with a high HTLV-I antibody titer. Among the participants, seropositive subjects were significantly more likely than the seronegatives to have lymphocytopenia (32.7% vs. 17.7%) and mild anemia (25.5% vs. 14.1%) after adjustment for age and socioeconomic status. The seropositives also had a higher frequency of acupuncture therapy (age-adjusted odds ratios were 2.1 and 4.2 for 1-5 treatments and > or = 6 treatments, respectively). Proportions of subjects who had been hospitalized at least twice were higher among the seropositives in the oldest age groups, 70-74 years and > or = 75 years, but not in those aged 65-69 years. Although specific disease conditions were not identified in this study, hematologic data, treatment histories, and the correlation between participation status and HTLV-I antibody titers suggest that chronic HTLV-I infection may be associated with as yet undefined adverse health effects, particularly in older age groups.

Predictors of the risk of development of acquired immunodeficiency syndrome within 24 months among gay men seropositive for human immunodeficiency virus type 1: a report from the Multicenter AIDS Cohort Study.

The natural history of infection with human immunodeficiency virus type 1 (HIV-1) is characterized by a relentless decline in CD4-positive lymphocytes and the ultimate development of acquired immunodeficiency syndrome (AIDS). However, variables other than the CD4-positive lymphocyte level contribute to the measurement of risk for AIDS and can be used as predictors of AIDS onset. This study was undertaken to identify factors that, independently of the CD4-positive lymphocyte level, would predict the risk of AIDS over 24 months in a cohort of HIV-1 seropositive homosexual men receiving no antiretroviral therapy. Demographic, clinical, and laboratory data from 1,325 white, HIV-1 seropositive participants in the Multicenter AIDS Cohort Study who have been studied for 4 years were analyzed with univariate and multivariate methods. To control for stage of infection, the baseline percentage of CD4-positive lymphocytes (a known marker of disease progression), and the decline of CD4-positive cells during the first 6 months of observation were used as continuous variables. The variables that were independently associated with an increased risk of developing AIDS were: low baseline CD4 percentage, decline in the CD4 percentage during the first 6 months of follow-up, the presence of serum immunoglobulin A at baseline, decrease in hemoglobin during the first 6 months of follow-up, incident fatigue, and the interaction of decline in the CD4 percentage and incident thrush. While low CD4 percentage and other variables have been previously described as prognostic markers, decline in the CD4 percentage and the interaction of that decline and incident thrush have not previously been described as being of prognostic importance. These variables and the analytic method for estimating prognosis may prove useful for selecting and evaluating antiretroviral therapy, instituting prophylactic measures against certain opportunistic infections, and recruitment into clinical trials. Because study participants received no antiretroviral prophylaxis during the period under analysis, the method could be used to estimate the prognosis for those receiving investigational treatment were they to remain untreated, effectively making any participant in a clinical trial his own untreated control.

Declining seroprevalence and transmission of HTLV-I in Japanese families who immigrated to Hawaii.

This study examined the seroprevalence and transmission of human T cell lymphotropic virus type I (HTLV-I) in Japanese families who originated in Okinawa, an area in which HTLV-I is endemic, and who were currently residing in Hawaii, a nonendemic area. Among a cohort of Japanese men whose sera were collected in Hawaii in 1967-1975, those of Okinawan ancestry had an HTLV-I seroprevalence of 11.4%. This study, conducted in 1987-1988, sampled 142 index subjects from this male cohort and tested them along with their wives, children, and spouses of the children for HTLV-I antibodies. Seropositivity in their wives was 11.4% and 41.2% among the seronegative and seropositive index subjects, respectively; seropositivity also increased from 29.4% to 35.3% to 58.8% with the husbands' increasing antibody levels by tertiles. Elevated antibody levels may be a marker for infectivity, which is associated with more efficient sexual transmission of HTLV-I. The age-adjusted odds ratio for the association of seropositivity between husband and wife, however, was four times lower than that reported among native Okinawans. In addition, a substantially low seroprevalence (1.3%) was found among their offspring. The decline in HTLV-I transmission in this migrant population may be due to low infectivity in the parent generation who live in a nonendemic environment, increasing numbers of offspring marrying outside of the Okinawan community, and improved living circumstances.

Epstein-Barr virus antibody patterns preceding the diagnosis of non-Hodgkin's lymphoma.

Immunosuppressed patients who develop non-Hodgkin's lymphoma (NHL) have abnormal antibody responses against the Epstein-Barr virus (EBV) prior to the diagnosis of malignancy. To see if this is also true of "spontaneous" cases in the general population, we undertook a collaborative serologic case-control study. From 4 serum banks containing specimens from over 240,000 persons, 104 subjects were identified for whom a blood specimen had been stored an average of 63 months before diagnosis of NHL, and 259 controls matched for age, sex, ethnic group and date of serum collection. The relative risks (RR) for subsequent development of NHL associated with elevated levels of IgG and IgM antibodies against viral capsid antigen were 2.5 (95% confidence interval = 1.1-5.7) and 3.2 (1.3-7.5), respectively; these associations increased with age at diagnosis. For the nuclear antigen, the distribution of titers for cases was more restricted than that of controls, with fewer cases having either elevated or low titers, RR = 0.5 (0.2-1.4) and 0.5 (0.2-1.2), respectively. Cases had significantly lower antibody titers against the cytomegalovirus, RR = 0.4 (0.2-0.9). These findings suggest that, at least for some patients, NHL is preceded by an enhanced level of endogenous immunosuppression with resultant EBV activation. This observation supports the role of EBV either directly in the development of NHL or as a primary marker of immune dysfunction.

Epstein-Barr virus antibody patterns preceding the diagnosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) patients have elevated IgG and IgA antibody titers against the Epstein-Barr viral capsid antigen (VCA) and the diffuse component of the early antigen complex (EA-D) at diagnosis. Several studies have implied that the presence of anti-VCA-IgA can be used as a screening marker for early NPC. To evaluate this further, we undertook a serologic case-control study based on four serum banks which together had specimens from over 240,000 persons. Seven cases of undifferentiated or poorly differentiated NPC were diagnosed in the period after serum collection ranging from 26 months to 154 months. Two controls per case matched on serum bank, age, sex, race, and date of serum collection were selected by a predetermined random process. For anti-VCA-IgG, the geometric mean titer for cases (88.3) was significantly higher than that for controls (75.5, P less than 0.05). The difference was greatest among the Asian patients. No significant differences were found for anti-VCA-IgA, anti-EA-D, and anti-EA-R or anti-EBNA. No time effects were evident when titers were plotted against time of blood collection preceding diagnosis. Our results do not suggest EBV activation in the period preceding NPC diagnosis, nor that detectable IgA antibody against VCA is a marker for early disease.

Human immunodeficiency virus infection in women attending an inner-city prenatal clinic: ineffectiveness of targeted screening.

Women attending an inner-city prenatal clinic between February, 1987 and August, 1988 completed a questionnaire to assess risk factors for human immunodeficiency virus (HIV) infection. Women with risk factors were offered HIV testing. Testing was available to women without risk factors upon their request. Stored sera were obtained for anonymous HIV testing on patients not consenting for testing. Overall, 30 of 622 women (5%) tested HIV positive. Ten per cent of women acknowledging risk factors were seropositive vs 3% denying risk factors (P less than .001). Intravenous (IV) drug use was reported in 40% of seropositive women. However, 47% (14/30) of HIV seropositive women denied risk factors for infection. Limiting prenatal HIV screening to women acknowledging risk factors may fail to identify a substantial number of infected women. Screening for HIV infection, counseling, and education on risk reduction should be offered to all pregnant women.

Risk factors for preterm premature rupture of fetal membranes: a multicenter case-control study.

To assess the association between women with preterm premature rupture of membranes and 41 potential risk factors, we conducted a case-control study in six United States tertiary perinatal centers. The study involved completion of a comprehensive questionnaire for 341 women with preterm premature rupture of membranes in singleton pregnancies from 20 to 36 weeks' gestation and 253 control women matched for maternal age, gestational age, parity, clinic or private patient status, and previous vaginal or cesarean delivery. Univariate analysis revealed 11 variables associated with a significantly (p less than 0.05) increased risk of preterm premature rupture of membranes. After multiple logistic regression analysis, three variables remained in the model as independent risk factors: antepartum vaginal bleeding in more than one trimester (odds ratio 7.4; 95% confidence interval, 2.2, 25.6), current cigarette smoking (odds ratio, 2.1; 95% confidence interval, 1.4, 3.1), and previous preterm delivery (odds ratio, 2.5; 95% confidence interval, 1.4, 2.5). Cessation of cigarette smoking by pregnant women may reduce the risk of preterm premature rupture of membranes. Further study is necessary to determine the nature of the relationship between antepartum vaginal bleeding and preterm premature rupture of membranes.

Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer.

We investigated the associations of serum retinol, the carotenoids beta-carotene and lycopene, and tocopherol (vitamin E) with the risk of prostate cancer in a nested case-control study. For the study, serum obtained in 1974 from 25,802 persons in Washington County, MD, was used. Serum levels of the nutrients in 103 men who developed prostate cancer during the subsequent 13 years were compared with levels in 103 control subjects matched for age and race. Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer. We analyzed data on the distribution of serum retinol by quartiles, using the lowest quartile as the reference value. Odds ratios were 0.67, 0.39, and 0.40 for the second, third, and highest quartiles, respectively.

Seasonal and annual variation of antibody to HIV-1 among male inmates entering Maryland prisons: update.

Previous serosurveys of antibody to HIV-1 among incoming male inmates in Maryland between April and June of 1985, 1986 and 1987 have shown a prevalence of 7.0, 7.7 and 7.0%, respectively, with stability persisting after multivariate adjustment. To investigate seasonality and update annual trends, excess sera were obtained from incoming male inmates between August 1987 and August 1988. Correctional personnel also provided demographic variables of age, race, offense, category, and jurisdiction. Once rendered anonymous, specimens were assayed for antibody to HIV-1 using enzyme-linked immunosorbent assay and Western blot. For the 12-month study period, 415 (7.9%) of 5262 consecutive male entrants were seropositive. On univariate and multivariate analyses, no significant change in seroprevalence or risk by subgroup was noted by month or season. For data from April to June 1988, 113 (8.1%) of 1398 consecutive entrants demonstrated anti-HIV-1; seropositivity was associated with age greater than 25 years, Black race, and Baltimore jurisdiction. No significant change was found over time in seroprevalence or risk of HIV-1 infection by subgroup in multivariate analysis combining data for 1985-1988. These data provide additional evidence to suggest stability of HIV-1 seroprevalence in Maryland male prison entrants.

Decreasing seroprevalence of human immunodeficiency virus type 1 in a regional blood donor population.

Blood banks have intensified their efforts to discourage donations from individuals at risk for the human immunodeficiency virus (HIV-1). Since the onset of HIV-1 donor screening in April 1985, a marked reduction in seroprevalence has been seen at the authors' institutions: from 51 cases per 100,000 donors in 1985 to 13 per 100,000 in the first 6 months of 1988. Data from 3.5 years have been analyzed for temporal trends in the association of HIV-1 seroprevalence with donation site (urban vs. non-urban) and donor gender. The association of HIV-1 seropositivity with an urban donation site decreased through 1987 as the urban-to-nonurban donation odds ratio declined from 6.48 in 1985 to 2.54 in 1987. Despite this decrease, both men and women who donated in urban areas had a significantly higher seroprevalence than those in nonurban areas. Male donors had a higher overall HIV-1 seroprevalence than female donors. However, the male-to-female odds ratio declined from 2.94 in 1985 to 1.96 in 1988, and male gender was no longer significantly associated with HIV-1 seropositivity. This change in the donor profile appears to reflect declining numbers of seropositive men who acknowledge risk factors and greater numbers of women with no identified risks for HIV-1. This study documents a dramatic decrease in HIV-1-seropositive donors and suggests that the deferral of high-risk individuals has become increasingly successful.

Incidence of Kaposi's sarcoma in a cohort of homosexual men infected with the human immunodeficiency virus type 1. The Multicenter AIDS Cohort Study Group.

Longitudinal data on 2,125 participants in the Multicenter AIDS Cohort Study (MACS) with documented antibodies to the human immunodeficiency virus type 1 (HIV-1) were used to examine the incidence of acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) over time and to determine if sexual practices and hematologic variables prior to diagnosis differed for participants who develop KS vs. non-KS AIDS (NKS). In the first 4 years of the study, 84 seropositive men were observed to develop KS and 307 presented with an AIDS diagnosis other than KS. A systematic trend in the incidence of KS over time was not apparent in this population. The number of anal-receptive intercourse partners prior to diagnosis declined in a similar fashion for both AIDS groups. Although the number of partners with whom the men performed rimming decreased prior to diagnosis for both AIDS groups, a greater proportion of the KS AIDS group had performed this activity with multiple partners than had the non-KS AIDS group. Furthermore, history of oral gonorrhea was significantly (p = 0.027) more prevalent in the KS group. In addition, the KS AIDS group had lower cytomegalovirus antibody levels prior to diagnosis and higher levels of total immunoglobulin G. The groups did not differ with respect to baseline hematological measures, temporal trends in helper and suppressor T cells, or hepatitis B surface antigen or antibody. Given this profile of factors associated with the occurrence of KS, an infectious agent, in addition to HIV-1, is plausible as a proposed cofactor in the development of KS.

HIV-1, sexual practices, and contact with foreigners in homosexual men in Colombia, South America.

From October 1985 to November 1987, a sample of 294 Colombian homosexual men volunteered to answer a questionnaire on sexual practices and consented to HIV-1 testing. Testing for HIV-1 was performed using an ELISA and those positive were confirmed with envelope- and core-specific ELISAs. Statistical methods for data analysis included Mantel-Haenszel methods on contingency tables. The overall seropositivity rate was 21.1%. Subjects who reported a receptive role (either as predominantly receptive or as mixed receptive-insertive intercourse) had a seropositivity rate of 23.7%, which was significantly higher than the 10.3% found in those reporting predominantly insertive intercourse (RR = 2.30, 95% C.I. = 1.16-4.57). For subjects reporting receptive intercourse, sexual contact with foreign visitors was a significant risk factor for HIV-1 infection (RR = 1.84, 95% C.I. = 1.13-3.00). Factors of borderline significance included having had more than ten homosexual partners in the preceding year (RR = 1.53) and a history of international travel (RR = 1.43). These associations did not hold for those reporting predominantly insertive intercourse. The data indicate the need to monitor the spread of HIV-1 at the international level and provide information on subgroups of high transmission rates.

The effect of fresh lymphocytes on increased sensitivity of HIV-1 isolation: a multicenter study.

A multicenter study was undertaken to determine the sensitivity and reproducibility of markers for human immunodeficiency virus type 1 (HIV-1) viral growth and the effect of various preparations of lymphocytes on the sensitivity of standard and routinely used procedures for HIV-1 isolation. In phase 1, cocultivated culture supernatants obtained from 10 HIV-1 cultures were transported to three Multicenter AIDS Cohort Study (MACS) Virology Laboratories. Three commercial HIV-p24 antigen capture (AC) tests and two reverse transcriptase (RT) assays were used to ascertain the replication of HIV-1. The Du Pont and Abbott AC assays were found to be most sensitive (85-100%), and the RT assay with 24-h incubation period had comparable sensitivity (75-100%). In phase II, the sensitivity of standard cocultivation procedure for HIV-1 isolation was compared using freshly phytohemagglutinin-P (PHA-P)-stimulated, stimulated-frozen, and frozen-thawed and then stimulated normal human peripheral blood mononuclear cells (PBMCs) as cocultivating cells. Blood samples from 13 HIV-1 infected individuals with various CD4+ cell counts were cocultivated in each of the three MACS laboratories using one of the aforementioned normal PBMCs. The PHA-P-stimulated fresh normal PBMC showed a maximum isolation rate of 100% (13 of 13) with an average of 8 days to positivity. This rate of isolation was significantly greater than other rates using any one of the other PBMC preparations. These findings demonstrated that the use of freshly PHA-P stimulated PBMCs maximized HIV-1 isolation from blood when a sensitive HIV-1 p24 AC assay or RT assay with overnight incubation is employed for the detection of HIV in culture supernatant.

Acquired immunodeficiency syndrome (AIDS)-free time after human immunodeficiency virus type 1 (HIV-1) seroconversion in homosexual men. Multicenter AIDS Cohort Study Group.

To estimate the time interval between human immunodeficiency virus type 1 (HIV-1) seroconversion and acquired immunodeficiency syndrome (AIDS) diagnosis in homosexual men, prospective incident cohorts are difficult to obtain and, if assembled, provide few events owing to the long incubation time. Although seroprevalent cohorts are numerous in size and events, the information is limited due to the unknown times since seroconversion. To combine the information provided by 1,628 seroprevalent men (304 AIDS cases) and 233 seroconverters (12 AIDS cases) being followed in a multicenter study since 1984, the postseroconversion changes in hematologic variables occurring in the incident cohort were used to develop a model that allowed for the imputation of the unknown times since seroconversion for the seroprevalent cohort. Nonparametric life table methods incorporating truncation and censoring were applied for the estimation of the probability distribution of the AIDS-free time after seroconversion. The precision of the estimates was evaluated using bootstrap methods. The analysis suggested that AIDS is unlikely (less than 0.5%) in the first year; 78% of seropositive homosexual men remain AIDS-free 60 months after seroconversion; and the AIDS incidence increases for months 12-36 and levels off at 38 per 1,000 person-semesters for months 42-60. The nonparametric estimate of the incidence rate suggests a median AIDS-free time of 11 years, which is longer than previous estimates based on parametric models.

Seroepidemiology of hepatitis B virus infection in the United States. 1976 to 1980.

The prevalence of hepatitis B virus (HBV) infection was determined using sera from persons participating in the second National Health and Nutrition Examination Survey, conducted from 1976 to 1980. Of 14,488 scientifically selected participants aged 12 to 74, 821 had evidence of past or present infection with HBV. In the white population, the weighted estimate of hepatitis B infection was 3.2 percent (95 percent confidence interval, 3.1 to 4.2). A steady increase with age was seen; by ages 65 to 74, the prevalence was 6.9 percent (95 percent confidence interval, 5.2 to 8.5). In the black population, the overall weighted estimate of prevalence was 13.7 percent (95 percent confidence interval, 11.6 to 15.8). In this racial group, there was a dramatic increase with age, with the oldest age groups having a prevalence of 39.6 percent (95 percent confidence interval, 29.1 to 50.0). In both racial groups, there was a low prevalence of infection in young children that began to rise between ages 12 and 18. In a multivariate analysis of factors associated with infection, there was an interaction of race with age; therefore, the odds ratio for race is presented for four ages. This ratio ranged from 3.0 (95 percent confidence interval, 1.8 to 4.2) for a 15-year-old to 8.2 (95 percent confidence interval, 6.5 to 10.3) for a 70-year-old. These relative odds estimates were not substantially affected by adjustment for the available information on risk factors for HBV infection. The results of this study in a representative sample of the United States population show that adult black Americans are at high risk for hepatitis B infection. Other independent predictors of HBV positivity include male sex; residing in the South, Northeast, or West; residing in a city of 250,000 or more people; serving in the armed forces; living below the poverty level; and having a positive treponemal test for syphilis. These data suggest that the immunization practices for controlling this disease should be re-examined.

Performance of serological assays for early detection of human immunodeficiency virus type 1 seroconversion.

Early detection of sexually transmitted human immunodeficiency virus type 1 (HIV-1) infection was investigated in newly infected persons to determine the sensitivities of currently available serologic techniques. Serial serum samples were obtained from 51 newly infected persons in a cohort of 1,153 homosexual or bisexual men participating in the Baltimore Center of the Multi-Center AIDS Cohort Study during the first 2.5 years of follow-up. Of 51 participants, 45 seroconverted between any two seminannual visits and 6 were found to have been infected just prior to study entry. Five enzyme-linked immunosorbent assays (ELISAs), two immunoblots, and an HIV-1 P24 antigen capture assay were performed on a panel of all serial serum samples from these individuals. The sensitivity of ELISAs varied between 50 and 84% in seroconverters with less-developed antibody response. In this group of seroconverters, the most sensitive antibody assay was an immunoblot from Biotech (95%) and HIV-1 P24 was found infrequently (9.5%). The sensitivities of ELISAs and immunoblot were 100% in individuals with more-developed antibody patterns, and no HIV-1 P24 was detected among them.

Ocular manifestations of acquired immune deficiency syndrome.

The ocular complications of acquired immune deficiency syndrome (AIDS) include: (1) a noninfectious microangiopathy, most often seen in the retina, consisting of cotton-wool spots with or without intraretinal hemorrhages and other microvascular abnormalities; (2) opportunistic ocular infections, primarily cytomegalovirus (CMV) retinitis; (3) conjunctival, eyelid, or orbital involvement by those neoplasms seen in patients with AIDS (i.e., Kaposi's sarcoma and lymphoma); and (4) neuro-ophthalmic lesions. In a series of 200 AIDS patients evaluated clinically, AIDS retinopathy was present in 66.5%. Sixty-four percent had cotton-wool spots, and 12% had intraretinal hemorrhages. Cytomegalovirus retinitis was diagnosed in 28% of AIDS patients. Neuro-ophthalmic lesions were found in 8% of all AIDS patients and were present in 33% of those patients with cryptococcal meningitis. Acquired immune deficiency syndrome retinopathy was present in 40% of 35 patients with the AIDS-related complex (ARC) and in 1.3% of 232 patients with asymptomatic human immunodeficiency virus (HIV) infection, evaluated photographically. These results suggest that the prevalence of AIDS retinopathy increases with increasing severity of HIV infection, and that CMV retinitis presents a significant vision-threatening problem in AIDS patients.