Increased all-cause and cancer mortality in HTLV-II infection.

BACKGROUND: Human T-lymphotropic virus (HTLV)-I and HTLV-II cause chronic human retroviral infections, but few studies have examined the impact of either virus on survival among otherwise healthy individuals. The authors analyzed all-cause and cancer mortality in a prospective cohort of 155 HTLV-I, 387 HTLV-II, and 799 seronegative subjects. METHODS: Vital status was ascertained using death certificates, the US Social Security Death Index or family report, and causes of death were grouped into 9 categories. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: After a median follow-up of 15.9 years, there were 105 deaths: 22 HTLV-I, 41 HTLV-II, and 42 HTLV-seronegative. Cancer was the predominant cause of death, resulting in 8 HTLV-I, 17 HTLV-II, and 15 HTLV-seronegative deaths. After adjustment for confounding, HTLV-I status was not significantly associated with increased all-cause mortality, though there was a positive trend (HR: 1.6, 95% CI: 0.8 to 3.1). HTLV-II status was strongly associated with increased all-cause (HR: 2.4, 95% CI: 1.4 to 4.4) and cancer mortality (HR: 3.8, 95% CI: 1.6 to 9.2). CONCLUSIONS: The observed associations of HTLV-II with all-cause and cancer mortality could reflect biological effects of HTLV-II infection, residual confounding by socioeconomic status or other factors, or differential access to health care and cancer screening.

Clinical outcomes and disease progression among patients coinfected with HIV and human T lymphotropic virus types 1 and 2.

The goal of this study was to investigate clinical outcomes and survival probabilities among persons coinfected with human immunodeficiency virus (HIV) and human T lymphotropic viruses types 1 and 2 (HTLV-I/II). A nonconcurrent cohort study of 1033 HIV-infected individuals was also conducted. Sixty-two patients were coinfected with HTLV-I, and 141 patients were coinfected with HTLV-II. HTLV-I/II coinfection was highly associated with African-American race/ethnicity, age of >36 years, higher CD4(+) T cell count at baseline and over time, and history of injection drug use. Coinfected patients were more likely to have neurologic complications, thrombocytopenia, respiratory and urinary tract infections, and hepatitis C. Despite having higher CD4(+) T cell counts over time, there was no difference in the incidence of opportunistic infections. Progression to both acquired immunodeficiency syndrome (AIDS; adjusted hazard ratio [aHR], 0.50; 95% confidence interval [CI], 0.25-0.98) and death (aHR, 0.57, 95% CI, 0.37-0.89) were slower among HTLV-II-coinfected patients, compared with time-entry- and CD4(+) T cell count-matched control subjects. In conclusion, HIV-HTLV-I/II coinfection may result in improved survival and delayed progression to AIDS, but this happens at the expense of an increased frequency of other of clinical complications.

Increased mortality associated with HTLV-II infection in blood donors: a prospective cohort study.

BACKGROUND: HTLV-I is associated with adult T-cell leukemia, and both HTLV-I and -II are associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Several published reports suggest that HTLV-I may lead to decreased survival, but HTLV-II has not previously been associated with mortality. RESULTS: We examined deaths among 138 HTLV-I, 358 HTLV-II, and 759 uninfected controls enrolled in a prospective cohort study of U.S. blood donors followed biannually since 1992. Proportional hazards models yielded hazard ratios (HRs) for the association between mortality and HTLV infection, controlling for sex, race/ethnicity, age, income, educational level, blood center, smoking, injection drug use history, alcohol intake, hepatitis C status and autologous donation. After a median follow-up of 8.6 years, there were 45 confirmed subject deaths. HTLV-I infection did not convey a statistically significant excess risk of mortality (unadjusted HR 1.9, 95%CI 0.8-4.4; adjusted HR 1.9, 95%CI 0.8-4.6). HTLV-II was associated with death in both the unadjusted model (HR 2.8, 95%CI 1.5-5.5) and in the adjusted model (HR 2.3, 95%CI 1.1-4.9). No single cause of death appeared responsible for the HTLV-II effect. CONCLUSIONS: After adjusting for known and potential confounders, HTLV-II infection is associated with increased mortality among healthy blood donors. If replicated in other cohorts, this finding has implications for both HTLV pathogenesis and counseling of infected persons.

Respiratory and urinary tract infections, arthritis, and asthma associated with HTLV-I and HTLV-II infection.

Human T-lymphotropic virus types I and II (HTLV-I and -II) cause myelopathy; HTLV-I, but not HTLV-II, causes adult T-cell leukemia. Whether HTLV-II is associated with other diseases is unknown. Using survival analysis, we studied medical history data from a prospective cohort of HTLV-I- and HTLV-II-infected and -uninfected blood donors, all HIV seronegative. A total of 152 HTLV-I, 387 HTLV-II, and 799 uninfected donors were enrolled and followed for a median of 4.4, 4.3, and 4.4 years, respectively. HTLV-II participants had significantly increased incidences of acute bronchitis (incidence ratio [IR] = 1.68), bladder or kidney infection (IR = 1.55), arthritis (IR = 2.66), and asthma (IR = 3.28), and a borderline increase in pneumonia (IR = 1.82, 95% confidence interval [CI] 0.98 to 3.38). HTLV-I participants had significantly increased incidences of bladder or kidney infection (IR = 1.82), and arthritis (IR = 2.84). We conclude that HTLV-II infection may inhibit immunologic responses to respiratory infections and that both HTLV-I and -II may induce inflammatory or autoimmune reactions.

Cause-specific mortality associated with HIV and HTLV-II infections among injecting drug users in the USA.

BACKGROUND: Human T-lymphotropic virus type II (HTLV-II) is widespread among injecting drug users (IDU) and may contribute to the risk of leukemia/lymphoma, neurodegenerative disease, and perhaps pneumonia, especially with HIV co-infection. METHODS: In 1987--1991, 6570 IDU were tested for HIV and HTLV-II antibodies. In 1998, they were matched to the National Death Index. Numbers of observed deaths of each cause were compared by standardized mortality ratios with the numbers expected, using sex-, race-, age-, and year-specific rates in the general population. Relative risk (RR) associated with each virus, compared to uninfected drug users, was estimated by Poisson modeling. RESULTS: There were 1351 deaths, including 683 (15%) of 4604 participants who enrolled seronegative for both viruses; 328 (47%) of 701 who had HIV but not HTLV-II infection; 220 (21%) of 1033 who had HTLV-II but not HIV infection; and 120 (52%) of 232 who were infected by both viruses. Compared to the general population, mortality for participants with neither virus was increased 4.3-fold [95% confidence interval (CI), 4.0--4.7] and was significantly elevated for virtually every cause of death. With HIV, mortality from medical causes, but not external causes, was increased 3.7-fold (95% CI, 3.3--4.2), particularly with AIDS and related conditions. With HTLV-II, all-cause mortality was reduced (RR, 0.8; 95% CI, 0.7--0.9), with no statistically significant reduction or elevation for any specific cause. A non-significant excess of tuberculosis deaths (RR, 4.6; 95% CI, 0.8--25.2) was noted with HTLV-II, but there was no excess mortality from leukemia/lymphoma, other malignancies, or neurodegenerative disease. CONCLUSIONS: Without HIV or HTLV-II, IDU had profoundly increased mortality from medical and external causes. HIV was specifically associated with death due to AIDS and related conditions. HTLV-II infection was not significantly associated with mortality from any cause, suggesting that it is not a significant human pathogen, even when present with HIV infection.

Co-infection with HIV-1/HTLV-II and the risk of progression to AIDS and death. The Oslo HIV Cohort Study Group.

Human T-cell lymphotropic virus (HTLV) types I and II were the first discovered human retroviruses. While HTLV-I has been clearly associated with disease, the health implications of HTLV-II infection are still unsettled. A prospective epidemiological study of 409 HIV-infected subjects of different transmission categories was performed to study the presence of HTLV-II antibodies, and whether HTLV-II antibodies are associated with the progression to AIDS and to death of any cause. Of 409 subjects, 30 (7.3%) were HTLV-II positive at study entry; 2 subjects seroconverted during follow-up. In the HTLV-II-positive group 2 were heterosexually HIV infected, 28 (of whom 2 were seroconverters) were IDUs and 2 were homosexual men. When controlling for transmission category, gender, age and CD4+ lymphocyte count at study entry, the relative risk of AIDS progression for the HTLV-II-positive group was 2.1 (0.8-5.1, 95% confidence interval (CI)) as compared to the HTLV-II-negative group. The adjusted relative risk of dying was 2.1 (1.0-4.3, 95% CI). When studying IDUs separately, the adjusted relative risk of AIDS progression was 2.3 (0.8-6.9, 95% CI) and the relative risk of dying was 2.0 (0.9-4.6, 95% CI). The results of this study suggest that HTLV-II is a cofactor in HIV disease progression. The number of HTLV-II-infected subjects, was, however, small, and insufficient control of confounding factors must be taken into consideration.