Myelopathy among Brazilians coinfected with human T-cell lymphotropic virus type I and HIV.

OBJECTIVE: To determine whether subjects coinfected with HTLV-I and HIV have a higher frequency of myelopathy than subjects singly infected with HIV. DESIGN: A prospective, nested case-control study of HTLV-I and HIV coinfected (cases) and HIV singly infected adults (controls) participating in a prospective HIV cohort study at a university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. MEASUREMENTS: Subjects were evaluated for evidence of myelopathy by a neurologist unaware of their HTLV serologic status. Patients with at least two pyramidal signs, such as paresis, hypertonicity or spasticity, hyperreflexia, clonus, diminished or absent superficial reflexes, or the presence of pathologic reflexes (e.g., Babinski or Hoffmann), were defined as having myelopathy. Myelopathy severity was quantified using the Kurtzke Functional Disability Scale (FDS); patients with FDS scores > or = 4 were considered to have significant myelopathy. Selected patients with myelopathy underwent lumbar puncture for the evaluation of intrathecal synthesis of HTLV-I antibodies. RESULTS: Of 15 coinfected subjects, 11 (73%) had evidence of myelopathy versus 10 of 62 subjects (16%) with HIV single infection (adjusted odds ratio [OR] = 13.0, p = 0.00002). When only myelopathy patients with FDS scores of > or = 2 or > or = 4 were included, the association between coinfection and the presence of myelopathy remained (OR = 7.3, p = 0.0003 for scores > or = 2; and OR = 8.9 for scores > or = 4, p = 0.04). In addition, a higher proportion of coinfected subjects had peripheral neuropathy (40%) than controls (16%) (OR = 3.5, p = 0.07). CONCLUSION: Coinfection with HTLV-I was strongly associated with myelopathy among subjects infected with HIV. The relative contribution of HTLV-I versus HIV in the pathogenesis of coinfection-associated myelopathy is not known. Coinfection may also be associated with peripheral neuropathy. Further studies are needed to elucidate the mechanisms of coinfection-associated neurologic conditions.

Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection.

We enrolled 427 consecutive patients with tuberculosis diagnosed in Cité Soleil, Haiti in a trial of short-course intermittent therapy. All patients received supervised therapy with isoniazid, rifampin, pyrazinamide, and ethambutol thrice weekly for 8 wk, followed by isoniazid and rifampin thrice weekly for 18 wk. At entry, the 177 human immunodeficiency virus (HIV)-infected patients (42%) were found significantly more likely to have extrapulmonary tuberculosis and negative tuberculin skin tests (p < 0.05). Treatment was well tolerated by both groups of patients, and adherence to the treatment regimen was over 90%. Among patients with pulmonary or intrathoracic tuberculosis, 9% of HIV-seropositive and 1% of HIV-seronegative patients died during therapy (p < 0.001), whereas 81% and 87%, respectively, of those in the two groups were cured. Relapses occurred in 5.4% of HIV-seropositive and 2.8% of HIV-seronegative patients who completed treatment (p = 0.36). Survival after tuberculosis was poorer in HIV-seropositive patients, whose probability of dying was 33% at 18 mo after diagnosis as compared with 3% for HIV-seronegative patients (p < 0.001). HIV-seropositive patients who died had significantly lower median CD4 lymphocyte counts than did HIV-seropositive patients who survived (p < 0.001). Treatment of tuberculosis with short-course, thrice-weekly, supervised therapy in the setting of a developing country is highly efficacious in both HIV-seropositive and -seronegative patients.

Coinfection with human T-cell lymphotropic virus type I and HIV in Brazil. Impact on markers of HIV disease progression.

OBJECTIVES: To study the effect of human T-cell lymph-tropic virus type I (HTLV-I) on markers of human immunodeficiency virus (HIV) disease progression. DESIGN: A retrospective, nested case-control study. SETTING: A university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. PARTICIPANTS: Human immunodeficiency virus-seropositive adults participating in a prospective HIV cohort study. MAIN OUTCOME MEASURES: The HIV clinical stage, CD4+ lymphocyte counts, and other laboratory parameters in 27 individuals infected with HIV and HTLV-I (coinfection) and 99 age-matched, HIV-seropositive, HTLV-seronegative controls (single infection). RESULTS: Variables independently associated with coinfection included higher CD4+ lymphocyte count (odds ratio [OR], 2.3; 95% confidence limits [CL], 1.3, 4.1), higher CD4+ percentage (OR, 2.0; 95% CL, 1.3, 3.2), beta 2-microglobulin level of 254 nmol/L or more (OR, 6.8; 95% CL, 1.3, 35.4), World Health Organization stages 3 and 4 (OR, 4.4; 95% CL, 1.1, 18.0), and reporting a parenteral risk factor (OR, 7.4; 95% CL, 1.4, 38.9). When stratified by p24 antigenemia, coinfection was associated with an estimated 82% higher CD4+ lymphocyte count (P < .05). CONCLUSION: Coinfection was associated with higher CD4+ lymphocyte counts, more advanced clinical disease, and higher beta 2-microglobulin levels than HIV infection alone. The higher mean CD4+ lymphocyte count does not appear to offer immunologic benefit. Caution should be exercised when using CD4+ lymphocytes as a surrogate marker in studies of HIV infection in populations where HTLV-I is prevalent. Further studies are needed to address whether current CD4+ lymphocyte values for the initiation of antiretroviral therapy and chemoprophylaxis against opportunistic infections in HIV infection are appropriate in coinfection.

HIV-1 and HTLV-I in sexually transmitted disease clinics in the Dominican Republic.

A cross-sectional seroprevalence study of human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I) was undertaken among 494 attendees in two Santo Domingo sexually transmitted disease clinics in 1989. All participants were evaluated for Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and genital ulcers. Of the 494 participants, 15 (3.0%) were positive for HIV-1 and 14 (2.8%) were positive for HTLV-I. Twelve of 371 (3.2%) men were HIV-1 seropositive: 0 of 68 homosexual/bisexual and 12 (4.0%) of 302 heterosexual men (one seronegative male could not be classified). Three (2.4%) of 123 women were HIV-1 seropositive. One (1.5%) homosexual/bisexual man, five (1.7%) heterosexual men, and eight (6.5%) women were HTLV-I seropositive. Among heterosexual men, HIV-1 was associated with multiple lifetime sex partners (O.R. = 5.9; 95% C.I. = 1.4, 23; p = 0.007). HIV-1 was associated with genital ulcer disease among women (p = 0.004). Among women, HTLV-I was associated with professional sex work (O.R. = 18; 95% C.I. = 2.1, > 100; p = 0.001). These findings suggest the need for control of sexually transmitted diseases and targeted educational programs for prevention of HIV-1 and HTLV-I among individuals with high-risk behaviors in the Dominican Republic.

Herpes simplex virus type 2 infection, syphilis, and hepatitis B virus infection in Haitian women with human immunodeficiency virus type 1 and human T lymphotropic virus type I infections. The Johns Hopkins University (JHU)/Centre pour le Developpement et la Santé (CDS) HIV Study Group.

Antibodies to herpes simplex virus type 2 (HSV-2), antibodies to hepatitis B virus (HBV) core antigen (anti-HBc), and VDRL antibodies (serologic evidence of syphilis) were evaluated in women known to be infected with human immunodeficiency virus type 1 (HIV-1) (n = 95) or human T lymphotropic virus type I (HTLV-I) (n = 45) and controls (n = 89). HIV-1-seropositive women were more likely than controls to have antibodies to HSV-2 (88% vs. 54%; P less than .001), anti-HBc (67% vs. 43%; P = .008), and VDRL antibodies (21% vs. 8%; P = .02). Similarly, HTLV-I-seropositive women were more likely than controls to have antibodies to HSV-2 (82% vs. 54%; P = .003) and anti-HBc (67% vs. 43%; P = .008). There was no evidence that HIV-1 or HTLV-I predisposed to chronic hepatitis B virus infection. The stronger associations between HIV-1 and HTLV-I with HSV-2 than the associations with syphilis or HBV are consistent with the hypothesis that recurrent disruptions of mucous membranes caused by HSV-2 infections predispose to sexual transmission of HIV-1 and HTLV-I.

Diagnostic accuracy of three clinical case definitions for advanced HIV disease.

OBJECTIVE: To assess the accuracy of three clinical case definitions for advanced HIV disease: the World Health Organization (WHO) case definition, and the original and revised Caracas case definitions. DESIGN: Retrospective chart review. SETTING: A clinic for patients with all stages of HIV infection at the Johns Hopkins Hospital, Baltimore, [correction of Bethesda] Maryland, USA, a tertiary care university hospital. PATIENTS, PARTICIPANTS: Two hundred and twenty-four HIV-positive adults who underwent initial evaluation between 1 January 1990 and 31 December 1990. MAIN OUTCOME MEASURES: A score for each definition was assigned based on initial evaluation. The sensitivity, specificity, and predictive values were calculated using the Centers for Disease Control (CDC) staging criteria, and results were correlated with total CD4 cell counts. RESULTS: The sensitivities of the WHO, and the original and revised Caracas definitions were 40, 67, and 60%, respectively, using CDC disease stage IV as a positive standard. Specificities were between 99 and 100%, using CDC stage II-III disease as a negative standard. Mean CD4 cell counts for patients with positive scores were 184, 160, and 158 x 10(6)/l, respectively, compared to 191 x 10(6)/l for CDC stage IV patients. Sensitivity was lower when the positive standard was expanded to include all patients with CD4 cell counts less than 200 x 10(6)/l. CONCLUSIONS: In our study population, case definitions were specific, but only moderately sensitive for advanced HIV disease. Prospective studies should be conducted in diverse geographic regions, using lymphocyte or CD4 cell counts when possible.

PIP: The 1st case definition for AIDS was developed by the Centers for Disease Control (CDC) in 1982. WHO adopted CDC definitions for use in some countries and also developed a clinical case definition where HIV serology tests were not feasible. A multivariate analysis of data of Brazilian AIDS patients with positive HIV serology provided the basis for the Caracas definition in 1989 and it subsequent revision. The accuracy of these 3 clinical definitions was evaluated to see their predictive value in an advanced stage of AIDS. The records of 224 HIV-positive adults were reviewed in 1990. Scores were assigned to various symptoms. 80% of men and 20% of women with a median age of 33 years; 1/4 were white and 2/3 were black. 1/3 were homosexuals and 1.2 were iv drug users. 139 were asymptomatic (CDC stage I-II) and 85 were symptomatic (CDC stage IV). 58 patients had total CD4 cell counts of over 500 x 1 million/1; 91 had 200-500 x 1 million/l; and 70 had 200 x 1 million/1. 48 were taking zidovudine and Pneumocytis carinii drugs. The sensitivities of the WHO, original Caracas definition, and revised Caracas definition were 40%, 67%. and 60%, respectively, with 99-100% specificities and positive predictive values of 97-100%. The mean CD4 cell counts for the WHO, original and revised Caracas definitions were 184, 160, and 158 x 1 million/1, respectively, compared with 199 x 1 million/1 of patients with CDC stage IV disease. The predictive values of the 3 definitions for CD4 cell counts 200 x 1 million/1 reached 62%, 73%, and 71% vs. only 59% for CDC stage IV patients. The combination of stage IV symptoms or a CD4 cell count 200 x 1 million/1 produced sensitivities of 31%, 53%, and 47%, respectively, with 100% specificity and positive predictive values. The definitions were highly specific, but only moderately sensitive for advanced AIDS; the Caracas definitions were more sensitive than the WHO definition.

Transmission of HIV-1 infections from mothers to infants in Haiti. Impact on childhood mortality and malnutrition. The CDS/JHU AIDS Project Team.

Of 4588 pregnant women in a high-risk Haitian population, 443 (9.7%) were serologically positive for the human immunodeficiency virus type 1 (HIV-1). Infants born to women who were HIV-1 seropositive were more likely to be premature, of low birth weight, and malnourished at 3 and 6 months of age than were infants born to women who were HIV-1 seronegative. Increased mortality was observed in infants born to women who were HIV-1 seropositive by 3 months of age. At 12 months of age, 23.4% of the infants born to women who were HIV-1 seropositive had died compared with 10.8% of the infants born to women who were HIV-1 seronegative; at 24 months of age, the mortality rates were 31.3% and 14.2%, respectively. Maternal HIV-1 infections resulted in an 11.7% increase in the overall infant mortality rate in this population. The estimated mother-to-infant HIV-1 transmission rate in these breast-fed infants was 25%, similar to the rates reported for non-breast-fed populations in the United States and Europe.

Human immunodeficiency virus neutralizing antibodies in sera from North Americans and Africans.

Neutralizing antibodies (NAs) against four isolates of human immunodeficiency virus type 1 (HIV-1) were assayed in HIV-1 antibody positive sera from the United States, Haiti, Zimbabwe, and Zaire. Overall, there were NAs detected in 95, 81, 60, and 73% of sera with reciprocal geometric mean titers (GMTs) of 626, 23, 10, and 20, respectively, against HIV-1MN, HIV-1IIIB, HIV-1RF, and HIV-1Z3. Sera from North America had significantly higher NA titers against HIV-1MN. In each country, the highest antibody titers observed were against the MN strain. Otherwise, sera from the U.S. neutralized most strongly HIV-1IIIB, sera from Zaire neutralized most strongly HIV-1Z3, and sera from Zimbabwe had equal titers against all three viruses. The differences between countries were reflected in analyses of NA titers of subgroups classified on the basis of clinical status, indicating that the differences were not likely to be related to differences in clinical status of the patients being tested. Some of this antigenic variation is reflective of known genetic diversity, while some is not. The results suggest that undefined preserved and variable regions containing neutralization epitope(s) exist. These data do not indicate a need to define antigenic subtypes of HIV-1 at present. The existence of conserved neutralization epitope(s) may indicate the potential for broad immunogenicity of appropriately selected vaccine antigens.

HIV-1 in Haitian women 1982-1988. The Cite Soleil/JHU AIDS Project Team.

Pregnant Haitian women (n = 4,474) residing in a periurban slum were interviewed to identify risk factors for sexually transmitted diseases and sera were tested to identify antibodies to HIV-1 and syphilis. The seroprevalence rates for antibodies to HIV-1 increased from 8.9% in 1986 to 9.9% in 1987 and 10.3% in 1988. Sera obtained in 1982 from 533 mothers of young infants in the same community revealed that 7.8% were HIV-1 seropositive. Of women pregnant for the first time in 1986-1988, 6.6% were HIV-1 seropositive and 6.0% had a positive VDRL. The highest seropositivity rates (greater than 15%) were noted in women 20 to 29 years of age with a history of two or more sexual partners in the year prior to pregnancy. Factors independently associated with HIV-1 seropositivity in pregnant women by logistic regression analysis included being unmarried, age 20-29 years, having had more than one sex partner in the year prior to pregnancy, a positive serologic test for syphilis, and smoking. A dose-response effect was noted in the association between HIV-1 seropositivity and smoking. The association between smoking and HIV-1 infections could be confounded by unrecognized behavioral factors or due to a biologic effect of smoking. The continuing high HIV-1 seropositivity rates in pregnant women indicate that current preventive measures are insufficient and increased control efforts are urgently needed.

HIV and HTLV-I infections in the Americas: a regional perspective.

With over 143,000 cases of AIDS reported to the World Health Organization from 145 countries and with an estimated 5 to 10 million people worldwide infected with HIV, AIDS has become firmly established as a global pandemic. In the region of the Americas over 100,862 cases of AIDS have been reported with indigenous transmission documented in 45 to 46 countries. While North America has the highest annual number of AIDS cases per population, with 72 cases/million, the Caribbean subregion has a disproportionately high number of cases, with annual rates as high as 200 to 300 cases/million population for some countries. Despite differences in absolute number of cases, there has been a remarkable similarity in the temporal rate of increase of AIDS in the countries of the Americas, reflecting delayed introduction of the virus to some areas with an early exponential increase similar to that observed initially in the United States. Although the modes of transmission of HIV are the same throughout the region, evidence of increasing bisexual and heterosexual transmission, particularly in the Caribbean subregion, has resulted in a lower male-to-female ratio of AIDS cases and increased perinatal transmission. Clinically, a resurgence of diarrheal diseases, respiratory infections, and tuberculosis has been documented in association with HIV infection in many tropical countries of the Americas. With relatively high rates of HTLV-I infection already established in the Caribbean subregion, the overall public health problems of the Americas will be markedly potentiated by further spread of these 2 human retroviruses. If HIV infection continues to penetrate the poor and less advantaged populations in Latin America and the Caribbean, the potential exists for a massive epidemic in the Americas that may rapidly parallel the situation in Africa.

PIP: The article describes in detail the extent and nature of HIV and HTLV-1 infections, and AIDS in the Americas. Surveillance statistics are provided for general populations, homosexual and bisexual men, IV-drug users, female prostitutes, hemophiliacs, heterosexual partners of HIV-infected persons, blood donors, and pregnant women. As of publication, over 100,862 AIDS cases have been reported in the region, with indigenous transmission documented in 45-46 countries. Clinical manifestations of HIV infection and AIDS are discussed. North America claims the highest annual AIDS cases per population at 72/million, while the Caribbean subregion has a disproportionately high number of cases, with annual rates reaching 200-300/million for some countries. The temporal rate of increase of AIDS cases has, however, been fundamentally comparable for all countries of the Americas. While HIV transmission modes are the same throughout the region, increasingly lower male-female ratios of AIDS cases, and more cases of perinatal transmission especially in Caribbean countries. Diarrheal disease, respiratory infections, and tuberculosis have also been documented as associated with HIV infection in many tropical countries of the Americas. Further, relatively high rates of HTLV-1 infection in the Caribbean will only exacerbate already significant public health problems faced by some countries of the region. Should HIV continue infiltrating poor, disadvantaged populations of Latin America and the Caribbean, HIV infection levels and AIDS could reach epidemic proportions similar to that witnesses in Africa.