Robert S. Klein

A Prospective Study of the Risk of Tuberculosis among Intravenous Drug Users with Human Immunodeficiency Virus Infection

To determine the risk of active tuberculosis associated with human immunodeficiency virus (HIV) infection, we prospectively studied 520 intravenous drug users enrolled in a methadone-maintenance program. Tuberculin skin testing and testing for HIV antibody were performed in all subjects. Forty-nine of 217 HIV-seropositive subjects (23 percent) and 62 of 303 HIV-seronegative subjects (20 percent) had a positive response to skin testing with purified protein derivative (PPD) tuberculin before entry into the study. The rates of conversion from a negative to a positive PPD test were similar for seropositive subjects (15 of 131; 11 percent) and seronegative subjects (26 of 202; 13 percent) who were retested during the follow-up period (mean, 22 months). Active tuberculosis developed in eight of the HIV-seropositive subjects (4 percent) and none of the seronegative subjects during the study period (P less than 0.002). Seven of the eight cases of tuberculosis occurred in HIV-seropositive subjects with a prior positive PPD test (7.9 cases per 100 person-years, as compared with 0.3 case per 100 person-years among seropositive subjects without a prior positive PPD test; rate ratio, 24.0; P less than 0.0001). We conclude that, although the prevalence and incidence of tuberculous infection were similar for both HIV-seropositive and HIV-seronegative intravenous drug users, the risk of active tuberculosis was elevated only for seropositive subjects. These data also suggest that in HIV-infected persons tuberculosis most often results from the reactivation of latent tuberculous infection; our results lend support to recommendations for the aggressive use of chemoprophylaxis against tuberculosis in patients with HIV infection and a positive PPD test.

Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome.

We studied the frequency with which unexplained oral candidiasis led to unequivocal acquired immunodeficiency syndrome (AIDS) in patients at risk. Twenty-two previously healthy adults with unexplained oral candidiasis, of whom the 19 tested had a reversed T4/T8 ratio and 20 had generalized lymphadenopathy, were compared with 20 similar patients with a reversed T4/T8 ratio and generalized lymphadenopathy who did not have oral candidiasis. All were intravenous-drug abusers, homosexual or bisexual men, or both. Thirteen of the 22 patients with oral candidiasis (59 per cent) acquired a major opportunistic infection or Kaposis sarcoma at a median of three months (range, 1 to 23) as compared with none of 20 patients with generalized lymphadenopathy and immunodeficiency but without candidiasis who were followed for a median of 12 months (range, 5 to 21) (P less than 0.001). AIDS developed in 12 of 15 patients with candidiasis and T4/T8 ratios less than or equal to 0.51, as compared with none of four with ratios equal to or greater than 0.60 (P less than 0.01). We conclude that in patients at high risk for AIDS, the presence of unexplained oral candidiasis predicts the development of serious opportunistic infections more than 50 per cent of the time. Whether the remainder will have AIDS is not yet known.

Association of Streptococcus bovis with carcinoma of the colon.

Two patients with colonic adenocarcinoma and Streptococcus bovis endocarditis suggested a possible association between the two. Non-enterococcal Group D streptococci were isolated from fecal cultures of 11 of 105 controls, 35 of 63 patients with carcinoma of the colon, seven of 25 with inflammatory bowel disease, four of 21 with non-colonic neoplasms and five of 37 with other gastrointestinal disorders. All such streptococci examined for lactose fermentation were S. bovis. The prevalence of S. bovis in fecal cultures from patients with carcinoma of the colon was significantly increased (P less than 0.001) as compared to that in controls, and also to all other groups (P less than 0.001). No other group had results significantly different from those of controls (P less than 0.05) although patients with inflammatory bowel disease were more frequently carriers. The carrier state was unrelated to age, hospitalization status, colonic stasis, gastrointestinal bleeding or recent barium-enema examination. The implications of this association are unknown.

Clinical Manifestations and Predictors of Disease Progression in Drug Users with Human Immunodeficiency Virus Infection

BACKGROUND AND METHODS To examine the clinical course of human immunodeficiency virus (HIV) infection in injection-drug users, we conducted a prospective study of a cohort of patients in a methadone-treatment program in New York City from July 1985 through December 1990. The patients underwent standardized evaluations at base line and semiannually thereafter and received on-site primary medical care. Rates of progression to the acquired immunodeficiency syndrome (AIDS) and major outcomes before the development of AIDS were examined by univariate analyses; the risk of AIDS was also assessed by product-limit survival analysis and proportional-hazards regression. RESULTS Of 318 HIV-seropositive patients who did not yet have AIDS (171 men and 147 women), 90 were black, 179 were Hispanic, and 49 were white; the median age was 33 years. Over a median of 3.0 years of follow-up, 55 (17 percent) received a diagnosis of AIDS (incidence per 100 person-years, 5.8). Major outcomes before the development of AIDS included oral candidiasis (incidence per 100 person-years, 11.2), pyogenic bacterial infections including pneumonia and sepsis (8.0), pulmonary tuberculosis (1.2), multiple constitutional symptoms (13.6), and herpes zoster (1.3). There were 41 deaths from AIDS, and 13 seropositive patients without AIDS (4.1 percent) died of bacterial infections, as compared with only 1 of 411 seronegative patients studied (P < 0.001). The incidence of AIDS was 62 percent lower among those who took zidovudine than among those who did not (P = 0.02). In the multivariate analysis, progression to AIDS was best predicted by low numbers and percentages of CD4+ lymphocytes, nonuse of zidovudine, and the presence of oral candidiasis, bacterial infections, or tuberculosis. There was no consistent relation between progression to disease and the continued use of injection drugs. CONCLUSIONS HIV-infected injection-drug users have progression to AIDS at rates comparable to those of other HIV-infected groups, but they have substantial pre-AIDS morbidity and mortality, particularly from bacterial infections, which also appear to predict disease progression.

Prevalence, Incidence, and Type-Specific Persistence of Human Papillomavirus in Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Women

Human immunodeficiency virus (HIV) infection and related immunosuppression are associated with excess risk for cervical neoplasia and human papillomavirus (HPV) persistence. Type-specific HPV infection was assessed at 6-month intervals for HIV-positive and HIV-negative women (median follow-up, 2.5 and 2.9 years, respectively). The type-specific incidence of HPV infection was determined, and risk factors for HPV persistence were investigated by statistical methods that accounted for repeated measurements. HIV-positive women were 1.8, 2.1, and 2.7 times more likely to have high-, intermediate-, and low-risk HPV infections, respectively, compared with HIV-negative women. In multivariate analysis, high viral signal, but not viral risk category, was independently associated with persistence among HIV-positive subjects (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-2.9). Furthermore, persistence was 1.9 (95% CI, 1.5-2.3) times greater if the subject had a CD4 cell count <200 cells/microL (vs. >500 cells/microL). Thus, HIV infection and immunosuppression play an important role in modulating the natural history of HPV infection.

Immunodeficiency in Female Sexual Partners of Men with the Acquired Immunodeficiency Syndrome

Because the current outbreak of acquired immunodeficiency syndrome (AIDS) among previously healthy adults may be caused by a transmissible biologic agent, and because it may be preceded by immunologic abnormalities with or without a prodromal illness, we studied seven female sexual partners of male patients with the syndrome. The male patients were all drug abusers. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS (generalized lymphadenopathy, lymphopenia, and a decreased ratio of helper to suppressor T cells), and four others had generalized lymphadenopathy or lymphopenia, with or without a decreased ratio of helper to suppressor T cells. Only one woman had no abnormalities. These findings suggest that AIDS may be transmitted between heterosexual men and women.

High risk of human papillomavirus infection and cervical squamous intraepithelial lesions among women with symptomatic human immunodeficiency virus infection

We investigated the relationship of human papillomavirus (by cervicovaginal lavage and Southern blot), human immunodeficiency virus, and squamous intraepithelial lesions in 96 high-risk women in the Bronx, New York. Antibodies for human immunodeficiency virus were detected in 51 (53%) women. Of the 33 women with symptomatic human immunodeficiency virus infection, 23 (70%) had human papillomavirus infection compared with 4 of 18 (22%) asymptomatic women who were human immunodeficiency virus seropositive and 10 of 45 (22%) uninfected women (p less than 0.0001). The rate of squamous intraepithelial lesions was 52% (14 of 27) for women with both viruses detected, 18% (6 of 34) for women with either virus detected, and 9% (3 of 35) for uninfected women. Among symptomatic human immunodeficiency virus-infected women, a strong association between human papillomavirus infection and squamous intraepithelial lesions was demonstrated (odds ratio, 12; 95% confidence interval, 1.3 to 108). Risk was highest for younger women from ethnic or racial minority groups. Advanced human immunodeficiency virus-related disease, with its associated immunosuppression, seems to exacerbate human papillomavirus-mediated cervical cytologic abnormalities. Public health measures are needed to provide Papanicolaou smear screening and appropriate clinical follow-up and treatment for women at high risk for human immunodeficiency virus infection.

Lack of transmission of HTLV-III/LAV infection to household contacts of patients with AIDS or AIDS-related complex with oral candidiasis.

To determine the risk of transmission of human T-cell lymphotropic virus Type III/lymphadenopathy-associated virus (HTLV-III/LAV) to close but nonsexual contacts of patients with the acquired immunodeficiency syndrome (AIDS), we studied the nonsexual household contacts of patients with AIDS or the AIDS-related complex with oral candidiasis. Detailed interviews, physical examinations, and tests for serum antibody to HTLV-III/LAV were performed on 101 household contacts of 39 AIDS patients (68 children and 33 adults), all of whom had lived in the same household with an index patient for at least three months. These contacts had shared household items and facilities and had close personal interaction with the patient for a median of 22 months (range, 3 to 48) during the period of presumed infectivity. Only 1 of 101 household contacts--a five-year-old child--had evidence of infection with the virus, which had probably been acquired perinatally rather than through horizontal transmission. This study indicates that household contacts who are not sexual partners of, or born to, patients with AIDS are at minimal or no risk of infection with HTLV-III/LAV.

Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection.

Background:Osteopenia has been described in HIV-infected persons, but most studies have not focused on aging men, have not included an HIV-negative comparison group with similar risks to those of the HIV-infected men, or lacked data on fracture rates. Methods:We analyzed bone mineral density (BMD) and incident fractures in 559 men who were ≥ 49 years old with or at-risk for HIV, including 328 with and 231 without HIV infection. Results:Median age was 55 years, 56% were black and 89% had used illicit drugs. In unadjusted analysis, BMD was lower in HIV-infected compared with HIV-uninfected men at the femoral neck (0.97 ± 0.14 versus 1.00 ± 0.15 g/cm2; P < 0.05) and lumbar spine (1.17 ± 0.20 versus 1.20 ± 0.21 g/cm2; P = 0.06); both differences were significant (P < 0.05) after adjusting for age, weight, race, testosterone level, and prednisone and illicit drug use. Non-black race and body weight were independently associated with BMD at both measurement sites and methadone therapy was independently associated with spine BMD. Among HIV-infected men, 87% had taken antiretrovirals and 74% had taken protease inhibitors, but their use was not associated with BMD. Among men who had at least one subsequent study visit (94%), incident fracture rates per 100 person-years differed among men with normal BMD, osteopenia and osteoporosis (1.4 versus 3.6 versus 6.5; P < 0.01). A 38% increase in fracture rate among HIV-infected men was not statistically significant. Conclusions:HIV infection is independently associated with modestly reduced BMD in aging men, and decreased BMD is associated with increased fracture risk.

Increased risk of bacterial pneumonia in HIV-infected intravenous drug users without AIDS.

Although patients with AIDS have been noted to be at risk for bacterial pneumonia as well as opportunistic infections, little is known about the risk of bacterial pneumonia in HIV-infected populations without AIDS. To determine the incidence of bacterial pneumonia in a well defined population of intravenous drug users (IVDUs), and to examine any association with HIV infection, we prospectively studied 433 IVDUs without AIDS, enrolled in a longitudinal study of HIV infection in an out-patient methadone maintenance program. At enrollment, 144 (33.3%) subjects were HIV-seropositive, 289 (66.7%) were seronegative. Over a 12-month period, 14 out of 144 (9.7%) seropositive subjects were hospitalized for community-acquired bacterial pneumonia, compared with six out of 289 (2.1%) seronegative subjects. The cumulative yearly incidence of bacterial pneumonia was 97 out of 1000 for seropositives and 21 out of 1000 for seronegatives (risk ratio = 4.7, P less than 0.001). Eleven out of 14 (78.6%) cases among the seropositive patients were due to either Streptococcus pneumoniae [5] or Hemophilus influenzae [6]. Two out of 14 (14.3%) cases among the seropositives were fatal. Stratifying by level of intravenous drug use indicated that even among subjects not reporting active intravenous drug use at study entry, eight out of 82 (9.8%) seropositives compared with three out of 211 (1.4%) seronegatives were hospitalized for bacterial pneumonia over the study period (risk ratio = 6.9, P less than 0.01). This study shows a markedly increased incidence of bacterial pneumonia associated with HIV infection in IVDUs without AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)