In vitro and animal studies suggest that cocaine and heroin increase HIV replication and suppress immune function, whereas epidemiologic studies are inconclusive regarding their effect on HIV infection progression. The authors prospectively examined the association between illicit-drug use and 4 outcome measures (CD4 cell percentage, HIV RNA level, survival to class C diagnosis of HIV infection, and death) in a national cohort of HIV-infected women. Women enrolled between 1989 and 1995 were followed for 5 years and repeatedly interviewed about illicit ("hard")--drug use. Up to 3 periodic urine screens validated self-reported use. Outcomes were compared between hard-drug users (women using cocaine, heroin, methadone, or injecting drugs) and nonusers, adjusting for age, antiretroviral therapy, number of pregnancies, smoking, and baseline CD4 cell percentage. Of 1148 women, 40% reported baseline hard-drug use during pregnancy. In multivariate analyses, hard-drug use was not associated with change in CD4 cell percentage (P = 0.84), HIV RNA level (P = 0.48), or all-cause mortality (relative hazard = 1.10; 95% confidence interval, 0.61-1.98). Hard-drug users did, however, exhibit a higher risk of developing class C diagnoses (relative hazard = 1.65; 95% confidence interval, 1.00-2.72), especially herpes, pulmonary tuberculosis, and recurrent pneumonia. Hard-drug-using women may have a higher risk for nonfatal opportunistic infections.

Human immunodeficiency virus (HIV) type 1 RNA load, CD4 T cell level, and Centers for Disease Control and Prevention (CDC) clinical class history were measured as potential correlates of a CDC class C diagnosis or death in 165 HIV-1-infected children followed from birth. These covariates were assessed at fixed "landmark" ages from 6 to 24 months and were also assessed as time-varying values. Virus load was associated with progression in all analyses, even after adjusting for immunologic and clinical status. This confirms its importance for monitoring pediatric disease progression. CD4 T cell level was associated with disease progression in time-varying but not in adjusted landmark analysis, suggesting that CD4 cells reflects immediate risk more than long-term risk. The distinction between clinical class B and lower classes is prognostic during the first 18 months of life; class C versus classes N/A/B becomes more important as the patient ages. Virologic, immunologic, and clinical status all provide information regarding disease progression risk.

BACKGROUND A growing proportion of AIDS cases in the United States are due to heterosexual transmission of HIV, particularly in women. The risk of heterosexually acquired HIV was prospectively studied in a cohort of inner-city women with no history of parenteral drug use. METHODS Study participants were evaluated at 6-month intervals for the presence of HIV antibody, sexually transmitted diseases, self-reported sexual behavior, and drug use by self-report and urine screening. RESULTS Of 449 initially HIV-negative women who were seen at least once in follow-up, 4 seroconverted to HIV, with a cumulative incidence of 2.4% at 30 months. Risk factors for HIV seroconversion included nonparenteral drug use (p < .02) and anal intercourse (p < .01). Sexually transmitted diseases were not associated with HIV, although the power to detect such an association was limited. In addition, 3 of 4 seroconverters became pregnant, yielding a rate of 55.5 pregnancies/100 person-years of follow-up compared with a rate of 11.1 pregnancies/100 person-years of follow-up in nonseroconverters (p < .03). CONCLUSION The incident rate of heterosexually acquired HIV in this inner-city U.S. cohort of women who were not using parenteral drugs is comparable with that reported in some developing countries where heterosexually acquired HIV is endemic. Most seroconversions appeared related to risk behavior seen in association with nonparenteral drug use. The previously unreported association of incident HIV infection with pregnancy in this cohort may be related to either behavioral or biologic factors.

Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-l-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of <10(5) copies/mL. Women dually infected with HIV-I and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.

Background, A substantial proportion of perinatally acquired infections with the human immunodeficiency virus type 1 (HIV-1) occur at or near delivery, which suggests that obstetrical factors may have an important influence on transmission, We evaluated the relation of such factors and other variables to the perinatal transmission of HIV-1.Methods. The Women and Infants Transmission Study is a prospective, observational study of HIV-1-infected women who were enrolled during pregnancy and followed with their infants for three years after delivery, We studied obstetrical, clinical, immunologic, and virologic data on 525 women who delivered live singleton infants whose HIV-1-infection status was known as of August 31, 1994.Results. Among mothers with membranes that ruptured more than four hours before delivery, the rate of transmission of HIV-1 to the infants was 25 percent, as compared with 14 percent among mothers with membranes that ruptured four hours or less before delivery, In a multivariate analysis, the presence of ruptured membranes for more than four hours nearly doubled the risk of transmission (odds ratio, 1.82; 95 percent confidence interval, 1.10 to 3.00; P = 0.02), regardless of the mode of delivery, The other maternal factors independently associated with transmission were illicit-drug use during pregnancy (odds ratio, 1.90; 95 percent confidence interval, 1.14 to 3.16; P = 0.01), low antenatal CD4+ lymphocyte count (<29 percent of total lymphocytes) (odds ratio, 2.82; 1.67 to 4.76; P<0.001), and birth weight <2500 g (odds ratio, 1.86; 1.03 to 3.34; P = 0.04),Conclusions. The risk of transmission of HIV-1 from mother to infant increases when the fetal membranes rupture more than four hours before delivery.

BACKGROUND AND OBJECTIVES:Human papillomavirus (HPV) infection of the female genital tract is the most common sexually transmitted disease. Although the prevalence of HPV in women without detectable cervical disease has been shown to decline with increasing age, the relationship to sexual behavior has not been investigated.GOAL:To identify risk factors for, and associated with the age-dependent decline in, genital HPV infection in women.STUDY DESIGN:The prevalence of HPV was determined in a cohort of 439 sexually active inner-city women between the ages of 18 and 50 years recruited in Brooklyn, New York. Cervicovaginal cells were collected by lavage, and HPV was detected by low-stringent Southern blot hybridization.RESULTS:The prevalence of HPV infection ranged from 36% in women younger than 25 years of age to 2.8% in women 45 years or older. Logistic regression analysis identified an increased risk for cervical HPV infection to be independently associated with number of sex partners in the past year (odds ratio [OR], 1.04 per yearly increase in age; 95% confidence interval [CI], 1.00 to 1.08), younger age (OR, 0.92 per year increase in age; 95% CI, 0.88 to 0.95), and not living with partner (OR, 2.28; 95% CI, 1.40 to 4.22).CONCLUSIONS:The lower prevalence of HPV infection in older women compared to younger women was found to be independent of sexual behavior. These results suggest that a biologic effect, such as HPV immunity acquired over time and with multiple exposures, may mediate the inverse relationship between age and HPV prevalence.

Cytomegalovirus (CMV) seroprevalence and genital tract shedding in human immunodeficiency virus (HIV)-seronegative and HIV-seropositive women from an urban minority community were investigated. CMV seropositivity was high in both groups: 181 (95.2%) of 190 HIV-negative and 158 (90.3%) of 175 HIV-positive subjects. Cervicovaginal shedding was detected in 8 (4.4%) CMV-positive HIV-negative subjects and 31 (19.6%) HIV-positive subjects (odds ratio [OR], 5.28; P < .001), Multiple logistic regression analysis revealed that CMV shedding was independently associated with younger age (OR = 0.90; P < .001) and concurrent Chlamydia trachomatis or Neisseria gonorrhoeae infection (OR = 3.60; P = .08). However, shedding was observed over a broad age range in HIV-positive subjects, with 54.8% of shedders being greater than or equal to 30 years old. Among HIV-positive subjects, CMV shedding was also associated with decreased CD4 cell counts (P = .04) and, compared with HIV-negative subjects, was significantly higher (P < .001) among subjects with CD4 cell counts <500 X 10(6)/L (26.5% in subjects with counts less than or equal to 200 and 22.1% in subjects with counts of 201-499 X 10(6)/L).

Recent studies on the dynamics of human immunodeficiency virus type 1 (HIV-1) replication have enhanced our understanding of disease pathogenesis. It is now clear that even during the period of clinical latency there is continual highlevel viral replication, CD4+lymphocyte infection, cell death, and new CD4+cell production.1-4The magnitude of the viral and CD4+cell turnover is extraordinary; on average, 108to 109HIV-1 virions and approximately the same number of CD4+cells are produced and destroyed each day.3,4This process takes place primarily in the lymphoid tissue where the virus, though bound to a follicular dendritic cell and coated with neutralizing antibody, remains highly infectious to CD4+T cells.5The discovery of a persistently high level of viral turnover suggests that sensitive measurements of viral burden (reflecting rapid or unchecked viral replication) may be useful in assessing HIV disease stage, disease progression, response

Infants born to mothers who are infected with the human immunodeficiency virus (HIV) may or may not become infected by perinatal transmission. Unfortunately, passively transferred maternal antibodies make it hard to determine the infant's infection status from HIV antibody testing, because shortly after birth it is not possible to distinguish passively transferred maternal antibodies from antibodies produced by an infected infant. Usually, the infection status is unobservable for each infant, unless the infant reaches the age of 15 months or develops an HIV-related disease such as the acquired immunodeficiency syndrome (AIDS). Traditionally, statistical analyses of the perinatal transmission rate of HIV are based on infants who had been born at least 15 months before the date of analysis. Such analyses can be both inefficient and biased. In this note, we define a mixture model underlying the onset time of AIDS and then obtain the nonparametric maximum likelihood estimators of the HIV transmission rate and of the distribution function of AIDS onset time for infected infants. Nonparametric tests are also derived for detecting differences in HIV transmission rates among different groups of infants. Finally, the methods are applied to the Mothers and Infants Cohort Study in New York City. The transmission rate of HIV from infected mothers to their infants was estimated to be 30.0% with 95% confidence interval (22.3%, 39.1%).

A flow cytometry-based assay for detection of immunoglobulin (Ig) class and subclass antibodies in human serum or plasma was developed. With use of this procedure, the presence and relative frequency of antibody activity in the Ig classes and subclasses (IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, and IgM) to human immunodeficiency virus type 1 (HIV-1) proteins (gp160, gp120, p66, and p24) was determined in serum or plasma from a cohort of 47 HIV-1-infected, pregnant women. Antibody activity in each of the classes and subclasses was found with differences in frequency depending on the Ig class/subclass and the HIV-1 protein. IgG1 antibodies were the most frequently reactive Ig class/subclass to each protein. Intermediate frequencies of reactivity were found in IgA1, IgG2, IgG3, and IgM class and subclasses and antibodies of the IgA2, IgE, and IgG4 class/subclass the least frequently detected. An unexpected finding was the presence of IgD antibodies to HIV-1 proteins in approximately 50% of the individuals. The distributions of Ig class/subclass antibodies to the different HIV-1 proteins were compared in sera from 14 mothers giving birth to infants who were determined to be HIV-1 infected with sera from 25 individuals whose infants were not infected. Sera from transmitting mothers contained a broader distribution of class and subclass antibodies compared to sera from nontransmitting women. The single most frequent antibody-antigen combination that was found in the transmitting mother was IgG2-gp160.(ABSTRACT TRUNCATED AT 250 WORDS)

The resurgent tuberculosis epidemic represents--especially in New York City--a failure to maintain a public health infrastructure that was focused on preventing active disease in high-risk populations (i.e., individuals with the human immunodeficiency virus [HIV]) and on treating active tuberculosis patients until cured. Although the tuberculosis problem in New York City and other localities is worsened by homelessness, poverty, and substance abuse, it is possible to bring tuberculosis under control by directing public health resources into targeted programs that enhance compliance with tuberculosis treatment regimen and expand chemoprophylaxis efforts among HIV-infected individuals. These two avenues will decrease, respectively, the number of cases of multidrug-resistant tuberculosis and the total number of new cases.

Objectives. To define the spectrum of HIV-1 -related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. Design and methods. The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. Results. Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts < 200 x 106/I than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts < 500 x 106/I, of whom 41 had CD4 counts < 200 x 106/I; thus, in addition to an estimated 16425 individuals living with AIDS in NYC, we estimate that there are at least 14454 HIV-infected individuals without AIDS with CD4 counts < 500 x 106/I, of whom 6734 have CD4 counts < 200 x 106/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. Conclusions. These data indicate that there are more than 30000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.

From October 1987 to June 1988, we attempted to determine the prevalence of HIV infection among patients hospitalized with tuberculosis and the extent of immunosuppression among those tuberculosis patients infected with HIV. Of 178 consecutive patients, 18-65 years of age, who were hospitalized with newly diagnosed, previously untreated tuberculosis, 46% (82 out of 178) had clinical or serological evidence of HIV infection, 30% (54 out of 178) were HIV-seronegative, and 24% (42 out of 178) could not be assessed for the presence of HIV infection. Among the HIV-seropositive patients without an AIDS-defining diagnosis by non-tuberculous criteria, the median CD4 lymphocyte (CD4) count was 133 x 10(6) cells/l (range: 11-677 x 10(6]; among the HIV-seronegative patients, the median CD4 count was 613 x 10(6) cells/l (range: 238-1614 x 10(6); P less than 0.001). Among the HIV-seropositive patients, those with disseminated tuberculosis (median CD4 = 79 x 10(6) cells/l) and those with pulmonary tuberculosis who had radiographic evidence of mediastinal or hilar adenopathy (median CD4 = 45 x 10(6) cells/l) had the most severe CD4 depletion, whereas those with localized extrapulmonary tuberculosis (median CD4 = 242 x 10(6) cells/l) and those with pulmonary tuberculosis without adenopathy (median CD4 = 299 x 10(6) cells/l) were less severely immunosuppressed. Of the 178 patients, 6% (11 out of 178) were infected with strains of Mycobacterium tuberculosis resistant to both isoniazid and rifampin.

I was asked by Dr David Price to speak about the topic of assuring and calming a nervous public. The problem I was asked to address can be stated as follows: How can one develop a policy that (1) is scientifically rational; (2) protects the public; (3) protects the infected from discrimination; and (4) does not lead to undesirable derivative consequences, such as testing of all health care workers and patients. This charge is difficult in ordinary circumstances. The fear of acquiring human immunodeficiency virus (HIV) disease from a health care provider makes the task all the more difficult. I have no answers to the question of "what should our policy be concerning HIV-infected health care workers?" I can only offer some observations and vignettes from policy debates of the past. They may provide useful guideposts for the current discussion. My observations are influenced by past experience with the acquired

Fifty-six human immunodeficiency virus seropositive-women and 76 human immunodeficiency virus seronegative-women had known CD4 cell values and were followed up throughout pregnancy. The women with seronegative results and the 40 with seropositive results and CD4 (helper cell) counts consistently greater than 300 cells/mm3 had no serious infections during pregnancy. Among the 16 with seropositive results and counts that fell below 300 cells/mm3, three developed opportunistic infections, one had pneumonia, and one had a post-cesarean-section abscess. Human immunodeficiency virus seropositive-women with low CD4 counts are at markedly increased risk of serious infections during pregnancy. The consequences of this for fetal health, pregnancy management, maternal well-being, and human immunodeficiency virus testing policies are discussed.

With the aim of achieving earlier diagnosis of human, immunodeficiency virus (HIV) infection in infants, IgA and IgM HIV antibodies in serum samples from babies born to seropositive mothers were assayed by immunoblot and enzyme-linked immunosorbent assay after removal of IgG with recombinant protein G. 64 samples were from 38 HIV-infected babies with Centers for Disease Control classifications of P1 or P2. Among these infected children IgA HIV antibodies were present in all 23 samples from those older than 12 months, in 12 of 18 samples from babies aged 6-12 months, in 5 of 10 samples from babies aged 3-5 months, and in 2 of 13 from babies under 3 months old. The 6 IgA-negative samples from infants over 6 months were all from infants with severe AIDS and/or hypogammaglobulinaemia. IgA HIV antibodies were present in twice as many samples as IgM HIV antibodies (66% vs 33%). No IgM or IgA HIV antibodies were detected in infants who subsequently seroreverted or in infants born to seronegative mothers. The correlation of the serological results with clinical information on each child suggests that detection of IgA HIV antibodies is an effective method for early diagnosis of HIV-infected infants without signs of infection.

The number of intravenous drugs users (IVDUs) developing end-stage renal disease at our institution increased 400% between 1981 and 1987. During this period the total number of IVDUs in our catchment area remained stable and referral patterns to our hospital were unchanged. A serologic, clinical and risk-factor survey for HIV infection was conducted in our maintenance hemodialysis unit with the objective of evaluating the interrelationship between HIV infection and the increasing incidence of renal failure in IVDUs. The risk of nosocomial transmission of HIV in a hemodialysis unit with an expected high prevalence of infection was also investigated. The effect of HIV seropositivity on the clinical course of patients receiving maintenance hemodialysis was evaluated prospectively. Twenty-seven (39%) out of 70 maintenance hemodialysis patients tested were seropositive for HIV. Twenty-three (88%) out of 26 IVDUs receiving dialysis were seropositive for HIV. Despite marked CD4 cell depletion (mean CD4 cell count 225), none of the seropositive patients had AIDS when first evaluated and only one developed AIDS during 12 months of follow-up. None of the dialysis staff members or dialysis patients without HIV risk factors was seropositive for HIV. IVDUs who develop end-stage renal disease appear to have a high rate of infection with HIV. We can expect that the number of HIV-infected dialysis patients will continue to increase. Fortunately, even in a high prevalence hemodialysis unit, the risk of nosocomial transmission of HIV appears to be low.