Incidence and factors associated with extrapulmonary cryptococcosis among persons with HIV infection in Los Angeles County.

OBJECTIVE: To determine the incidence and factors associated with extrapulmonary cryptococcosis among a cohort of persons with HIV in Los Angeles County. DESIGN: Records-based cohort study. METHODS: Data were analysed from a cohort of 3836 persons aged > or = 13 years with HIV infection enrolled from four outpatient facilities in Los Angeles from 1990 to 1995. The potential association between cryptococcosis and demographic risk behavior and clinical factors was assessed. Possible seasonal clustering was evaluated and an estimate of survival following cryptococcosis was calculated. Multivariate analysis was performed using a Cox proportional hazards approach. RESULTS: Cryptococcosis was identified in 112 patients (2.9%) representing a crude incidence rate of 1.7 cases per 100 person-years experience. The rate of cryptococcosis was higher among men than women (1.9 and 0.6, respectively; P < 0.01) and in Hispanics than in whites (2.3 and 1.2, respectively, P < 0.01). A significant trend of decreasing cryptococcosis was observed with increasing age (P < 0.01). Cryptococcosis increased with declining CD4+ lymphocyte count, with risk being greatest at CD4+ cell counts below 100 x 10(6)/l (P < 0.001). In bivariate analysis persons with a history of antifungal medication had a marginally lower rate of cryptococcosis, but this difference was not statistically significant. The rate of cryptococcosis was significantly higher in fall and winter months [rate ratio (RR), 1.45; 95% confidence interval (CI), 1.0-2.3; P = 0.05]. After controlling for other variables, cryptococcosis was more common in men than women (adjusted RR, 3.2; 95% CI, 1.0-10.4) and in Hispanics than whites (adjusted RR, 1.6; 95% CI, 0.9-2.7). Both CD4+ count and age continued to be strongly associated with the occurrence of cryptococcosis. After controlling for other factors a substantial protective effect was observed for antifungal therapy (adjusted RR, 0.48; 95% CI, 0.29-0.79). CONCLUSION: Our data suggest that HIV-infected men, Hispanics, persons aged under 45 years and those with CD4+ counts under 100 x 10(6)/l have an increased risk of extrapulmonary cryptococcosis. A fall-winter seasonality in the occurrence of cryptococcosis may exist. Significant primary protection against cryptococcal disease is afforded by antifungal therapy. These results may provide insight into possible routes of transmission and sources of cryptococcal infection and help guide both primary prophylaxis and early recognition and diagnosis in persons likely to be at increased risk.

Effect of menstrual cycle on HIV-1 levels in the peripheral blood and genital tract. WHS 001 Study Team.

OBJECTIVE: To assess the variation in HIV-1 over the menstrual cycle, including RNA levels in the female genital tract, plasma HIV-1-RNA levels, CD4 cell counts, and culturable virus. DESIGN: A prospective analysis of 55 HIV-1-infected women. METHODS: Blood and genital tract specimens were collected weekly over 8 weeks, spanning two complete menstrual cycles. Applying repeated-measures models that used menses as the reference level, the variation in viral RNA levels was compared in endocervical canal fluid and cells (collected by Sno-strips and cytobrush, respectively) and ectocervicovaginal lavage (CVL) fluid. Repeated-measures models were also used to assess the variation in plasma CD4 cell counts and viral load. RESULTS: Shedding patterns differed among the three sampling methods, independent of genital tract co-infections. Genital tract HIV-1-RNA levels from CVL fluid and endocervical canal cytobrush specimens were highest during menses and lowest immediately thereafter (P = 0.001 and P = 0.04). The HIV-1-RNA level in endocervical canal fluid was highest in the week preceding menses (P = 0.003). The menstrual cycle had no effect on blood levels of RNA (P = 0.62), culturable virus (P = 0.34), or CD4 cell counts (P = 0.55). HIV-1-RNA levels were higher in endocervical canal fluid than in peripheral blood plasma during the late luteal phase (P = 0.03). CONCLUSION: HIV-1-RNA levels vary with the menstrual cycle in the female genital tract but not the blood compartment. HIV-1-RNA levels are higher in endocervical canal fluid than in blood plasma. These findings may have important implications for sex-specific pathogenesis, heterosexual transmission, and contraceptive hormone interventions in HIV-1-infected women.

Incorporation of zidovudine into leukocyte DNA from HIV-1-positive adults and pregnant women, and cord blood from infants exposed in utero.

OBJECTIVE: The nucleoside analog 3'-azido-3'-deoxythymidine (ZDV) has widespread clinical use but also is carcinogenic in newborn mice exposed to the drug in utero and becomes incorporated into newborn mouse DNA. This pilot study was designed to determine ZDV incorporation into human blood cell DNA from adults and newborn infants. DESIGN: In this prospective cohort study, peripheral blood mononuclear cells (PBMC) were obtained from 28 non-pregnant adults and 12 pregnant women given ZDV therapy, six non-pregnant adults with no exposure to ZDV, and six non-pregnant adults who last received ZDV > or = 6 months previously. In addition, cord blood leukocytes were obtained from 22 infants of HIV-1-positive, ZDV-exposed women and from 12 infants unexposed to ZDV. There were 11 mother-infant pairs involving HIV-1 -positive women. METHODS: DNA was extracted from PBMC obtained from non-pregnant HIV-1-positive adults taking ZDV, pregnant HIV-1-positive women given ZDV during pregnancy, and from adults not taking ZDV. Cord blood leukocytes were examined from infants exposed to ZDV in utero and from unexposed controls. DNA samples were assayed for ZDV incorporation by anti-ZDV radioimmunoassay (RIA). RESULTS: The majority (76%) of samples from ZDV-exposed individuals, pregnant women (8 of 12), non-pregnant adults (24 of 28), or infants at delivery (15 of 22), had detectable ZDV-DNA levels. The range of positive values for ZDV-treated adults and infants was 25-544 and 22-452 molecules ZDV/10(6) nucleotides, respectively. Analysis of 11 mother-infant pairs showed variable ZDV-DNA incorporation in both, with no correlation by pair or by duration of drug treatment during pregnancy. Two of the 24 samples from individuals designated as controls were positive by anti-ZDV RIA. The 20-fold range for ZDV-DNA values in both adults and infants suggested large interindividual differences in ZDV phosphorylation. CONCLUSIONS: Incorporation of ZDV into DNA was detected in most of the samples from ZDV-exposed adults and infants. Therefore, the biologic significance of ZDV-DNA damage and potential subsequent events, such as mutagenicity, should be

Seroepidemiologic studies of cytomegalovirus and Epstein-Barr virus infections in relation to human immunodeficiency virus type 1 infection in selected recipient populations. Transfusion Safety Study Group.

Antibodies to human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were evaluated among 1,171 persons with and without antibodies to human immunodeficiency virus type 1 (anti-HIV-1). These included 97 blood donors, 577 persons given blood components or products, and 497 controls. A significantly higher proportion of anti-HIV-1 positive than -negative donors were anti-CMV-positive, a finding associated with homosexual contact among some of the former. Among subjects with treated clotting disorders, there was no difference in prevalence of anti-CMV or anti-EBV between anti-HIV-1-positive and -negative persons. The prevalence of antibodies to EBV early antigens showed no relationship to anti-HIV-1 status. Anti-CMV positivity in anti-HIV-1-negative donors was associated with an increase in mean CD8 counts and lower mean CD4/CD8 ratio. Anti-CMV and anti-EBV positivity in anti-HIV-1-positive subjects with treated clotting disorders was not associated with a lower CD4 or higher CD8 count than HIV-1 infection alone. Subjects who developed AIDS after enrollment had no significant difference in median time from entry to diagnosis when analyzed by serologic evidence of CMV and EBV antibody status at entry, and a few subjects had AIDS at entry without serologic evidence of prior CMV or EBV infection. The overall results are consistent with acquisition and progression of HIV-1 independently of coincident CMV or EBV infection.

Incidence and determinants of Pseudomonas aeruginosa infection among persons with HIV: association with hospital exposure.

BACKGROUND: Little information exists on risk factors for Pseudomonas aeruginosa infection in persons with HIV. We assessed the incidence and factors associated with P aeruginosa among persons with HIV enrolled in a large observational cohort study in Los Angeles. METHODS: Data were analyzed from 4825 persons aged > or =13 years with HIV infection enrolled from 4 outpatient facilities from 1990 to 1998. The association between P aeruginosa infection and demographic, risk behavior, and clinical factors was assessed. RESULTS: P aeruginosa was diagnosed in 72 (1.5%) patients representing a crude incidence rate of 0.74 per 100 person-years. The most frequent site of infection was pulmonary (47%). In multivariate analysis, prior hospitalization (adjusted rate ratio = 7.9, 95% CI, 3.8-16.2), and both dapsone (adjusted rate ratio = 4.0, 95% CI, 2.2-7.4) and trimethoprim-sulfamethoxazole (adjusted rate ratio = 2.5, 95% CI, 1.2-5.3) use were independently associated with higher rates of infection. Increasing days of inpatient stay (P <.01) and decreasing CD4(+) counts (P <.01) were strongly associated with P aeruginosa. Azithromycin use decreased the risk of infection by nearly 70%. CONCLUSION: Although the overall observed incidence of P aeruginosa was low, hospital exposure, declining CD4(+) levels, and the use of dapsone or trimethoprim-sulfamethoxazole increased the risk of P aeruginosa disease, and azithromycin use was protective in this population. These findings may assist in the early recognition and diagnosis of persons likely to be at increased risk of P aeruginosa infection.

Incorporation of zidovudine into cord blood DNA of infants and peripheral blood DNA of their HIV-1-positive mothers.

The nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) is a weak carcinogen in adult female mice and a moderately strong carcinogen in the offspring of female mice given the drug during gestation. In addition, incorporation of AZT into DNA was observed in multiple organs of transplacentally exposed newborn mice. Here we investigate the incorporation of AZT into peripheral leukocyte DNA of HIV-1-positive adult pregnant women given AZT for variable times during gestation and cord blood of infants exposed to AZT in utero. The length of treatment varied between 10 days and 9 months. High molecular weight DNA was extracted from maternal peripheral blood mononuclear cells (PBMC) and infant cord blood. A specific AZT-DNA radioimmunoassay was used to determine the amount of AZT incorporated into leukocyte DNA. Incorporation of AZT into DNA ranged up to 183.3 and 344.5 molecules of AZT/10(6) nucleotides in the mothers and infants, respectively, and was detected in about 70% of samples. Therefore, AZT-induced mutagenic events are possible in the majority of adults and infants. No correlation was found between level of incorporation and length of AZT treatment, suggesting that the differences observed among the individuals arise from variability in AZT metabolism. These data support previous observations that a high degree of inter-individual variability in AZT phosphorylation occurs in primates.

Seasonality and factors associated with cryptosporidiosis among individuals with HIV infection.

The seasonality and factors associated with Cryptosporidium infection were assessed in a cohort of HIV-infected patients in Los Angeles County to better define the epidemiology of cryptosporidiosis among individuals with HIV. Data were analysed from a cohort of 4247 patients > or = 13 years of age with HIV infection enrolled from four outpatient facilities in Los Angeles, 1990-6. Cryptosporidiosis was diagnosed in 120 (2.8%) patients. Among the 1296 individuals with complete follow-up until death, cryptosporidiosis occurred in 69 (5.3%). The seasonal rate of cryptosporidiosis showed a modest bimodal trend with the highest rates occurring in March-May and September-October. There was no difference in the rate of cryptosporidiosis for the periods of heaviest rainfall (December-March) and low rainfall (April-November). Infection rates were higher among males (1.59 per 100 person-years) than females (0.92) and lower in blacks (0.98) than other racial/ethnic groups (1.80). A significant trend of decreasing cryptosporidiosis was observed with increasing age, with the highest rate (2.34) in the 13-34 year age group. A strong association between cryptosporidiosis and CD4+ count was noted. These data suggest that cryptosporidiosis among HIV-infected individuals in Los Angeles County exhibits a modest spring and fall seasonality. This pattern of occurrence of cryptosporidiosis appears temporally unrelated to local rainfall patterns. Our findings suggest that HIV-infected men, individuals in younger age groups and those with CD4+ lymphocyte counts < 100 x 10(6)/l are at increased risk of cryptosporidiosis. Blacks with HIV infection appear less likely than other racial/ethnic groups to be diagnosed with Cryptosporidium infection. These results may provide insight into possible routes of transmission and sources of cryptosporidiosis infection in individuals with HIV.

Cryptococcosis in the acquired immunodeficiency syndrome.

The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7. Meningitis was the commonest clinical feature (18 patients). Blood cultures and serum cryptococcal antigen were frequently positive. In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive. Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy. Standard courses of amphotericin B alone or combined with flucytosine were ineffective. Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.