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HIV seroprevalence was previously found to be 9-11% among the urban homeless in San Francisco, with most infections among injection drug users, men who have sex with men, and those who exchange sex for money or drugs. In this study, HIV incidence and risk factors for seroconversion were estimated among persons who repeatedly participated in cross-sectional serosurveys over a period of 10 years. There were 6 seroconversions among 799 HIV-negative persons, for an incidence rate of 0.30% per person-year (95% CI: 0.12-0.61% per person-year). The seroconversion rate among men who had had recent sex with men was 1.22% per person-year (95% CI: 0.29-3.18) and was 0.52% per person-year (95% CI: 0.19-1.13% per person-year) among those who ever injected drugs. The seroconversion rate among those who were aged <30 years at baseline was 1.67% per person-year (95% CI: 0.40-4.36% per person-year), which was significantly higher than for those age > or =30 years. Policy implications are that HIV resources aimed at the more stable, older homeless population should probably focus on treatment, while prevention efforts, conversely, should probably be targeted to younger homeless persons.

Background: The prevalence of vancomycin-resistant enterococci (VRE) is increasing, despite infection control measures. Limited data link ticarcillin-clavulanate to higher VRE prevalence., Methods: Active surveillance for VRE was conducted before and after a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam. Rectal swabs were obtained serially in 863 adult patients admitted to intensive care units (ICUs) between November 1, 2000 and September 30, 2004., Results: In the postswitch period, 38 of 497 (7.6%) patients acquired VRE versus 42 of 366 (11.5%) patients in the preswitch period. Survival analysis showed an overall hazard ratio (HR) of .68 postswitch versus preswitch ( P = .07), with the greatest change in the surgical ICU (HR = .17, P = .006). Multivariate analysis showed an overall HR = .51 ( P = .004). Hospital-wide, nonstool VRE clinical cultures fell from 39 (.58/1000 patient days) in the 10-month preswitch period to 27 (.33/1000 patient days) in the 12-month postswitch period. Infection control practices and use of other antibiotics remained stable., Conclusions: VRE acquisition appeared to decrease in association with a formulary change from ticarcillin-clavulanate to piperacillin-tazobactam.

To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the community and their population dynamics, we studied the molecular epidemiology of a random sample (n=490) from a collection of 2154 inpatient and outpatient MRSA isolates during a 7-year period in San Francisco. We noted a progressive replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing isolates with type IV SCCmec-bearing isolates, which coincided with >4-fold increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing isolates involved in the increase in methicillin resistance belonged to 4 molecular genotypes. These 4 genotypes were associated predominantly with community-onset disease, rather than hospital- or long-term-care facility-onset disease (76.9% vs. 19.4% vs. 3.7%; P=.0005), suggesting that they are not feral descendants of hospital isolates. The longitudinal results linked the dramatic increase in MRSA infections to an expanding community reservoir of MRSA genotypes with intrinsic community survival advantage.

Background: We examined adherence to highly active antiretroviral therapy (HAART) in the homeless population, a population thought to be at high risk for poor adherence to therapy and for development of drug-resistant strains of human immunodeficiency virus (HIV)., Methods: We performed a 12-month prospective study of 148 persons receiving HAART who were identified in a stratified screening of the homeless and marginally housed. We sampled in lunch lines, shelters, and hotels in 3 neighborhoods of San Francisco, California. We used pill counts at unannounced home visits as the primary measure of adherence., Results: Of 148 individuals sampled, 46 (31%) discontinued HAART during the study. Average adherence in the group of those who discontinued HAART was 51%, and 9% of these subjects had undetectable virus loads (i.e., <400 copies/mL) at the last follow-up visit. Predictors of discontinuation of therapy were depressive symptoms, injection drug use, African American ethnicity, and early poor adherence. Of 148 subjects, 102 (69%) continued to receive HAART throughout the study period. Average adherence in the group of those who continued to receive HAART was 74%, and 55% of these subjects had undetectable virus loads at the last follow-up visit. Predictors of lower average adherence in this group were African American ethnicity and use of crack cocaine; men who had sex with men had higher adherence., Conclusions: One-third of homeless and marginally housed persons receiving HAART discontinued therapy during the follow-up period and would benefit from adherence interventions directed at sustaining therapy; two-thirds continued to receive therapy at adherence levels comparable to those found with other clinical populations.

Hypothesis: A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in soft tissue infections presents a treatment challenge., Design: Retrospective analysis., Setting: The San Francisco General Hospital Integrated Soft Tissue Infection (ISIS) Clinic., Patients: Patients treated at the ISIS Clinic from July 1, 2000, to June 30, 2003., Main Outcome Measures: Information on patient demographics, surgical procedures, microbiologic studies, and antibiotic treatments was obtained for all patients treated in the ISIS Clinic. Microbial data and antibiotic susceptibility pattern of S aureus, treatment outcome, and antibiotic prescribed were analyzed for all evaluable patients., Results: The ISIS Clinic treated 6156 unique patients for 12,012 episodes of infection. In this cohort, 5164 (84%) were either homeless or had no health insurance. More than half of the patients (58%) were injection drug users, but most had only 1 prior visit to the clinic (62%). Patients underwent a surgical procedure 7707 times (64%). Of the 837 positive cultures obtained, S aureus was recovered 695 times (83%), and 525 (63%) of the cultures contained MRSA. Therefore, a full 76% of all S aureus isolated was MRSA. In a subset analysis of 622 cultures collected prospectively from consecutive patients, 282 (45%) grew organisms, of which 256 (91%) were S aureus. MRSA represented 59% of all S aureus isolated. Homelessness and injection drug use were risk factors for infection by S aureus and MRSA. In another subgroup of patients with soft tissue infections that required admission to the hospital, MRSA was recovered from the cultures in 149 patients. In these patients with MRSA, 44 (30%) only received a beta-lactam antibiotic, inactive against MRSA, and had full resolution of their infection., Conclusions: The prevalence of MRSA soft tissue infections in the medically underserved ISIS Clinic cohort is extremely high. The transmission of the MRSA seems to be in the community. Antibiotic therapy directed at MRSA may not be needed in a large number of patients with these soft tissue infections. Studies to identify the source and cause of this MRSA outbreak are urgently needed. Clinical trials to examine the need for antibiotic therapy in soft tissue infections should be conducted.

Background: There are no validated measures of adherence to HIV antiretroviral therapy in resource-poor settings. Such measures are essential to understand the unique barriers to adherence as access to HIV antiretroviral therapy expands., Methods: We assessed correspondence between multiple measures of adherence and viral load suppression in 34 patients purchasing generic Triomune antiretroviral therapy (coformulated stavudine, lamivudine, and nevirapine; CIPLA, Ltd., Mumbai, India) in Kampala, Uganda. Measures included 3-day patient self-report, 30-day visual analog scale, electronic medication monitoring, and unannounced home pill count. HIV-1 load was determined at baseline and 12 weeks., Results: Mean adherence was 91%-94% by all measures. Seventy-six percent of subjects had a viral load of <400 copies/mL at 12 weeks. All measures were closely correlated with each other (R = 0.77-0.89). Each measure was also significantly associated with 12-week HIV load. There was no significant difference between patient-reported and objective measures of adherence., Conclusions: This sample of patients purchasing generic HIV antiretroviral therapy has among the highest measured adherence reported to date. Patient-reported measures were closely associated with objective measures. The relative ease of administration of the 30-day visual analog scale suggests that this may be the preferred method to assess adherence in resource-poor settings.

Objectives: We report HIV seroprevalence and risk factors for urban indigent adults., Methods: A total of 2508 adults from shelters, meal programs, and low-cost hotels received interviews, blood tests, and tuberculosis screening., Results: Seroprevalence was 10.5% overall, 29.6% for men reporting sex with men (MSM), 7.7% for non-MSM injection drug users (IDUs), and 5.0% for residual non-MSM/non-IDUs. Risk factors were identified for MSM (sex trade among Whites, non-White race, recent receptive anal sex, syphilis), non-MSM IDUs (syphilis, lower education, prison, syringe sharing, transfusion), and residual subjects (> or = 5 recent sexual partners, female crack users who gave sex for drugs)., Conclusions: HIV seroprevalence was 5 times greater for indigent adults than in San Francisco generally. Sexual behavior predicted HIV infection better than drug use, even among IDUs.

The standard view postulates a bell-shaped relationship between adherence to therapy and development of drug-resistant human immunodeficiency virus (HIV), with a resistance peak at a moderate level of adherence. This relationship has not been confirmed empirically. We statistically modeled the relationship between adherence and development of drug resistance, using empirically defined relationships of the rate of viral suppression and drug-resistance-mutation accumulation derived from patients receiving protease-inhibitor-based therapy. We found that the maximal rate of drug resistance occurs at 87% adherence and declines modestly at 100% adherence. Higher levels of viral suppression at 100% adherence (a marker of greater regimen potency) progressively reduce the overall population rate of drug resistance and shift the peak resistance rate to lower levels of adherence.

To characterize methicillin-resistant Staphylococcus aureus (MRSA) strains circulating in the community, we identified predictors of isolating community MRSA and genotyped a sample of MRSA collected from a community-based, high-risk population. Computerized databases of the Community Health Network of San Francisco and the Clinical Microbiology Laboratory were searched electronically for the years 1992-1999 to identify community-onset infections caused by MRSA. Sequential analyses were performed to identify predictors of MRSA strains. The majority (58%) of infections were caused by strains traceable to the hospital or to long-term care facilities. Injection drug use was associated with infections that were not associated with health care settings. Genotypes for 20 of 35 MRSA isolates recovered from injection drug users did not match any of >600 genotypes of clinical isolates. In a nonoutbreak setting, the hospital was the main source of community MRSA; however, the presence of genetically distinct and diverse MRSA strains indicates MRSA strains now also originate from the community.

Objective: To measure Hepatitis C Virus (HCV) prevalence, incidence, and initiation of HCV therapy in a representative HIV-infected cohort of the urban poor., Design: Cohort analysis., Setting: The Research and Access to Care for the Homeless (REACH) Cohort is a systematic sample of HIV-infected marginally housed individuals identified from single-room occupancy hotels, homeless shelters, and free lunch programs in San Francisco., Participants: Two hundred forty-nine participants with 28.9 months (median) of follow-up were studied. Mean age was 44 (range 24 to 75, standard deviation 8.4) years. Eighty-two percent were male, 43% were African-American, 64% were lifetime injection drug users, and 24% had been on the street or in a shelter in the prior month., Interventions: We measured HCV testing and treatment history with structured interviews; additionally, participants were tested for HCV antibodies (EIA-2) with RNA viral load confirmation., Main Results: At baseline, 172 (69.1%) were HCV-positive and 182 (73.1%) were HCV-positive at follow-up, including 155 (62.2%) with viremia. HCV-positive status was associated with having injected drugs, elevated serum alanine aminotransferase, homelessness in the last 1 year, and more severe depressive symptoms. The incidence of new HCV infection was 4.63% per person-year (ppy; 95% confidence interval, 2.31 to 8.13) in the entire cohort and 16.77% ppy among injection drug users. The prevalence of HCV antibody-negative HCV-viremia was 13.2% (10/76). Nonwhites were less likely to receive HCV testing and subspecialty referral, controlled for drug use and other confounders. Sixty-eight percent (123/182) were aware treatment was available; however, only 3.8% (7/182) or 1.16% ppy received HCV treatment., Conclusions: While HCV infection is common, HCV treatment is rare in the HIV-HCV coinfected urban poor. Urban poor, nonwhite individuals are less likely to receive HCV testing and subspecialty referral than their white counterparts. Antibody-negative infection may complicate screening and diagnosis in HIV-infected persons. J

Purpose: To examine the performance of an instrument to assess adherence based on a visual analogue scale, compared to an instrument based on 3-day recall, using unannounced pill counts in the place of residence as the gold standard., Method: We prospectively assessed adherence to antiretroviral therapy in 84 marginally housed indigent HIV-infected patients who were receiving stable antiretroviral therapy in San Francisco, California, with three adherence assessments over no more than 4 months., Results: Mean adherence using the visual analogue scale, 3-day recall, and unannounced pill count methods were 82.5%, 84.2%, and 75.9%, respectively. The correlation between visual analogue scale and unannounced pill count was high (r = 0.76) and was not statistically different from that between 3-day recall and unannounced pill count (r = 0.71; p =.52). Both methods were also similarly inversely correlated with HIV viral load (r = -0.49 and -0.34, respectively; p =.22 for the difference in the correlations). The visual analogue scale correlation with unannounced pill count was stable over time and remained high in all subpopulations examined., Conclusion: A visual analogue scale to assess adherence was performed as well as a more complicated 3-day recall instrument in this diverse population. Given its simplicity, the visual analogue scale adherence instrument will be useful in research and may be useful in routine patient care.

We examined cross-sectionally the relationship between untimed drug levels and adherence in 83 individuals. Abnormally low untimed antiretroviral drug levels were sensitive in identifying individuals adherent to 60% or less of medication doses over 3 - 5-week period. An abnormally low drug level was associated with a higher viral load. A single abnormally low untimed antiretroviral drug level can identify an individual with very low adherence at high risk of HIV disease progression and death.

Staphylococcus aureus clinical isolates obtained from patients who were inmates of the San Francisco County jail system showed an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) from 29%, in 1997, to 74%, in 2002; 91% of the MRSA isolates carried staphylococcal chromosomal cassette mec (SCCmec) type IV. Pulsed field gel electrophoresis and multilocus sequence typing demonstrated 2 major clonal groups. One of these clonal groups is genetically indistinguishable from the strain responsible for an outbreak of MRSA in the Los Angeles County jail system in 2002.

Objectives: To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence., Methods: Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2., Results: High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92-100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79-100%)., Conclusion: Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.

Background: We report our experience in a county hospital with the use of selective contact isolation for patients with vancomycin-resistant Enterococcus faecium (VREF). About 12% of patients with VREF are isolated for reasons such as draining wounds and uncontrolled diarrhea., Methods: Passive surveillance identified all inpatients (181) from 1995 to 1999 with cultures positive for VREF. Data were collected via electronic databases and from prospectively maintained infection control records. Isolates were typed with use of pulsed-field gel electrophoresis., Results: Nearly all patients (175/181) with VREF had been admitted at least 48 hours or had a history of previous hospitalization. Most patients (69%) had urine cultures positive for VREF without blood cultures positive for the organism. Only 12 of 127 (9.%) patients with complete data had VREF infection on the basis of receiving treatment and/or having more than 1 blood culture positive for VREF. After VREF became endemic, statistically significant increased prevalence was not detected via surveillance of clinical cultures nor sequential point-prevalence studies. Two major genotypes carrying vanB resistance genes were identified and persisted throughout the period studied. VREF persisted in individual patients up to 46 months., Conclusions: The number of VREF infections in this facility has been low, despite appreciable colonization, for an extended period during which selective isolation was used.

The study objective was to determine the prevalence and risk factors for nasal colonization with Staphylococcus aureus and methicillin resistance among the urban poor and to compare antibiotic resistance and genetic similarity to concurrently collected clinical isolates of methicillin-resistant S. aureus (MRSA). A population-based community sample of 833 homeless and marginally housed adults were cultured and compared with 363 clinical isolates of MRSA; 22.8% of the urban poor were colonized with S. aureus. Of S. aureus isolates, 12.0% were methicillin resistant. Overall prevalence of MRSA was 2.8%. Significant multivariate risk factors for MRSA were injection drug use (odds ratio [OR], 9.7), prior endocarditis (OR, 4.1), and prior hospitalization within 1 year (OR, 2.4). Resistance to antimicrobials other than beta-lactams was uncommon. Only 2 individuals (0.24%) with MRSA had no known risk factors. A total of 22 of 23 community MRSA genotypically matched clinical MRSA isolates, with 15 of 23 isolates identical to MRSA clones endemic among hospitalized patients.

Background: Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance., Methods: Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed., Findings: 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041)., Interpretation: Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.

Background: Adherence assessment is an essential component of monitoring HIV antiretroviral therapy. Prior studies suggest that medical providers frequently estimate individual patient adherence inaccurately., Objective: We compared provider estimates of nonadherence to antiretroviral therapy with unannounced pill counts and structured patient interviews to determine the accuracy of adherence information obtained by providers and patients., Design, Setting, and Participants: Comparison of three adherence measures in homeless or marginally housed persons receiving HIV antiretroviral therapy (n = 45) and their providers (n = 35)., Measurements: Provider estimate of percentage of pills taken; three successive patient structured reports of number of doses missed in the last 3 days; and three successive unannounced pill counts., Results: 13% (95% confidence interval [CI], 4%-22%) of patients were not following their regimen as directed. Provider-adherence estimate explained only 26% (95% CI, 6%-47%) of the variation in pill count adherence, whereas patient report explained 72% (95% CI, 52%-96%). The sensitivity and specificity of provider estimates of nonadherence, defined as <80% of pills taken by pill count, were 40% and 85%, respectively. The sensitivity and specificity of patient interview were 72% and 95%, respectively., Conclusions: Provider estimate of adherence was inaccurate whereas structured patient report was more closely related to pill count. Structured assessment over several short intervals may improve accuracy of adherence assessment in clinical practice.

Advances in biomedical research have resulted in new standards for HIV treatment that involve earlier intervention with more complex combination antiretroviral therapy. This article examines the implications of these treatments for federally funded programs that provide HIV care and discusses mechanisms for making Medicaid and the AIDS Drug Assistance Program (ADAP) consistent with the treatment standards. The article provides a rationale for expanding access by expanding entitlement programs (Medicaid) rather than discretionary programs (ADAP). A potential legislative approach to Medicaid expansion is described. Cost projections suggest that this approach is feasible and would constitute a significant step toward increasing access to HIV care.

Objective: To examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy., Design and Setting: A cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels., Participants: Thirty-four HIV-infected people with a median of 12 months of PI therapy., Main Outcomes: Adherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance., Results: Median adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirty-eight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36-65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P < 0.03)., Conclusion: A substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.

The humoral response to a herpes simplex virus (HSV) type 2 subunit vaccine containing recombinant glycoproteins B (gB2) and D (gD2) was tested in 3 groups of patients. These included HSV-seronegative, HSV-1-seropositive, and HSV-2-seropositive individuals. There were excellent antibody responses, as measured by gB2- and gD2-specific ELISAs and HSV-2 neutralization assays. However, in 2 HSV-2 antibody-dependent cellular cytotoxicity (ADCC) assays, there were relatively low antibody responses, especially among HSV-seronegative individuals. The low ADCC responses may be associated with the poor efficacy of this vaccine observed in clinical trials.

Objective: To determine risk factors for early readmission to the hospital in patients with AIDS and pneumonia., Design: Case-control analysis., Setting: A municipal teaching hospital serving an indigent population., Patients: Case patients were all AIDS patients hospitalized with Pneumocystis carinii pneumonia or bacterial pneumonia between January 1992 and March 1995 who were readmitted for any nonelective reason within 2 weeks of discharge (n = 90). Control patients were randomly selected AIDS patients admitted during the study period who were not early readmissions (n = 87), matched by proportion of Pneumocystis carinii to bacterial pneumonia., Measurements and Main Results: Demographics, social support, health-related behaviors, clinical aspects of the acute hospitalization, and general medical status were the main predictors measured., Results: Patients were at significantly increased risk of early readmission if they left the hospital unaccompanied by family or friend (odds ratio [OR] 4.76; 95% confidence interval [CI] 2.06, 11.0; p =.0003), used crack cocaine (OR 3.40; 95% CI 1.02, 11.3; p =. 046), had one or more coincident AIDS diagnoses (OR 3.65; 95% CI 1. 44, 9.26; p =.0065), or had been admitted in the preceding 6 months (OR 2.82; 95% CI 1.21, 6.57; p =.016). Demographic characteristics, alcoholism, intravenous drug use, illness severity on admission, and length of hospitalization did not predict early readmission., Conclusions: Absence of companion at discharge and crack use were important risk factors for early readmission in patients with AIDS and pneumonia. Additional AIDS comorbidity and recent antecedent hospitalization were also risk factors; however, demographics and measures of acute illness during index hospitalization did not predict early readmission.

Our objective was to examine the efficacy and toxicity of continuous, low-dose interferon-alpha therapy for human immunodeficiency virus-related immune thrombocytopenic purpura (HIV-ITP) in a Phase II clinical trial overseen by a community-based consortium of physicians conducting clinical trials in HIV-related diseases. Sixteen patients with HIV-ITP defined by prospective clinical criteria were enrolled; the majority had failed other therapies for HIV-ITP. Baseline and serial measurements were made of platelet counts, complete blood counts, serum chemistries, platelet-associated immunoglobulin, and CD4+ T-lymphocyte counts; subjective symptoms and bleeding were recorded. Three million units of interferon-alpha 2b were self-administered by subcutaneous injection every Monday, Wednesday, and Friday for 16 weeks. Thirteen participants were evaluable for response. One obtained a complete response, eight had partial responses, and four had no response to interferon-alpha therapy. The mean absolute platelet count of the group rose from 15.5 x 10(9)/L at baseline to 47.3 x 10(9)/L at 2 weeks and remained in this range for the duration of the study. CD4+ T-lymphocyte counts and serum chemistries did not change significantly during therapy. Ability to detect platelet-associated immunoglobulin did not change in a predictable manner in relation to platelet count response. Hematologic toxicity was limited to one episode of granulocytopenia, which resolved after a lowering of zidovudine dosage. Subjective toxicities were mild and tolerable, and minor bleeding problems improved in all participants so affected. Low-dose, continuous therapy with interferon-alpha resulted in meaningful increases in the platelet counts of the majority of study participants with HIV-ITP. Interferon-alpha was safe and tolerable for most participants with HIV-ITP at the dosage and schedule employed in this study. Interferon-alpha for clinically significant thrombocytopenia and who have failed to respond to zidovudine.

Because vertical transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant occurs in only 15%-35% of possible opportunities, natural immune defenses of the mother, fetus, or neonate may be protective against infection. The relation between antibody-dependent cellular cytotoxicity (ADCC) antibodies and HIV-1 infection was explored in 78 neonates born to HIV-infected women. More than 90% of sera had measurable ADCC titers against HIV-1IIIB. Infant titers were closely correlated with maternal titers but were independent of total IgG and total antibody reactive to the same strain in whole virus ELISA. At birth, mean ADCC antibody levels of infants or their mothers were the same for infants who were infected and those who ultimately seroreverted and remained healthy. ADCC antibody titers against HIV-1SF2 were weakly correlated with anti-HIV-1IIIB titers and did not predict protection from HIV-1 infection. High levels of anti-HIV-1 ADCC antibody at birth are not protective against vertical transmission of HIV-1.

The epitopes on herpes simplex virus (HSV) glycoprotein B (gB) recognized by sera of 23 patients with well-characterized HSV infection were studied. Twelve epitope-specific monoclonal antibodies with neutralization (NT) or antibody-dependent cellular cytotoxicity (ADCC) activities were used in competitive ELISA binding inhibition studies. The sera were additionally analyzed for homologous viral type NT, ADCC activity, and gB-reactive antibody by ELISA. Seroconversion was observed in each assay during convalescence. Relative type specificity for sera from HSV-1-infected but not from HSV-2-infected individuals was demonstrated in the ADCC assay. Sera from HSV-infected patients contained antibodies recognizing 9 of 12 epitopes, representing 5 of the 6 characterized antigenic domains of gB tested. Two of the epitopes were blocked in a type-specific fashion. The incidence of epitopic recognition increased gradually with time and was delayed compared with the detection of functional ADCC or NT activity and overall antibody recognition of gB in the ELISA.