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D Rimland

Publications and source records attributed to D Rimland.

At least 19 recordsLinked to original sources

Prevention of cryptococcosis in HIV-infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis.

Despite advances in the treatment of HIV disease, the incidence and mortality of invasive cryptococcal disease remain significant. A matched, case-control study was performed to examine the impact of highly active antiretroviral therapy (HAART) and azole use on the incidence of invasive cryptococcal disease in HIV-infected patients. The study was performed at a metropolitan hospital with a large indigent population and an incidence of seven cases of cryptococcal disease per 1000 persons with AIDS. Bivariate analysis, matched on CD4 count, revealed that both HAART use [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.99] and azole use (OR 0.14; 95% CI 0.06-0.34) had a protective effect. Conditional logistic regression stratified on CD4 lymphocyte count revealed a protective role for azole use (OR 0.15; 95% CI 0.06-0.40) but not for HAART use (OR 0.47; 95% CI 0.18-1.26). Of note, the prevalence of HAART use was low in both cases and controls, with only 12% of cases and 23% of controls on HAART. The results of this study support previous evidence that azole use prevents invasive cryptococcal disease. Although current guidelines for the prophylaxis of opportunistic infections do not suggest routine prophylaxis for cryptococcal infection, this issue should be reconsidered, especially in populations that have a low prevalence of HAART use.

AIDS-Related Opportunistic Infections↗

Antiretroviral therapy in HIV-positive men is associated with increased apolipoprotein CIII in triglyceride-rich lipoproteins.

OBJECTIVES: Dyslipidaemia has become a common problem in HIV disease, especially in patients on current antiretroviral therapy. However, the pathogenic mechanisms involved are not well understood or documented using conventional lipid measurements. METHODS: Using a cross-sectional design, the prevalence of abnormal standard lipid measurements and novel biomarkers for abnormal lipid metabolism was determined in 271 HIV-positive men from two HIV clinics in Atlanta, GA, USA. RESULTS: A total of 147 men were treated with protease inhibitors (PIs) for >3 months (54%), 84 were treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) for >3 months (31%) and 40 had not received antiretroviral therapy in the past 3 months (15%). Patients being treated with a PI had higher total cholesterol and triglyceride (TG) levels than patients on no therapy (P<0.05 for each). Patients in the NNRTI group had higher TG, lower high-density lipoprotein (HDL) levels, and higher low-density lipoprotein (LDL) levels than patients on no therapy (P<0.05 for each). Patients treated with either PIs or NNRTIs were more likely to have higher apolipoprotein CIII (apoCIII) levels (P<0.05 for each) than patients on no therapy. Elevated TG was associated with disproportionably elevated apoCIII levels in both treatment groups. CONCLUSIONS: In this cross-sectional study of HIV-infected men, either PI or NNRTI therapy elevated levels of TG and apoCIII. Higher concentrations of apoCIII in apoB-containing lipoproteins [very low-density lipoproteins (VLDLs), intermediate density lipoprotein (IDL) and LDLs] have been predictive of an increased incidence of coronary events in clinical trials and more rapid progression of coronary lesions measured by angiography. These findings, on a background of an older population with additional risk factors of smoking and diabetes, portend future atherosclerotic events in these patients.

Adult↗

Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection.

OBJECTIVES: To study prospectively HIV-positive patients admitted to the hospital because of pneumonia by extensive laboratory tests to determine specific microbiologic diagnoses and to establish the best clinical diagnosis after review of all available data by expert clinicians. METHODS: Patients admitted to one of two hospitals had extensive questionnaires completed and defined diagnostic tests performed on blood, sputum, urine and bronchoalveolar lavage specimens, when available. RESULTS: A total of 230 patients had a diagnosis of pneumonia verified. A definite or probable etiologic diagnosis was made in 155 (67%) of these patients. Pneumocystis carinii caused 35% of all cases of pneumonia. Twenty-seven percent of cases of pneumonia with a single etiology had a definite or probable bacterial etiology. 'Atypical agents' were distinctly uncommon. Few clinical or laboratory parameters could differentiate specific etiologies. CONCLUSIONS: P. carinii continues to be a common cause of pneumonia in these patients. The rarity of 'atypical agents' could simplify the empiric approach to therapy. Despite the use of extensive testing we did not find a definite etiology in a large number of cases.

AIDS-Related Opportunistic Infections↗

Infections with Ehrlichia chaffeensis and Ehrlichia ewingii in persons coinfected with human immunodeficiency virus.

The clinical course and laboratory evaluation of 21 patients coinfected with human immunodeficiency virus (HIV) and Ehrlichia chaffeensis or Ehrlichia ewingii are reviewed and summarized, including 13 cases of ehrlichiosis caused by E. chaffeensis, 4 caused by E. ewingii, and 4 caused by either E. chaffeensis or E. ewingii. Twenty patients were male, and the median CD4(+) T lymphocyte count was 137 cells/microL. Exposures to infecting ticks were linked to recreational pursuits, occupations, and peridomestic activities. For 8 patients, a diagnosis of ehrlichiosis was not considered until > or =4 days after presentation. Severe manifestations occurred more frequently among patients infected with E. chaffeensis than they did among patients infected with E. ewingii, and all 6 deaths were caused by E. chaffeensis. Ehrlichiosis may be a life-threatening illness in HIV-infected persons, and the influence of multiple factors, including recent changes in the epidemiology and medical management of HIV infection, may increase the frequency with which ehrlichioses occur in this patient cohort.

Adult↗

Intracellular cytokines in the acute response to highly active antiretroviral therapy.

OBJECTIVES: Successful highly active antiretroviral therapy (HAART) is usually associated with a rapid decline in HIV plasma RNA levels and a gradual increase in CD4 T cells. We examined whether changes in cytokine production and profile precede other immunological changes and whether these might occur in temporal association with plasma HIV RNA changes. DESIGN AND METHODS: Eleven HIV-1-infected patients were enrolled into a prospective cohort study; eight patients were naive to antiretroviral therapy. Blood samples were collected pre-therapy (week 0) and at 1, 2, and 3 weeks post-initiation of therapy. RESULTS: All 11 patients enrolled remained on triple HAART for 1 week, eight for 2 weeks, and six for > or = 3 weeks. When compared to week 0, these patients had a > or = 2-log10 decline in HIV plasma RNA levels and/or a decline to < or = 400 copies/ml by week 3 of therapy (p = 0.004). The numbers and percentages of CD4 and CD8 T cells, and the percentage of naive, memory, and activated T cells did not change significantly between weeks 0 and 1 or 0 and 3. Of all the immune parameters examined only: the percentage of CD4 T cells spontaneously producing tumor necrosis factor (TNF)-alpha (median, 2.4 versus 0.5% P = 0.025); the percentage of CD8 T cells spontaneously producing TNF-alpha (median, 0.6 versus 0.2% P = 0.037); and the percentage of CD3 T cells spontaneously producing interleukin-4 (median, 1.8 versus 0.8% P = 0.004) changed significantly between weeks 0 and 3. CONCLUSIONS: In these patients, decreases in the percentage of T cells spontaneously producing TNF-alpha or interleukin-4 preceded changes in CD4 T cells. If confirmed by others, these observations may be useful as early predictors of response to and early failure of HAART.

Adult↗

Effect of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of P carinii pneumonia in patients with HIV-1: a prospective study.

BACKGROUND: Investigators have reported that patients infected with Pneumocystis carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a worse outcome than those infected with P carinii containing wild-type DHPS. We investigated patients with HIV-1 infection and P carinii pneumonia to determine if DHPS mutations were associated with poor outcomes in these patients. METHODS: We compared presence of mutations at the DHPS locus with survival and response of patients to co-trimoxazole or other drugs. FINDINGS: For patients initially given co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%) of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of 66 patients with a DHPS mutant did not respond to treatment, compared with 13 (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16 with the wild type died (0.25 [0.09-0.67]; p=0.005). INTERPRETATION: These results, by contrast with those of previous studies, suggest that patients with wild-type P carinii do not have a better outcome than patients with the mutant when given co-trimoxazole. Our results suggest that presence of a DHPS mutation should be only one of several criteria guiding the choice of initial drug treatment of P carinii pneumonia in patients with HIV-1 infection.

AIDS-Related Opportunistic Infections↗

Serotonin syndrome in HIV-infected individuals receiving antiretroviral therapy and fluoxetine.

OBJECTIVE: To describe HIV-infected individuals taking antidepressants who developed the serotonin syndrome due to drug--drug or drug--food interactions. DESIGN AND SETTING: Case studies carried out at the HIV Outpatient Clinic, Atlanta Veterans Affairs Medical Center. PARTICIPANTS AND INTERVENTIONS: HIV-positive patients who were receiving antiretroviral and antidepressant therapies and presented with symptoms consistent with the serotonin syndrome. Their antidepressants were discontinued or the doses reduced in order to resolve the symptoms. RESULTS: Five cases of serotonin syndrome developed after patients who were taking antidepressants ingested P450 inhibitors. CONCLUSIONS: Serotonin syndrome should be suspected in patients on serotonergic medications who present with mental status change, autonomic dysfunction, and neuromuscular abnormalities. Suspicion should be heightened in those who are ingesting substances known to inhibit P450 enzymes, such as protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and grapefruit juice.

Adult↗

CCR5 and CXCR4 expression on memory and naive T cells in HIV-1 infection and response to highly active antiretroviral therapy.

OBJECTIVE: To measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets, measures of disease activity, and response to highly active antiretroviral therapy (HAART). DESIGN: Fourteen untreated HIV-1-infected patients, 18 patients at 3-to 4-weeks after beginning HAART, and 35 uninfected control subjects were studied. METHODS: Four-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure their expression of CCR5, CXCR4, and CD38. RESULTS: HIV-1-infected patients had higher CCR5 levels and lower CXCR4 levels on CD4 and CD8 T cells and their CD45RO/CD45RA subsets than control subjects did. However, CCR5 elevation was statistically significant only for CD4 T cells and their subsets, and CXCR4 depression was significant for CD8 T cells and their subsets (and for CD4:CD45RO cells). The elevation of CCR5 and depression of CXCR4 were not due to shifts in CD45RO/CD45RA subset proportions but to upregulation or downregulation within the subsets. CCR5 elevation on CD4 T cells was significantly restored toward normal by HAART, but the CXCR4 depression was not. CCR5 expression but not CXCR4 expression correlated with other measures of immunodeficiency (CD4 T-cell levels), active infection (viral load), and cellular activation (CD38). CONCLUSIONS: CCR5 elevation is a concomitant of immune activation and viral replication that occurs in HIV-1 infection, but the relation of CXCR4 depression to severity of infection, disease progression, and response to therapy remains undefined.

Adult↗

Molecular epidemiology of Candida albicans strains isolated from the oropharynx of HIV-positive patients at successive clinic visits.

Candida albicans strain diversity and fluconazole resistance were prospectively analyzed in oral strains from 29 adult human immunodeficiency virus (HIV)-positive patients followed for > 1 year who had five or more culture-positive clinic visits. Molecular typing consisted of genomic blots probed with the Ca3 repetitive element. Sixteen patients had one or more episodes of oropharyngeal candidiasis (OPC), 12 (75%) maintained the original genotype, whereas the remaining four patients had a succession of 2-3 genotypes. The original genotype, either alone or mixed with another strain or with non-C. albicans Candida spp., was recovered from oral lesions in 13 of 15 evaluable (86.7%) patients. C. dubliniensis was the infecting yeast in the remaining two patients. Different patterns of fluconazole resistance occurred in three OPC patients. One patient's infecting strain became less susceptible. A second patient was infected with a resistant genotype and a progressively more susceptible minor genotype variant. C. dubliniensis isolates from the third patient varied in susceptibility. Thirteen colonized patients who never developed OPC harbored a greater variety of C. albicans genotypes (2-6) than their infected counterparts (P = 0.35). OPC patients maintained their original endogenous C. albicans strains for prolonged periods, whether or not they demonstrated decreased in vitro susceptibility to fluconazole. The adaptation and maintenance of an endogenous C. albicans strain within its host may be linked to as yet uncharacterized factors.

AIDS-Related Opportunistic Infections↗

Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates in the United States: 1992 to 1994 and 1996 to 1998.

The antifungal drug susceptibilities of two collections of Cryptococcus neoformans isolates obtained through active laboratory-based surveillance from 1992 to 1994 (368 isolates) and 1996 to 1998 (364 isolates) were determined. The MICs of fluconazole, itraconazole, and flucytosine were determined by the National Committee for Clinical Laboratory Standards broth microdilution method; amphotericin B MICs were determined by the E-test. Our results showed that the MIC ranges, the MICs at which 50% of isolates are inhibited (MIC(50)s), and the MIC(90)s of these four antifungal agents did not change from 1992 to 1998. In addition, very small numbers of isolates showed elevated MICs suggestive of in vitro resistance. The MICs of amphotericin B were elevated (>or=2 microg/ml) for 2 isolates, and the MICs of flucytosine were elevated (>or=32 microg/ml) for 14 isolates. Among the azoles, the fluconazole MIC was elevated (>or=64 microg/ml) for 8 isolates and the itraconazole MIC (>or=1 microg/ml) was elevated for 45 isolates. Analysis of 172 serial isolates from 71 patients showed little change in the fluconazole MIC over time. For isolates from 58 patients (82% of serial cases) there was either no change or a twofold change in the fluconazole MIC. In contrast, for isolates from seven patients (12% of serial cases) the increase in the MIC was at least fourfold. For isolates from another patient there was a 32-fold decrease in the fluconazole MIC over a 1-month period. We conclude that in vitro resistance to antifungal agents remains uncommon in C. neoformans and has not significantly changed with time during the past decade.

Antifungal Agents↗

Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients.

BACKGROUND: We conducted a retrospective case-control study to evaluate effectiveness of pneumococcal vaccine against invasive disease among adults with human immunodeficiency virus (HIV) infection in San Francisco, Calif, and Atlanta, Ga. METHODS: Case patients were 18- to 55-year-old subjects with HIV infection who were admitted to selected hospitals in Atlanta or San Francisco from February 1992 to April 1995 from whom Streptococcus pneumoniae was isolated from a normally sterile site. Controls were HIV-infected patients of similar age matched to cases by hospital of admission and CD4 lymphocyte count (<0.20, 0.20-0.499, >/=0.50 x 10(9)/L [<200, 200-499, >/=500 cells/mm(3)]) or clinical stage of acquired immunodeficiency syndrome. Case and control subjects were restricted to persons known to have HIV infection before hospital admission. Analysis used matched univariate and conditional logistic regression. RESULTS: One hundred seventy-six case patients and 327 controls were enrolled. By univariate analysis, persons with pneumococcal disease were more likely to be black, be current smokers, and have close contact with children. Adjusted for these factors and CD4 cell count, pneumococcal vaccine effectiveness was 49% (95% confidence interval [CI], 12%-70%). Adjusting for all variables and key interaction terms, vaccine effectiveness among whites was 76% (95% CI, 35%-91%), whereas effectiveness among blacks was 24% (95% CI, -50% to 61%). Among controls, vaccination was significantly less common among blacks (29% vs 45%; P<.005). CONCLUSIONS: Pneumococcal vaccine demonstrated protection against invasive pneumococcal infections among white but not black HIV-infected adults. Failure to demonstrate effectiveness among blacks may be due to limited power because of low use of the vaccine in this population, immunization at more advanced stages of immunosuppression, or unmeasured factors. These data support current recommendations for use of pneumococcal vaccine in HIV-infected persons and highlight a clear need for strategies to improve vaccine-induced protection.

AIDS-Related Opportunistic Infections↗

Sulfa or sulfone prophylaxis and geographic region predict mutations in the Pneumocystis carinii dihydropteroate synthase gene.

To determine factors associated with mutations in the Pneumocystis carinii dihydropteroate synthase (DHPS) gene, a prospective study of human immunodeficiency virus (HIV)-infected patients with confirmed P. carinii pneumonia was conducted in Atlanta, Seattle, and San Francisco. Clinical information was obtained from patient interview and chart abstraction. DHPS genotype was determined from DNA sequencing. Overall, 76 (68.5%) of 111 patients had a mutant DHPS genotype, including 22 (81.5%) of 27 patients from San Francisco. In multivariate analysis, sulfa or sulfone prophylaxis and study site were independent predictors of a mutant genotype. Fourteen (53.8%) of 26 patients who were newly diagnosed with HIV infection and had never taken prophylaxis had a mutant genotype. The significance of geographic location as a risk factor for mutant genotype and the high proportion of mutant genotypes among persons never prescribed prophylaxis, including those newly diagnosed with HIV infection, provide indirect evidence that these mutations are transmitted from person to person either directly or through a common environmental source.

AIDS-Related Opportunistic Infections↗

Effect of clinical events on plasma HIV-1 RNA levels in persons with CD4+ T-lymphocyte counts of more than 500 x 10(6) cells/l.

OBJECTIVE: Immune stimulation of CD4 lymphocytes is thought to enhance HIV-1 replication in vivo. Therefore, we sought to define the impact of clinical events identified as putative immune activators on the variability of plasma HIV-1 RNA levels in persons with CD4 cell counts greater than 500 x 10(6) cells/l. DESIGN: We prospectively recorded clinical events and measured plasma HIV-1 RNA levels weekly for 24 weeks in 16 HIV-1-infected adults who were not receiving antiretroviral therapy and who had CD4 cell counts greater than 500 x 10(6) cells/l. METHODS: Standard weekly interviews were conducted to capture potential immune activators (e.g., infections, immunizations, and allergic reactions). All plasma HIV-1 RNA levels were measured using the Amplicor HIV-1 Monitor assay (Roche Diagnostics, Branchburg, New Jersey, USA) according to the manufacturer's instructions. RESULTS: Participants had remarkably stable viral loads during the 6 month study period. Infections were significantly more frequent during the 7 days prior to individual HIV-1 RNA measurements that exceeded the assay variation thresholds determined for this study (+/- 0.324 log) than during the comparable time periods preceding stable measurements (P = 0.023). As a group, the eight participants who had one to four HIV-1 RNA measurements that exceeded the thresholds experienced more infections and declining CD4 cell counts over the study course compared to the eight participants whose measurements all fell within the thresholds (P = 0.058 and 0.053 respectively). CONCLUSIONS: Our study suggests that in untreated HIV-1-infected persons with CD4 cell count greater than 500 x 10(6) cells/l, viral load is generally quite stable, although acute minor infections are associated with transient fluctuations generally lasting no more than 1 week.

Acquired Immunodeficiency Syndrome↗

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Journal Article↗

Risk factors for community-acquired pneumonia among persons infected with human immunodeficiency virus.

Two hundred eleven adults with human immunodeficiency virus (HIV) infection hospitalized for community-acquired pneumonia, including Pneumocystis carinii pneumonia (PCP; patients), and 192 matched HIV-infected hospitalized patients without pneumonia (controls) were interviewed to determine risk factors for pneumonia. Multivariate logistic regression showed that patients were less likely than controls to have used trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.12-0.41) and more likely to have been hospitalized previously with pneumonia (OR, 6.25; CI, 3.40-11.5). Patients were also more likely than controls to have gardened (OR, 2.24; CI, 1.00-5.02) and to have camped or hiked (OR, 4.95; CI, 1.31-18.7), but stratified analysis by etiologic agent showed this association only for PCP. These findings reconfirm the efficacy of TMP-SMZ in preventing community-acquired pneumonia. In addition, hospitalization for pneumonia might represent a missed opportunity to encourage HIV-infected patients to enter into regular medical care and to adhere to prescribed antiretroviral and prophylaxis medications.

Adult↗

Declining CD4+ T-lymphocyte counts are associated with increased risk of enteric parasitosis and chronic diarrhea: results of a 3-year longitudinal study.

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

AIDS-Related Opportunistic Infections↗

APIC position paper: immunization. Association for Professionals in Infection and Epidemiology, Inc.

The Association for Professionals in Infection Control and Epidemiology, Inc. (APIC) is a multidisciplinary organization of more than 11,000 health care professionals who practice infection control and epidemiology within a variety of health care settings. As an authority in infection control, APIC endorses the Advisory Committee on Immunization Practices (ACIP) recommendations that are published by the Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. APIC supports the immunization initiative of the Healthy People 2000: National Health Promotion and Disease Prevention Objectives, which contains a national strategy for significantly improving the health of the nation, including preventing infectious diseases through immunization.

Adult↗