Acquired Immunodeficiency Syndrome: Collier AC

Murphy EL, Collier AC, Kalish LA, Assmann SF, Para MF, Flanigan TP, Kumar PN, Mintz L, Wallach FR, Nemo GJ, Anonymous00313. · Department of Laboratory Medicine, University of California, San Francisco, Box 0884, San Francisco, CA 94143-0884, USA. · Ann Intern Med. · Pubmed #11434728 links to  free full text

Abstract: BACKGROUND: Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active anti-retroviral therapy (HAART), but previous studies may have been confounded by other changes in treatment. OBJECTIVE: To assess the benefit of HAART in patients with advanced AIDS and anemia. DESIGN: Prospective, multicenter cohort study. SETTING: The Viral Activation Transfusion Study (VATS), with enrollment from August 1995 through July 1998 and follow-up through June 1999. PATIENTS: 528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia. MEASUREMENTS: In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use. RESULTS: At baseline, patients had a median CD4(+) lymphocyte count of 0.015 x 10(9) cell/L, median plasma HIV RNA level of 4.8 log(10) copies/mL, and median hemoglobin concentration of 73 g/L. Use of HAART increased from 1% of active patients in January 1996 to 79% of active patients in January 1999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.001 for both comparisons). Rates of non-CMV disease were 0.15 event/ person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 [ P < 0.001]; adjusted rate ratio, 0.66 [ P < 0.05]). Rates of CMV disease were 0.10 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 [ P < 0.01]; adjusted rate ratio, 1.01 [ P > 0.2]). Results were similar in patients with baseline CD4(+) lymphocyte counts less than 0.010 x 10(9) cells/L. CONCLUSIONS: The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART.

Berrey MM, Schacker T, Collier AC, Shea T, Brodie SJ, Mayers D, Coombs R, Krieger J, Chun TW, Fauci A, Self SG, Corey L. · Department of Medicine, University of Washington, Seattle, WA, USA. · J Infect Dis. · Pubmed #11319682 No free full text.

Abstract: Immunologic data supporting immediate antiretroviral therapy in primary human immunodeficiency virus type 1 (HIV-1) infection are emerging; however, clinical benefit has not been demonstrated. The clinical and virologic course of 47 patients who were enrolled from September 1993 through June 1996 and who were not initially treated with potent therapy was compared with the course of 20 patients who immediately began therapy with zidovudine, lamivudine, and indinavir. Demographic and baseline laboratory data were comparable. During 78 weeks of follow-up, the early-treatment cohort showed a reduced frequency of opportunistic infections (5% vs. 21.3%; relative risk, 0.11; P=.02), less frequent progression to AIDS (13% vs. 0%), and significantly less frequent nonopportunistic mucocutaneous disorders and respiratory infections (P<.01). Plasma HIV-1 RNA levels were <50 copies/mL in all patients who continued therapy; however, after 9--12 months, HIV-1 remained detectable in latently infected CD4(+) T cells and in lymph node mononuclear cells. Combination antiretroviral therapy during primary HIV-1 infection demonstrated a decreased frequency of minor opportunistic infections, mucocutaneous disorders, and respiratory infections and reduced progression to AIDS.

Collier AC, Kalish LA, Busch MP, Gernsheimer T, Assmann SF, Lane TA, Asmuth DM, Lederman MM, Murphy EL, Kumar P, Kelley M, Flanigan TP, McMahon DK, Sacks HS, Kennedy MS, Holland PV, Anonymous00197. · School of Medicine, University of Washington, Seattle, WA 98104, USA. · JAMA. · Pubmed #11268267 links to  free full text

Abstract: CONTEXT: Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs). OBJECTIVE: To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients. DESIGN AND SETTING: Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors). PATIENTS: A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion). MAIN OUTCOME MEASURES: Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion. RESULTS: At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels. CONCLUSIONS: We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.

Ellis RJ, Marquie-Beck J, Delaney P, Alexander T, Clifford DB, McArthur JC, Simpson DM, Ake C, Collier AC, Gelman BB, McCutchan JA, Morgello S, Grant I, Anonymous00105. · University of California, San Diego, San Diego, CA, USA. · Ann Neurol. · Pubmed #19067367 No free full text.

Abstract: OBJECTIVE: Two recent analyses found that exposure to protease inhibitors (PIs) in the context of antiretroviral (ARV) therapy increased the risk for distal sensory polyneuropathy (DSPN) in subjects with human immunodeficiency virus (HIV) infection. These findings were supported by an in vitro model in which PI exposure produced neurite retraction and process loss in dorsal root ganglion sensory neurons. Confirmation of peripheral nerve toxicity with PIs could substantially limit their long-term use in highly active ARV therapy. METHODS: We evaluated current and past exposure to PIs as a risk factor for DSPN in 1,159 HIV-infected individuals enrolled in a large, prospective, observational, multicenter study. Signs of DSPN were ascertained by neurological examination. Subjects were grouped into categories according to past and current exposure to any ARV and to PIs. We included disease indicators such as nadir CD4, plasma viral load, and duration of HIV infection, as well as advancing age and exposure to dideoxynucleoside ARVs in multivariate models. RESULTS: In univariate analyses, both past and current PI exposure significantly increased the risk for DSPN. However, after adjusting for previously validated concomitant risk factors in multivariate models, none of the PI exposure groups was more likely to have DSPN than ARV naive subjects. A secondary evaluation of duration of PI use and exposure to individual PI drugs was similarly nonsignificant in multivariate models, except for small effects of amprenavir and lopinavir. INTERPRETATION: Evaluation of concomitant risks for HIV DSPN suggests that the independent risk attributable to PIs, if any, is small. This risk must be weighed against the important role of PIs in modern ARV therapy regimens.

Letendre SL, Marquie-Beck J, Ellis RJ, Woods SP, Best B, Clifford DB, Collier AC, Gelman BB, Marra C, McArthur JC, McCutchan JA, Morgello S, Simpson D, Alexander TJ, Durelle J, Heaton R, Grant I, Anonymous00101. · University of California, 150 W. Washington St., San Diego, CA 92103, USA. · J Neuroimmune Pharmacol. · Pubmed #18040835 No free full text.

Abstract: BACKGROUND: Effective antiretroviral therapy (ART) has reduced the incidence of HIV-associated neurocognitive impairment (HNCI) but its prevalence remains high. Clinical trials have yet to identify a consistently effective treatment for HNCI, other than ART, but in vitro data support that some drugs approved by the Food and Drug Administration (FDA) for other indications might benefit individuals with HNCI. Some of these drugs, such as serotonin reuptake inhibitors (SRIs) and HMG-CoA reductase inhibitors (statins), may do so by reducing HIV replication in the CNS and are already widely used by HIV-infected individuals. METHODS: Six-hundred fifty-eight HIV-infected participants of the CHARTER cohort had a baseline assessment, which included comprehensive neuropsychological (NP) testing and HIV RNA measurements in plasma and cerebrospinal fluid (CSF). Four-hundred sixty-seven (71%) subjects used ART, 195 (30%) used SRIs, and 63 (10%) used statins. RESULTS: SRI users were less likely to have HIV RNA levels in CSF above 50 copies (c)/mL (29 vs. 37% in non-SRI users, OR 0.69, p = 0.05). This association was most evident for three of the seven SRIs (citalopram, sertraline, and trazodone, or "antiviral" SRIs, combined 25 vs. 38% in non-SRI users, OR 0.56, p = 0.01) and was strongest in those not taking concomitant ART (61 vs. 83%, OR 0.31, p = 0.01). "Antiviral" SRI users also performed better on NP tests (median global deficit score 0.37 vs. 0.47, p = 0.04). Statin users were also less likely to have HIV RNA levels in CSF above 50 c/mL (16 vs. 37%, p < 0.001) but, in contrast to SRIs, the association was strongest in those taking ART (2 vs. 18%, p < 0.001). Statin use was not associated with better NP performance. Multivariate analyses indicated that the use of "antiviral" SRIs-but not statins-was associated with undetectable HIV RNA levels in CSF and better NP performance. CONCLUSIONS: SRIs may reduce HIV replication in CSF and improve NP performance. This was particularly true for three SRIs-supporting differences in antiviral efficacy between drugs-in individuals who were not taking ART. In contrast, statins were not associated with lower HIV replication in CSF in multivariate analyses and were not associated with better NP performance. These analyses support the value of large observational cohort studies in identifying FDA-approved drugs that may be worth further investigation.

Curtis JR, Patrick DL, Caldwell ES, Collier AC. · Department of Medicine, University of Washington, Seattle 98104-2499, USA. · Arch Intern Med. · Pubmed #10847263 links to  free full text

Abstract: BACKGROUND: Patients with chronic and terminal disease frequently do not talk to their physicians about end-of-life care. Interventions to improve this communication have generally been unsuccessful, suggesting that important barriers to this communication must exist. OBJECTIVES: To determine the barriers to and facilitators of patient-clinician communication about end-of-life care and to identify barriers and facilitators that are more common among those patients who are least likely to discuss end-of-life care: minorities and injection drug users. METHODS: We conducted a prospective study of 57 patients with advanced acquired immunodeficiency syndrome and their primary care clinicians who were recruited from university and private clinics. Barriers to and facilitators of end-of-life communication were identified from a prior qualitative study and assessed for frequency and importance and for an association with the occurrence and quality of end-of-life communication. RESULTS: Clinicians identified more barriers than patients. Barriers identified by patients and clinicians fell into 3 categories of potential interventions: education about end-of-life care, counseling to help address end-of-life concerns, and health care system changes to facilitate patient-clinician communication. Although none of the patient-identified barriers was associated with the occurrence of communication, 2 clinician-identified barriers were associated with less communication: "the patient has not been very sick yet" and "the patient isn't ready to talk about end-of-life care." Nonwhite patients were more likely to identify the following 2 barriers than white patients: "I feel that if I talk about death, it could bring death closer" and "I don't like to talk about the care I want if I get very sick." CONCLUSIONS: The diversity of barriers and facilitators relevant to patients with acquired immunodeficiency syndrome and their clinicians suggests that interventions to improve communication about end-of-life care must be focused on individual needs and must involve counseling interventions and health system changes in addition to education. Clinician barriers are more common and more strongly associated with the occurrence of end-of-life communication than patient barriers, suggesting that clinicians are an important target group for improving this communication.

Curtis JR, Patrick DL, Caldwell ES, Collier AC. · Department of Medicine, University of Washington, Seattle, USA. · Arch Intern Med. · Pubmed #10847252 links to  free full text

Abstract: BACKGROUND: The medical futility rationale asserts that physicians need not offer their patients therapies that have zero or close to zero probability of success. The rationale is controversial, but it is used in practice. OBJECTIVE: To examine the attitudes of patients with advanced acquired immunodeficiency syndrome (AIDS) toward the medical futility rationale as it might apply to their medical care. METHODS: We conducted a cross-sectional study with interviewer-administered questionnaires. Fifty-seven patients with advanced AIDS (C3 stage AIDS and a CD4 cell count <100/microL) were recruited from academic and private clinics. MAIN OUTCOME MEASURE: Whether patients believe it is acceptable for physicians to withhold mechanical ventilation, without offering it, if physicians determine the intervention is futile. RESULTS: Sixty-one percent of patients (n=35) believed that it was definitely acceptable for their physician to not offer mechanical ventilation if the physician judged this intervention to be futile, and 26% (n= 15) believed this was probably acceptable. Less than 10% of patients (n= 5) said not offering therapy judged futile was definitely not acceptable. Patients who were less likely to prefer mechanical ventilation in different hypothetical health states were significantly more likely to accept decisions on the basis of futility (P=.003). Health-related quality of life, patient satisfaction with medical care, and patient-clinician communication about end-of-life care were not associated with attitudes toward medical futility. CONCLUSIONS: Although the majority of patients with advanced AIDS accept the medical futility rationale, a substantial minority do not. Acceptance of this rationale was associated with wanting less life-sustaining treatment. Physicians invoking the medical futility rationale and hospitals using policies incorporating the medical futility rationale should take into account this diversity in the attitudes toward medical futility.

Curtis JR, Patrick DL, Caldwell E, Greenlee H, Collier AC. · Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, USA. · AIDS. · Pubmed #10397544 No free full text.

Abstract: OBJECTIVE: To assess prevalence and quality of end-of-life communication between persons with advanced AIDS and their clinicians and to identify patient and clinician characteristics associated with this communication. DESIGN: Prospective cohort study of 57 patients with AIDS and their primary care clinicians. SETTING: University-based and private clinics in Seattle, Washington. PATIENTS: Patients had a prior AIDS-defining illness and a CD4 cell count of less than 100 x 10(6) cells/l. MAIN OUTCOME MEASURES: Quality of patient-clinician communication about end-of-life care, validated against patient satisfaction and patient-clinician concordance on advance directives and treatment preferences. RESULTS: Patients reported they had communication about end-of-life care with their clinician in 31 of 57 cases (54%) while clinicians reported they had this discussion in 36 of 57 cases (64%). Patients and clinicians gave concordant answers in 42 patient-clinician pairs. In 15 pairs (26%), patients and clinicians disagreed about whether end-of-life communication had occurred. African-American and Hispanic patients were less likely to report having communication than non-Hispanic white patients (chi-square analysis: chi2 = 4.67; P < 0.05); injection drug users and women with high-risk sexual partners were less likely to report communication than homosexual or bisexual men (chi2 = 4.67; P < 0.05). A four-item measure of patients' assessment of the quality of communication about end-of-life care had good internal consistency (Cronbach's alpha 0.81) and was significantly correlated with overall satisfaction with medical care (r2 = 0.76; P < 0.0001). Patients with lower income reported lower quality of communication (chi2 = 5.82; P = 0.05). If patients assessed quality of communication as high, their clinicians were more likely to know if the patient had a durable power of attorney for health care (chi2 = 4.95; P = 0.03) but were not more likely to predict patients' preferences for life-sustaining treatments. CONCLUSIONS: Quality of patient-clinician communication about end-of-life care can be measured in a brief questionnaire; higher quality of this communication is associated with higher satisfaction with care and increased clinician knowledge of patients' advance directives. Since socioeconomic status and ethnicity are associated with both the occurrence and quality of this communication, future interventions in end-of-life care should assess the effect of these variables. Given the important and independent goals of improving patient-clinician communication about end-of-life care and improving the quality of care at the end of life, future studies should test interventions to improve the quality of communication and determine whether improving this communication improves the quality of care at the end of life.