Search

Introduction: Patient preferences for long-acting antiretroviral therapies (LA-ART) should inform development of regimens with optimal adherence and acceptability. We describe a systematic process used to identify attributes and levels for a discrete choice experiment (DCE) designed to elicit preferences for potential LA-ART options in the US., Methods: Our approach was conducted in four stages: data collection, data reduction, removing inappropriate attributes, and optimizing wording. We started with 8 attributes defining potential LA-ART products based on existing literature and knowledge of products in development. We conducted 12 key informant interviews with experts in HIV treatment. The list of attributes, the set of plausible levels for each attribute, and restrictions on combinations of attribute levels were updated iteratively., Results: Despite uncertainty about which products will become available, key informant discussions converged on 4 delivery modes (infusions and patches were not considered immediately feasible) and 6 additional attributes. Treatment effectiveness and frequency of clinical monitoring were dropped. Oral lead-in therapy was split into two attributes: pre-treatment time undetectable and pre-treatment negative reaction testing. We omitted product-specific systemic and local side effects. In addition to mode, the final set of attributes included: frequency of dosing; location of treatment; pain; pre-treatment time undetectable; pre-treatment negative reaction testing; and late-dose leeway., Conclusions: A systematic process successfully captured elements that are both feasible and relevant to evaluating the acceptability of potential LA-ART alternatives to patients., (© 2022. The Author(s).)

In an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001-2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials: hazard ratio (HR) = 2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR = 1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR = 5.1 (95% CI: 1.6, 8.7); transported: HR = 5.4 (95% CI: -0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

During antiretroviral therapy (ART) that suppresses HIV replication to below the limit-of-quantification, virions produced during ART can be detected at low frequencies in the plasma, termed residual viremia (RV). We hypothesized that a reservoir of HIV-infected cells actively produce and release virions during ART that are potentially infectious, and that following ART-interruption, these virions can complete full-cycles of replication and contribute to rebound viremia. Therefore, we studied the dynamics of RV sequence variants in 3 participants who initiated ART after ~3 years of infection and were ART-suppressed for >6 years prior to self-initiated ART-interruptions. Longitudinal RV C2V5env sequences were compared to sequences from pre-ART plasma, supernatants of quantitative viral outgrowth assays (QVOA) of cells collected during ART, post-ART-interruption plasma, and ART-re-suppression plasma. Identical, "putatively clonal," RV sequences comprised 8-84% of sequences from each timepoint. The majority of RV sequences were genetically similar to those from plasma collected just prior to ART-initiation, but as the duration of ART-suppression increased, an increasing proportion of RV variants were similar to sequences from earlier in infection. Identical sequences were detected in RV over a median of 3 years (range: 0.3-8.2) of ART-suppression. RV sequences were identical to pre-ART plasma viruses (5%), infectious viruses induced in QVOA (4%) and rebound viruses (5%) (total n = 21/154 (14%) across the 3 participants). RV sequences identical to ART-interruption "rebound" sequences were detected 0.1-7.4 years prior to ART-interruption. RV variant prevalence and persistence were not associated with detection of the variant among rebound sequences. Shortly after ART-re-suppression, variants that had been replicating during ART-interruptions were detected as RV (n = 5). These studies show a dynamic, virion-producing HIV reservoir that contributes to rekindling infection upon ART-interruption. The persistence of identical RV variants over years suggests that a subpopulation of HIV-infected clones frequently or continuously produce virions that may resist immune clearance; this suggests that cure strategies should target this active as well as latent reservoirs., Competing Interests: The authors have declared that no competing interests exist.

Background: Women are underrepresented in human immunodeficiency virus (HIV) research in the United States. To determine if women screening for HIV clinical trials enrolled at lower rates than men, we performed a retrospective, cross-trial analysis., Methods: We conducted an analysis of screening and enrollment during 2003-2013 to 31 clinical trials at 99 AIDS Clinical Trials Group network research sites in the United States. Random-effects meta regression estimated whether sex differences in not enrolling ("screen out") varied by various individual, trial, or site characteristics., Results: Of 10 744 persons screened, 18.9% were women. The percentages of women and men who screened out were 27.9% and 26.5%, respectively (P = .19); this small difference did not significantly vary by race, ethnicity, or age group. Most common reasons for screening out were not meeting eligibility criteria (30-35%) and opting out (23%), and these did not differ by sex. Trial and research site characteristics associated with variable screen-out by sex included HIV research domain and type of hemoglobin eligibility criterion, but individual associations did not persist after adjustment for multiple testing., Conclusions: In the absence of evidence of significantly higher trial screen-out for women, approaching more women to screen may increase female representation in HIV trials., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

To better understand acceptability of long-acting injectable antiretroviral treatment (LAI-ART) regimens for HIV management, we conducted seven semi-structured focus group discussions with experienced HIV care providers and persons living with HIV (PLWH) and five individual interviews with parents of children living with HIV in the western United States. Although providers were wary about a potential negative impact on consistent engagement in care, they predicted that patients, especially those with adherence challenges, would be enthusiastic about LAI options. Many PLWH, especially young adults, welcomed the option of an LAI-ART regimen; however, others feared injections and expressed concerns about possible side effects, dosing more frequent than every 2 weeks, additional costs, and lower efficacy. Parents' interest varied according to their child's age and sensitivity to injections. In summary, potential users considered LAI-ART generally acceptable yet voiced possible concerns as well, especially if their current pill-based regimen was effective in achieving viral suppression.

Objectives: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos., Methods: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry., Results: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13-2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11-5.29; p=.03)., Conclusions: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163-175).

Objective: To investigate the effect of hepatitis C virus (HCV) on neurocognitive performance in chronically HIV-infected patients enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study., Methods: A total of 1,582 participants in CHARTER who were tested for HCV antibody underwent neurocognitive testing; serum HCV RNA was available for 346 seropositive patients. Neurocognitive performance was compared in 408 HCV-seropositive and 1,174 HCV-seronegative participants and in a subset of 160 seropositive and 707 seronegative participants without serious comorbid neurologic conditions that might impair neurocognitive performance, using linear regression and taking into account HIV-associated and demographic factors (including IV drug use) and liver function., Results: Neurocognitive performance characterized by global deficit scores and the proportion of individuals who were impaired were the same in the HCV-seropositive and HCV-seronegative groups. In univariable analyses in the entire sample, only verbal domain scores showed small statistically different superior performance in the HCV+ group that was not evident in multivariable analysis. In the subgroup without significant comorbidities, scores in all 7 domains of neurocognitive functioning did not differ by HCV serostatus. Among the HCV-seropositive participants, there was no association between neurocognitive performance and serum HCV RNA concentration., Conclusion: In HIV-infected patients, HCV coinfection does not contribute to neurocognitive impairment, at least in the absence of substantial HCV-associated liver damage, which was not evident in our cohort., (© 2014 American Academy of Neurology.)

Background: Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefit patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modified directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom first-line therapy had failed., Methods: We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom first-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modified directly observed therapy or standard of care. Randomisation was stratified by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confirmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569., Findings: Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modified directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modified directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25·1% (95% CI 17·7-32·4) in the modified directly observed therapy group and 17·3% (10·8-23·7) in the standard-of-care group, for a weighted difference in standard of care versus modified directly observed therapy of -6·6% (95% CI -16·5% to 3·2%; p=0·19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modified directly observed therapy group and n=15 in the standard-of-care group)., Interpretation: Partner-based training with modified directly observed therapy had no effect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting., Funding: AIDS Clinical Trials Group and the National Institute of Allergy and Infectious Diseases, US National Institutes of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: We aimed to evaluate treatment responses to atazanavir plus ritonavir (ATV/r) or efavirenz (EFV) in initial antiretroviral regimens among women and men, and determine if treatment outcomes differ by sex., Methods: We performed a randomized trial of open-label ATV/r or EFV combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) in 1857 human immunodeficiency virus type 1-infected, treatment-naive persons enrolled between September 2005 and November 2007 at 59 sites in the United States and Puerto Rico. Associations of sex with 3 primary study endpoints of time to virologic failure, safety, and tolerability events were analyzed using Cox proportional hazards models. Model-based population pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM version VII)., Results: Of 1857 participants, 322 were women. Women assigned to ATV/r had a higher risk of virologic failure with either nucleoside reverse transcriptase inhibitor backbone than women assigned to EFV, or men assigned to ATV/r. The effects of ATV/r and EFV upon safety and tolerability risk did not differ significantly by sex. With ABC/3TC, women had a significantly higher (32%) safety risk compared to men; with TDF/FTC, the safety risk was 20% larger for women compared to men, but not statistically significant. Women had slower ATV clearance and higher predose levels of ATV compared to men. Self-reported adherence did not differ significantly by sex., Conclusions: This is the first randomized clinical trial to identify a significantly earlier time to virologic failure in women randomized to ATV/r compared to women randomized to EFV. This finding has important clinical implications given that boosted protease inhibitors are often favored over EFV in women of childbearing potential., Clinical Trials Registration: NCT00118898.

Milked venoms of Conus demonstrate direct lineage to US Food and Drug Administration approved and present in-trial drug leads. Yet the complexity of the milked venom has not been adequately investigated or characterized, in a sustainable manner. In this study we determine the extent of molecular mass differentiation in milked venom from captive Conus magus and confirm the expression of known conotoxin constituents. We demonstrate the presence of post-translational N-terminal peptide truncation, which differentiates the milked venom constituent α-conotoxin MI from the novel α-conotoxin MIC. This truncation has a direct effect on peptide bioactivity--K(i) of 89.1 ± 9.1 and 248.7 ± 10.9 nM (α-conotoxin MI and MIC respectively) toward the muscle-type nAChR (Torpedo). These milked venom conotoxins demonstrated acute lethality in fish, with a LD₅₀ of 12.24 and 23.29 μg kg⁻¹ for α-conotoxin MI and MIC respectively. By synthesizing and investigating the synthetic intermediate variant des[Gly]¹α-conotoxin MI, it was demonstrated that retention of the N-terminal arginine residue increased affinity at the muscle-type nAChR site (binding Ki of 73.3 ± 5.8 nM and lethal toxicity level LD50 of 8.19 μg kg⁻¹). This post-translational modification event within the milked venom of C. magus represents a unique mechanism by which cone snails are able to increase the chemical and pharmacological diversity of their venoms., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To assess differences in body circumferences and body mass index (BMI, kg/m(2)) between antiretroviral treatment (ART) naïve HIV-infected and HIV-uninfected persons., Methods: Waist, arm, and thigh circumferences and BMI were measured within the ALLRT and NHANES cohorts between 1998 and 2007. ALLRT is a prospective, longitudinal study of U.S. participants enrolled in randomized HIV treatment studies conducted by the AIDS Clinical Trials Group (ACTG). NHANES is a representative group of the US population. The cohorts were analyzed in two time periods, to account for trends towards increased adiposity. Anthropometrics were displayed in percentiles by age and sex. Multiple linear regression models examined differences between cohorts., Results: ALLRT had more males (82% versus 48%, p<0.0001), more black participants (32% versus 23%, p<0.0001), and less Hispanics (21% versus 30%, p<0.0001) than NHANES. Mean BMI was smaller in ALLRT males and females compared to NHANES by 1.6-2.4 kg/m(2) (p<0.0001). Mean waist and arm circumferences in both sexes and time periods were significantly smaller in ALLRT than in NHANES (p<0.0001). Mean thigh circumference in ALLRT was also smaller than NHANES among males (p<0.0001 in both time periods) and females (p = 0.01 in the early time period)., Conclusions: Differences in anthropometrics existed prior to ART initiation, in this large national cohort of HIV-infected individuals, compared to a representative HIV-uninfected cohort, indicating that HIV and its complications have important effects on body shape. Further longitudinal examination of anthropometrics in this HIV-infected cohort may provide additional insight into disease risk., Trial Registration: NCT00001137 at www.clinicaltrials.gov.

Background: Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes., Methods: We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count<350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non-injection drug abuse, alcohol abuse, and mental illness., Results: Among 10,692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend<.001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend<.001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P<.001)., Conclusions: In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide.

Background: The HIV Dementia Scale (HDS) was developed to screen for HIV-associated neurocognitive disorders (HAND), but concerns have persisted regarding its substandard sensitivity. This study aimed to examine the classification accuracy of the HDS using raw and norm-based cut points and to evaluate the contribution of the HDS subtests to predicting HAND., Methods: A total of 1580 HIV-infected participants from 6 US sites completed the HDS, and a gold standard neuropsychological battery, on which 51% of participants were impaired., Results: Sensitivity and specificity to HAND using the standard raw HDS cut point were 24% and 92%, respectively. The raw HDS subtests of attention, recall, and psychomotor speed significantly contributed to classification of HAND, whereas visuomotor construction contributed the least. A modified raw cut point of 14 yielded sensitivity of 66% and specificity of 61%, with cross-validation. Using norms also significantly improved sensitivity to 69% with a concomitant reduction of specificity to 56%, whereas the positive predictive value declined from 75% to 62% and negative predictive value improved from 54% to 64%. The HDS showed similarly modest rates of sensitivity and specificity among subpopulations of individuals with minimal comorbidity and successful viral suppression., Conclusions: Findings indicate that while the HDS is a statistically significant predictor of HAND, particularly when adjusted for demographic factors, its relatively low diagnostic classification accuracy continues to hinder its clinical utility. A raw cut point of 14 greatly improved the sensitivity of the previously established raw cut score, but may be subject to ceiling effects, particularly on repeat assessments.

Background: Despite modern antiretroviral treatment, HIV-associated distal neuropathic pain (DNP) remains one of the most prevalent and debilitating complications of HIV disease. Neuropathic pain is often accompanied by depressed mood, and both pain and depression have been associated with decreased health-related quality of life (HRQOL) well-being. The relative contribution of depression and pain to worse life quality has not been addressed, however, even though a better understanding might sharpen intervention strategies., Methods: We used the Medical Outcomes Study HIV (MOS-HIV) Health Survey and the Beck depression inventory-II and linear regression models to investigate HRQOL well-being in HIV-infected patients with DNP (n = 397) participating in an observational cohort study at six U.S. sites (CNS HIV Antiretroviral Treatment Effects Research Study, CHARTER)., Results: For this sample of patients with HIV DNP, severity of depressed mood was more highly correlated with HRQOL well-being than was pain intensity., Conclusions: These results suggest that interventions to improve HRQOL well-being in individuals with HIV-associated DNP may need to address not only pain intensity but mood state as well., (Published by Elsevier Inc.)

Objective: To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4(+) T-cell counts (CD4 cell counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 cell counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 cell count trajectory accounting for losses-to-follow-up and treatment discontinuations., Design: The study population included 898 US patients first initiating ART in a randomized trial (AIDS Clinical Trials Group 384); 575 were subsequently prospectively followed in an observational study (AIDS Clinical Trials Group Longitudinal Linked Randomized Trials)., Methods: Inverse probability of censoring weighting statistical methods were used to estimate the CD4 cell count trajectory accounting for losses-to-follow-up and ART discontinuations, overall and for pretreatment CD4 cell count categories (500 cells/microl)., Results: Median CD4 cell count increased from 270 cells/microl pre-ART to an estimated 556 cells/microl at 3 and 532 cells/microl at 7 years after starting ART in analyses ignoring treatment discontinuations, and to 570 and 640 cells/microl, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25, 9, 3, and 2% of patients with pretreatment CD4 cell counts of 200 or less, 201-350, 351-500, and more than 500 cells/microl would have had CD4 cell counts of 350 cells/microl or less after 7 years., Conclusion: If patients remain on ART, CD4 cell counts increase in most patients for at least 7 years. However, the substantial percentage of patients starting therapy at low CD4 cell counts who still had low CD4 cell counts after 7 years provides support for ART initiation at higher CD4 cell counts.

BACKGROUND. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. METHODS. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. RESULTS. Median age at first presentation for HIV care increased over time (range, 40-43 years; P < .01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P < .01) and heterosexual transmission risk increased (from 16% to 23%; P < .01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135-517 cells/mm(3)) from 1997 to 2007 (P < .01). The percentage of patients with a CD4 count > or = 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P < .01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). CONCLUSION. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained <350 cells/mm(3), which suggests the urgent need for earlier HIV diagnosis and treatment.

Despite US Public Health Service (USPHS) recommendations for antimicrobial prophylaxis for patients with advanced human immunodeficiency virus (HIV) disease, the proportion of patients who receive prophylaxis is not known. We measured the prevalence of antimicrobial prophylaxis use, and treatment for HIV wasting at baseline among 531 patients with advanced HIV disease enrolled in a multicenter randomized trial of red blood cell transfusion. Use of antimicrobial prophylaxis and treatment for wasting in the 30 days before enrollment was ascertained in patients eligible for primary prophylaxis, secondary prophylaxis, or both, according to USPHS guidelines. There was high utilization of primary and secondary Pneumocystis carinii pneumonia prophylaxis, variability in primary Mycobacterium avium complex prophylaxis by center, and low use of primary cytomegalovirus prophylaxis. Treatment of wasting was more common in white than nonwhite patients and in patients with HIV disease who lived in the region west of the Mississippi River of the United States versus those whose lived in the eastern region.

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.

Background: Institutional variation in the quality of medical care may be evaluated by examining process measures, such as use of diagnostic procedures or treatment modalities, or outcome measures, such as mortality. We undertook this study to examine variations in both process and outcome of care for patients with HIV-related Pneumocystis carinii pneumonia (PCP) at two geographically diverse, HIV-experienced, public municipal hospitals., Design: Retrospective review of hospitalized patients diagnosed as having PCP cared for at two municipal hospitals from 1988 to 1990. At hospital A, charts of all patients diagnosed as having PCP were abstracted (n=209); at hospital B, a random sample of 15% were abstracted (=136)., Results: Among all hospitalized patients diagnosed as having PCP, the frequency of making a definitive diagnosis of PCP (as opposed to treating empirically) differed markedly at the two hospitals (85% in hospital A vs 26% in hospital B; p<0.001), as did the use of intensive care (18% vs 3%; p<0.001) and "do-not-resuscitate" orders (39% vs 14%; p<0.001), although the timing of starting anti-Pneumocystis medications (89% vs 88% within the first 2 hospital days) and the use of corticosteroids (21% vs 23%) were similar. Despite differences in the process of care, survival rates were similar at the two institutions (75% vs 76%; p=0.8) and remained similar when logistic regression was used to control for demographic variables and severity of illness (odds ratio for survival, hospital B vs A, 1.2 [95% confidence interval, 0.7, 2.0]). The 95% confidence intervals (0.7, 2.0), however, were consistent with a considerable (and clinically significant) disparity in survival (from 30% lower to a twofold higher odds of survival). Sample size calculations showed that a sample of 10 cases in each hospital would be required to detect the observed difference in definitive diagnosis rates (85% vs 26%), but 722 cases in each hospital would be required to detect a relevant difference in mortality., Conclusions: The process of care for hospitalized patients with PCP in these two institutions differed considerably, but the survival rates were not significantly different, even after adjusting for confounding factors. While sample sizes available at the individual institutions were sufficient for evaluation of the process of care, they did not provide the power necessary to evaluate outcomes. Comparisons of outcomes such as mortality between individual hospitals may not have the statistical power to exclude important differences.

Background: The acute clinical events surrounding the acquisition of human immunodeficiency virus (HIV) have not been well characterized., Objective: To further define the clinical and epidemiologic presentation of primary HIV infection., Design: Descriptive cohort study., Setting: University research clinic., Patients: 46 adults (43 men and 3 women) with primary HIV infection who enrolled in the study a median of 51 days after HIV seroconversion., Measurements: Documentation of recent HIV seroconversion. Standardized collection of demographic characteristics and sexual contact history, results of tests for HIV RNA, HIV culture, and T-cell subsets., Results: 41 of 46 patients (89%) developed an acute retroviral syndrome. Primary HIV infection was infrequently diagnosed at the initial medical encounter, even in persons enrolled in routine HIV screening programs. Median numbers of sexual partners 6 months and 1 month before acquisition of HIV were three and one, respectively; 21 patients (46%) reported having had only one partner in the month before seroconversion. Of the 12 patients who could identify the precise date of and activity leading to seroconversion, 4 reported having only oral-genital contact., Conclusions: Primary HIV infection causes a recognizable clinical syndrome that is often underdiagnosed, even in persons enrolled in a program of routine surveillance for HIV infection. Frequency of sexual contact and overall numbers of sexual partners in this group of homosexual men who acquired HIV were markedly lower than those seen a decade ago. Acquisition of HIV does occur, even in persons with relatively few sexual partners. Increased attention to oral-genital contact as a means of acquiring HIV appears to be warranted.