Factors Associated With Severity of COVID-19 Disease in a Multicenter Cohort of People With HIV in the United States, March-December 2020.

BACKGROUND: Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies. SETTING: Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care. METHODS: We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores. RESULTS: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm 3 [aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm 3 (aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm 3 , diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died. CONCLUSIONS: PWH with CD4 count <350 cells/mm 3 , and a history of CD4 count <200 cells/mm 3 , have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness.

Factors associated with severity of COVID-19 disease in a multicenter cohort of people with HIV in the United States, March-December 2020.

BACKGROUND: Understanding the spectrum of SARS-CoV-2 infection and COVID-19 disease in people with HIV (PWH) is critical to provide clinical guidance and implement risk-reduction strategies. OBJECTIVE: To characterize COVID-19 in PWH in the United States and identify predictors of disease severity. DESIGN: Observational cohort study. SETTING: Geographically diverse clinical sites in the CFAR Network of Integrated Clinical Systems (CNICS). PARTICIPANTS: Adults receiving HIV care through December 31, 2020. MEASUREMENTS: COVID-19 cases and severity (hospitalization, intensive care, death). RESULTS: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March-December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized and 12 died. PWH with current CD4 count <350 cells/mm 3 (aRR 2.68; 95%CI 1.93-3.71; P<.001) or lowest recorded CD4 count <200 (aRR 1.67; 95%CI 1.18-2.36; P<.005) had greater risk of hospitalization. HIV viral load suppression and antiretroviral therapy (ART) status were not associated with hospitalization, although the majority of PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared to other racial/ethnic groups (aRR 1.51; 95%CI 1.04-2.19, P=.03). Chronic kidney disease (CKD), chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher risk of hospitalization. PWH who were older, not on ART, with current CD4 <350, diabetes, and CKD were overrepresented amongst PWH who required intubation or died. LIMITATIONS: Unable to compare directly to persons without HIV; underestimate of total COVID-19 cases. CONCLUSIONS: PWH with CD4 <350 cells/mm 3 , low CD4/CD8 ratio, and history of CD4 <200, have a clear excess risk of severe COVID-19, after accounting for comorbidities also associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination, early treatment, and monitored closely for worsening illness.

Mind the gap: observation windows to define periods of event ascertainment as a quality control method for longitudinal electronic health record data.

PURPOSE: Use of electronic health records (EHRs) in health research may lead to the false assumption of complete event ascertainment. We estimated "observation windows" (OWs), defined as periods within which the assumption of complete ascertainment of events is more likely to hold, as a quality control approach to reducing the likelihood of this false assumption. We demonstrated the impact of OWs on estimating the rates of type II diabetes mellitus (diabetes) from HIV clinical cohorts. METHODS: Data contributed by 16 HIV clinical cohorts to the NA-ACCORD were used to identify and evaluate OWs for an operationalized definition of diabetes occurrence as a case study. Procedures included (1) gathering cohort-level data; (2) visualizing and summarizing gaps in observations; (3) systematically establishing start and stop dates during which the assumption of complete ascertainment of diabetes events was reasonable; and (4) visualizing the diabetes OWs relative to the cohort open and close dates to identify immortal person-time. We estimated diabetes occurrence event rates and 95% confidence intervals in the most recent decade that data were available (January 1, 2007, to December 31, 2016). RESULTS: The number of diabetes events decreased by 17% with the use of the diabetes OWs; immortal person-time was removed decreasing total person-years by 23%. Consequently, the diabetes rate increased from 1.23 (95% confidence interval [1.20, 1.25]) per 100 person-years to 1.32 [1.29, 1.35] per 100 person-years with the use of diabetes OWs. CONCLUSIONS: As the use of EHR-curated data for event-driven health research continues to expand, OWs have utility as a quality control approach to complete event ascertainment, helping to improve accuracy of estimates by removing immortal person-time when ascertainment is incomplete.

Increased Risk of Myocardial Infarction in HIV-Infected Individuals in North America Compared With the General Population.

BACKGROUND: Previous studies of cardiovascular disease (CVD) among HIV-infected individuals have been limited by the inability to validate and differentiate atherosclerotic type 1 myocardial infarctions (T1MIs) from other events. We sought to define the incidence of T1MIs and risk attributable to traditional and HIV-specific factors among participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and compare adjusted incidence rates (IRs) to the general population Atherosclerosis Risk in Communities (ARIC) cohort. METHODS: We ascertained and adjudicated incident MIs among individuals enrolled in 7 NA-ACCORD cohorts between 1995 and 2014. We calculated IRs, adjusted incidence rate ratios (aIRRs), and 95% confidence intervals of risk factors for T1MI using Poisson regression. We compared aIRRs of T1MIs in NA-ACCORD with those from ARIC. RESULTS: Among 29,169 HIV-infected individuals, the IR for T1MIs was 2.57 (2.30 to 2.86) per 1000 person-years, and the aIRR was significantly higher compared with participants in ARIC [1.30 (1.09 to 1.56)]. In multivariable analysis restricted to HIV-infected individuals and including traditional CVD risk factors, the rate of T1MI increased with decreasing CD4 count [≥500 cells/µL: ref; 350-499 cells/µL: aIRR = 1.32 (0.98 to 1.77); 200-349 cells/µL: aIRR = 1.37 (1.01 to 1.86); 100-199 cells/µL: aIRR = 1.60 (1.09 to 2.34); <100 cells/µL: aIRR = 2.19 (1.44 to 3.33)]. Risk associated with detectable HIV RNA [<400 copies/mL: ref; ≥400 copies/mL: aIRR = 1.36 (1.06 to 1.75)] was significantly increased only when CD4 was excluded. CONCLUSIONS: The higher incidence of T1MI in HIV-infected individuals and increased risk associated with lower CD4 count and detectable HIV RNA suggest that early suppressive antiretroviral treatment and aggressive management of traditional CVD risk factors are necessary to maximally reduce MI risk.

The Role of Current and Historical Alcohol Use in Hepatic Fibrosis Among HIV-Infected Individuals.

We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2-7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5-2.8), diabetes (aOR 2.3, 95% CI 1.8-2.9), current CD4 <200 cells/mm3 (aOR 5.4, 95% CI 4.2-6.9) and HIV RNA >500 copies/mL (aOR 1.3, 95% CI 1.0-1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6-2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1-2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2-2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

Short Communication: Phylogenetic Evidence of HIV-1 Transmission Between Adult and Adolescent Men Who Have Sex with Men.

HIV-1 incidence among youth, especially men who have sex with men (MSM), is increasing in the United States. We aimed to better understand the patterns of adolescent HIV-1 acquisition, to help guide future prevention interventions. We conducted a study combining epidemiologic and HIV-1 pol sequence data from a retrospective cohort of HIV-infected adults and adolescents in Seattle, WA between 2000 and 2013. Adolescents were defined as 13-24 years of age at the time of first HIV-1 care. Maximum-likelihood phylogenetic trees were reconstructed to identify putative viral transmission clusters of two or more individuals, followed by multivariable regression tests of associations between clustering and demographic and clinical parameters. The dataset included 3,102 sequences from 1,953 individuals; 72 putative transmission clusters were identified, representing 168 individuals (8.6%). MSM and MSM/intravenous drug use (IDU) were positively associated with clustering, with aOR 3.18 (95% CI: 1.34-7.55) and 2.59 (95% CI: 1.04-6.49), respectively. African American race was negatively associated with clustering (aOR 0.54 95% CI: 0.32-0.91). Twenty-five clusters contained one adolescent and five clusters contained two adolescents. Other individuals who clustered with adolescents were predominantly male (95%), white (85%), and either MSM (66%) or MSM/IDU (16%), with a greater mean age (34 years vs. 22 years; p < .01). In this Seattle cohort, HIV-1 transmission linkages were identified between white male adolescents and older MSM adults. Interventions aimed at age-discrepant pairs may reduce HIV-1 infections in adolescent males.

Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis.

BACKGROUND: Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression. METHODS: We determined the incidence and predictors of advanced hepatic fibrosis measured by the Fibrosis-4 index (≥3.25) in a large diverse population of HIV-infected patients without significant liver disease at baseline (Fibrosis-4 score <1.45) in care between January 2000 and March 2014. We used Cox proportional hazards analysis to examine factors associated with progression to Fibrosis-4 score ≥3.25. RESULTS: Among 14,198 HIV-infected patients, hepatitis C virus (HCV) coinfection [adjusted hazard ratio (aHR) 1.9, 95% confidence interval (CI): 1.6 to 2.1], hepatitis B virus coinfection (aHR 1.5, 95% CI: 1.2 to 1.8), alcohol-use disorder (aHR 1.4, 95% CI: 1.2 to 1.6), and diabetes (aHR 1.9, 95% CI: 1.6 to 2.3) were associated with progression to advanced fibrosis in multivariable analysis. In addition, patients at each lower level of time-varying CD4 cell count had a significantly greater risk of progression, with ∼7-fold higher risk in those with CD4 <100 cells per cubic millimeter (aHR 6.9, 95% CI: 5.8 to 8.3) compared with CD4 ≥500 cells per cubic millimeter. An increasing gradient of risk was also observed among patients with higher time-varying HIV viral load (VL), with the greatest risk noted with VL ≥100,000 copies per milliliter (aHR 2.6, 95% CI: 2.2 to 3.1) compared with VL <500 copies per milliliter. CONCLUSIONS: Lower CD4 cell count and higher HIV VL were significantly associated with progression to advanced hepatic fibrosis in a dose-dependent manner, independent of the risk associated with traditional factors: hepatitis C virus or hepatitis B virus coinfection, alcohol, and diabetes. Our findings suggest that early treatment of HIV infection could mitigate liver disease.

Using observational data to emulate a randomized trial of dynamic treatment-switching strategies: an application to antiretroviral therapy.

Background: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy). Methods: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting. Results: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death. Conclusions: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.

Ascertainment and verification of end-stage renal disease and end-stage liver disease in the north american AIDS cohort collaboration on research and design.

The burden of HIV disease has shifted from traditional AIDS-defining illnesses to serious non-AIDS-defining comorbid conditions. Research aimed at improving HIV-related comorbid disease outcomes requires well-defined, verified clinical endpoints. We developed methods to ascertain and verify end-stage renal disease (ESRD) and end-stage liver disease (ESLD) and validated screening algorithms within the largest HIV cohort collaboration in North America (NA-ACCORD). Individuals who screened positive among all participants in twelve cohorts enrolled between January 1996 and December 2009 underwent medical record review to verify incident ESRD or ESLD using standardized protocols. We randomly sampled 6% of contributing cohorts to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ESLD and ESRD screening algorithms in a validation subcohort. Among 43,433 patients screened for ESRD, 822 screened positive of which 620 met clinical criteria for ESRD. The algorithm had 100% sensitivity, 99% specificity, 82% PPV, and 100% NPV for ESRD. Among 41,463 patients screened for ESLD, 2,024 screened positive of which 645 met diagnostic criteria for ESLD. The algorithm had 100% sensitivity, 95% specificity, 27% PPV, and 100% NPV for ESLD. Our methods proved robust for ascertainment of ESRD and ESLD in persons infected with HIV.

Factors associated with delayed hepatitis B viral suppression on tenofovir among patients coinfected with HBV-HIV in the CNICS cohort.

BACKGROUND: Despite widespread use in HIV and hepatitis B virus (HBV) infection, the effectiveness of tenofovir (TDF) has not been studied extensively outside of small cohorts of coinfected patients with HBV-HIV. We examined the effect of prior lamivudine (3TC) treatment and other factors on HBV DNA suppression with TDF in a multisite clinical cohort of coinfected patients. METHODS: We studied all patients enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort from 1996 to 2011 who had chronic HBV and HIV infection, initiated a TDF-based regimen continued for ≥ 3 months and had on-treatment HBV DNA measurements. We used Kaplan-Meier curves and Cox-proportional hazards to estimate time to suppression (HBV DNA level <200 IU/mL or <1000 copies/mL) by selected covariates. RESULTS: Among 397 coinfected patients on TDF, 91% were also on emtricitabine or 3TC concurrently, 92% of those tested were hepatitis B e antigen positive, 196 (49%) had prior 3TC exposure; 192 (48%) achieved HBV DNA suppression over a median of 28 months (interquartile range: 13-71). Median time to HBV DNA suppression was 17 months for those who were 3TC-naive and 50 months for those who were 3TC exposed. After controlling for other factors, prior 3TC exposure, baseline HBV DNA level >10,000 IU/mL, and lower nadir CD4 count were independently associated with decreased likelihood of HBV DNA suppression on TDF. CONCLUSIONS: These results emphasize the role of prior 3TC exposure and immune response on delayed HBV suppression on TDF.

High levels of antiretroviral use and viral suppression among persons in HIV care in the United States, 2010.

BACKGROUND: Contemporary data on patterns of antiretroviral therapy (ART) use in the United States are needed to inform efforts to improve the HIV care cascade. METHODS: We conducted a cross-sectional study of patients in the Centers for AIDS Research Network of Integrated Clinical Systems cohort who were in HIV care in 2010 to assess ART use and outcomes, stratified by nadir CD4 count (≤350, 351-500, or >500 cells/mm), demographics, psychiatric diagnoses, substance use, and engagement in continuous care (≥2 visits ≥3 months apart in 2010). RESULTS: Of 8633 patients at 7 sites who had ≥1 medical visit and ≥1 viral load in 2010, 94% had ever initiated ART, 89% were on ART, and 70% had an undetectable viral load at the end of 2010. Fifty percent of ART-naive patients had nadir CD4 counts >500 cells per cubic millimeter, but this group comprised just 3% of the total population. Among patients who were ART naive at the time of cohort entry (N = 4637), both ART initiation and viral suppression were strongly associated with nadir CD4 count. Comparing 2009 and 2010, the percentages of patients with viral suppression among those with nadir CD4 counts 351-500 and >500 cells per cubic millimeter were 44% vs. 57% and 25% vs. 33%, respectively. Engagement in care was the only factor consistently associated with ART use and viral suppression across nadir CD4 count strata. CONCLUSIONS: Our findings suggest that ART use and viral suppression among persons in HIV care may be more common than estimated in some previous studies and increased from 2009 to 2010.

Impact of NRTIs on lipid levels among a large HIV-infected cohort initiating antiretroviral therapy in clinical care.

OBJECTIVE: to assess the associations between nucleoside reverse transcriptase inhibitors (NRTIs) and change in lipid levels among a large cohort of HIV-infected patients in routine clinical care initiating their first potent antiretroviral regimen. DESIGN: longitudinal observational cohort study from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS: we used generalized estimating equations to examine the association between NRTIs and lipids accounting for within-patient correlations between repeated measures and key clinical and demographic characteristics including other antiretroviral medications. RESULTS: among 2267 individuals who started their first antiretroviral regimen, tenofovir with emtricitabine or lamivudine was associated with lower levels for total cholesterol, low-density lipoprotein (LDL), triglycerides, non-high-density lipoprotein (HDL), and HDL, compared with other NRTI pairs in adjusted analyses. LDL levels were highest among patients receiving didanosine/lamivudine. Triglyceride levels were highest in stavudine/lamivudine users. HDL levels were highest among patients receiving didanosine/stavudine. Hepatitis C infection and younger age were also associated with lower lipid levels. CONCLUSION: we found clinically important heterogeneity within the NRTI class of antiretroviral medications regarding their effect on lipid levels over time. Although the lipid profile of tenofovir with emtricitabine or lamivudine appeared to be less pro-atherogenic in this large longitudinal study of HIV-infected patients in routine clinical care, there was no association with beneficial HDL levels. In general, the change in lipid levels associated with most antiretroviral agents, particularly those NRTI combinations currently in common use, are relatively modest. Additional studies are needed to understand the long-term implications of these findings on cardiovascular disease risk.

Late presentation for human immunodeficiency virus care in the United States and Canada.

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.

Effect of early versus deferred antiretroviral therapy for HIV on survival.

BACKGROUND: The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS: We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS: In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS: The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons.

Protective response rates to hepatitis B (HB) vaccination have been reported as low as 18-62% in HIV-infected persons. The relative importance of various predictors for this poor response has not been fully characterized. In this retrospective cohort study, we examined the relationship between clinical characteristics and vaccine non-response (HB surface antibody <10 IU/L) among patients attending an urban HIV clinic. Among the 97 patients who met the inclusion criteria, 43 (44%) developed a protective antibody response. In multivariate analyses, age >40 years (odds ratio [OR] 3.03 [95% confidence interval [CI], 1.14-8.06]; P = 0.026) and alcohol abuse (OR 4.92 [95% CI, 1.72-20.89]; P = 0.007) were independent predictors of failure to develop vaccine response. In addition, CD4 nadir <200 (OR 7.24 [95% CI, 1.91-27.41]; P = 0.004), rather than CD4 current to vaccination, remained a strong independent risk factor. Patients with HIV viral suppression on highly active antiretroviral therapy had a significantly lower rate of vaccine failure (OR 0.31 [95% CI, 0.11-0.91]; P = 0.033), after adjusting for these other covariates. Our findings underscore the importance of confirming seroconversion after HB vaccination in HIV-infected patients and initiating vaccination early in the course of HIV infection.

Persistent Kaposi sarcoma in the era of highly active antiretroviral therapy: characterizing the predictors of clinical response.

OBJECTIVES: To evaluate the role of highly active antiretroviral therapy and chemotherapy on tumor response among persons with AIDS-related Kaposi sarcoma and identify factors associated with response in a clinic setting. DESIGN: Retrospective cohort. METHODS: One hundred and fourteen patients from two HIV clinics with a diagnosis of Kaposi sarcoma were identified via a clinical database. Records were reviewed to confirm Kaposi sarcoma diagnosis and abstract clinical and chemotherapy information. Demographics, laboratory values, and highly active antiretroviral therapy use were abstracted electronically. Cox's proportional hazards models identified predictors of Kaposi sarcoma improvement and resolution. RESULTS: Thirty-six months following Kaposi sarcoma diagnosis, the rate of improvement among 64 patients with confirmed Kaposi sarcoma was 77% and that of complete resolution was 51%. In univariate analyses, recent chemotherapy was associated with Kaposi sarcoma improvement, and recent HIV viral load and highly active antiretroviral therapy were associated with both improvement and resolution. No measured baseline characteristics (tumor stage, diagnosis year, CD4 T-cell count, HIV viral load, or prior highly active antiretroviral therapy history) or recent CD4 T-cell counts predicted improvement or resolution. In multivariate analyses, recent chemotherapy (hazard ratio 5.5, 95% confidence interval: 2.7-11.2, P < 0.001) and highly active antiretroviral therapy (hazard ratio 4.1, 95% confidence interval: 1.4-12.6, P = 0.01) were predictors of improvement; only recent highly active antiretroviral therapy was associated with resolution (hazard ratio 6.2, 95% confidence interval: 1.5-26.4, P = 0.01). Response was not associated with type of highly active antiretroviral therapy regimen (non nucleoside reverse transcriptase inhibitor based, protease inhibitor based, or ritonavir-boosted protease inhibitor based). CONCLUSION: Highly active antiretroviral therapy and chemotherapy are important in clinical Kaposi sarcoma response. Despite widespread availability of these therapies, Kaposi sarcoma continues to be a clinical problem; only half the patients achieved complete resolution of disease. New therapeutic approaches are needed.

Initiating highly active antiretroviral therapy with newer protease inhibitors is associated with better survival compared to first-generation protease inhibitors or nevirapine.

The high prevalence of comorbidity among HIV-infected patients in care such as hepatitis C virus (HCV) coinfection and mental illness may contribute to increased toxicity and decreased adherence to highly active antiretroviral therapy (HAART). Newer HAART regimens have less toxicity and better dosing characteristics than first-generation regimens, but it is not known whether they are associated with improved clinical outcomes. The purpose of this study was to examine the effect of patient factors and initial HAART regimen on survival among HIV-infected patients in routine care. We conducted an observational study of all HAART-naïve patients in the University of Washington HIV cohort who initiated HAART between January 1996 and October 2005. Cox survival analyses were used to examine the association between time to death and treatment with first-generation protease inhibitors (PIs; indinavir, ritonavir, saquinavir), newer PIs (amprenavir, atazanavir, lopinavir, nelfinavir), efavirenz, or nevirapine, controlling for baseline characteristics, and calendar period. Of 694 patients, 84 (12%) died. In adjusted analyses, patients treated with a first-generation PI (hazard ratio [HR] 1.9, p = 0.04) or nevirapine (HR 2.0, p = 0.046) had twice the risk of death compared with those receiving a newer PI. Survival for patients treated with efavirenz did not differ from those receiving a newer PI (HR 1.1, p = 0.8). Greater disease severity (HR 1.7, p = 0.03), hepatitis C virus (HCV; HR 1.6, p = 0.05), and depression (HR 2.0, p = 0.007) were independent predictors of increased mortality. This study demonstrates significant improvement in survival among patients initiating HAART with newer PIs compared to first-generation PIs or nevirapine, and highlights the complexity of patient factors affecting the clinical outcomes of treatment.

Antiretroviral medications associated with elevated blood pressure among patients receiving highly active antiretroviral therapy.

OBJECTIVE: To examine the effect of antiretroviral agents and clinical factors on the development of elevated blood pressure (BP). METHODS: Observational cohort study of patients initiating their first HAART regimen. We evaluated mean BP prior to HAART and while receiving HAART in relation to antiretroviral classes and individual agents, and demographic and clinical characteristics including change in body mass index (BMI) while on HAART. We used logistic regression analysis to examine factors associated with elevated BP [> or = 10 mmHg increase in systolic BP (SBP), diastolic BP (DBP) or new diagnosis of hypertension]. RESULTS: Among 444 patients who had 4592 BP readings, 95 patients developed elevated SBP (n = 83), elevated DBP (n = 33), or a new diagnosis of hypertension (n = 11) after initiating HAART. In multivariate analysis, patients on lopinavir/ritonavir had the highest risk of developing elevated BP [odds ratio (OR), 2.5; P = 0.03] compared with efavirenz-based regimens. When change in BMI was added to the model, increased BMI was significantly associated with elevated BP (OR, 1.3; P = 0.02), and the association between lopinavir/ritonavir and elevated BP was no longer present. Compared with lopinavir/ritonavir-based regimens, patients receiving atazanavir (OR, 0.2; P = 0.03), efavirenz (OR, 0.4; P = 0.02), nelfinavir (OR, 0.3; P = 0.02), or indinavir (OR, 0.3; P = 0.01) had significantly lower odds of developing elevated BP. CONCLUSIONS: Treatment with lopinavir/ritonavir is significantly associated with elevated BP, an effect that appears to be mediated through an increase in BMI. Patients receiving atazanavir were least likely to develop elevated BP. The impact of antiretroviral medications on cardiovascular disease risk factors will increasingly influence treatment decisions.