Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

BACKGROUND: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. METHODS AND RESULTS: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). CONCLUSIONS: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Stockholm City's Elderly Care and Covid19: Interview with Barbro Karlsson.

Upwards of 70% of the Covid19 death toll in Sweden has been people in elderly care services (as of mid-May 2020). We summarize the Covid19 tragedy in elderly care in Sweden, particularly in the City of Stockholm. We explain the institutional structure of elderly care administration and service provision. Those who died of Covid19 in Stockholm's nursing homes had a life-remaining median somewhere in the range of 5 to 9 months. Having contextualized the Covid19 problem in City of Stockholm, we present an interview of Barbro Karlsson, who works at the administrative heart of the Stockholm elderly care system. Her institutional knowledge and sentiment offer great insight into the concrete problems and challenges. There are really two sides to the elderly care Covid19 challenge: The vulnerability and frailty of those in nursing homes and the problem of nosocomial infection-that is, infection caused by contact with others involved in the elderly care experience. The problem calls for targeted solutions by those close to the vulnerable individuals.

Colorectal Cancer Screening in People With and Without HIV in an Integrated Health Care Setting.

BACKGROUND: As people with HIV (PWH) live longer, age-appropriate colorectal cancer (CRC) screening is increasingly important. Limited data exist on CRC screening and outcomes comparing PWH and persons without HIV. SETTING: Large integrated health care system. METHODS: This study included PWH and demographically matched persons without HIV who were aged 50-75 years during 2005-2016 and had no previous CRC screening. We evaluated time to first CRC screening (fecal test, sigmoidoscopy, or colonoscopy). We also assessed detection of adenoma and CRC with sigmoidoscopy or colonoscopy by HIV status, accounting for CRC risk factors including sex, age, race/ethnicity, number of outpatient visits, smoking, body mass index, type-2 diabetes, and inflammatory bowel disease. Among PWH, we evaluated whether CD4 count (<200/200-499/≥500 cells/µL) was associated with adenoma and CRC. RESULTS: Among 3177 PWH and 29,219 persons without HIV, PWH were more likely to be screened (85.6% vs. 79.1% within 5 years, P < 0.001). Among those with sigmoidoscopy or colonoscopy, adenoma was detected in 161 (19.6%) PWH and 1498 (22.6%) persons without HIV, and CRC was detected in 4 (0.5%) PWH and 69 (1.0%) persons without HIV. In adjusted analyses, we found no difference in prevalence of either adenoma or CRC by HIV status (adjusted prevalence ratio = 0.97, 95% confidence interval: 0.83 to 1.12). Lower CD4 count did not increase likelihood of adenoma or CRC. CONCLUSIONS: Within an integrated health care system with an organized CRC screening program, we found no disparities in CRC screening uptake or outcomes among people with and without HIV, and CD4 count did not influence CRC risk among PWH.

Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies.

BACKGROUND: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes. METHODS: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (<200 cells per µL), detectable plasma HIV RNA (>400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented. FINDINGS: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13-35) of these cancers and 37% (7-66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30-58) for cholesterol and 42% (28-56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17-48). For renal disease, the PAF was greatest for hypertension (39%; 26-51) followed by elevated total cholesterol (22%; 13-31), detectable HIV RNA (19; 9-31), and low CD4 cell count (13%; 4-21). INTERPRETATION: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care. FUNDING: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

Impact of Alternative Encounter Types on HIV Viral Suppression Rates in an Integrated Health System.

Kaiser Permanente Mid-Atlantic States (KPMAS) members are increasingly utilizing electronic encounter types, such as telephone appointments and secure messaging for healthcare purposes, although their impact on health outcomes is unknown. We evaluated whether use of alternative encounters by adult human immunodeficiency virus (HIV)-infected patients affected the likelihood of achieving viral suppression (VS). Our study population of 3114 patients contributed 6520 patient-years between 2014 and 2016. We compared VS (HIV RNA <200 copies/mL) by number of in-person visits (1 or ≥2), with further stratification for additional phone and/or e-mail encounters (none, phone only, e-mail only, and both phone and e-mail). Rate ratios (RRs) for VS by number of in-person visits and encounter types were obtained from Poisson modeling, adjusting for age, sex, race/ethnicity, and HIV risk. Compared to those with ≥2 visits, patients with one in-person visit alone were significantly less likely to achieve VS (RR = 0.93; 95% confidence interval, CI: [0.87-1.00]), as were those with one in-person visit plus a telephone encounter (0.93; [0.90-0.97]). We did not find significant differences in VS comparing patients with one in-person visit plus e-mail only (RR = 1.00; 95% CI: [0.97-1.02]) or plus e-mail and telephone (0.99; [0.97-1.01]) to those with ≥2 in-person visits. If supplemented by e-mail communications (with or without telephone contact), patients with one in-person visit per year had similar estimated rates of VS compared with ≥2 in-person visits. More research is needed to know if these findings apply to other care systems.

Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV.

BACKGROUND: There is persistent confusion as to whether abacavir (ABC) increases the risk of myocardial infarction (MI), and whether such risk differs by type 1 (T1MI) or 2 (T2MI) MI in adults with HIV. METHODS: Incident MIs in North American Cohort Collaboration on Research and Design participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude hazard ratio (HR) and adjusted hazard ratio (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately. A sensitivity analysis evaluated whether Framingham risk score (FRS) modified the effect of ABC on MI occurrence. RESULTS: Eight thousand two hundred sixty-five adults who initiated antiretroviral therapy contributed 29,077 person-years and 123 MI events (65 T1MI and 58 T2MI). Median follow-up time was 2.9 (interquartile range 1.4-5.1) years. ABC initiators were more likely to have a history of injection drug use, hepatitis C virus infection, hypertension, diabetes, impaired kidney function, hyperlipidemia, low (<200 cells/mm) CD4 counts, and a history of AIDS. The risk of the combined MI outcome was greater for persons who used ABC in the previous 6 months [aHR = 1.84 (1.17-2.91)]; and persisted for T1MI (aHR = 1.62 [1.01]) and T2MI [aHR = 2.11 (1.08-4.29)]. FRS did not modify the effect of ABC on MI (P = 0.14) and inclusion of FRS in the MSM did not diminish the effect of recent ABC use on the combined outcome. CONCLUSIONS: Recent ABC use was associated with MI after adjustment for known risk factors and for FRS. However, screening for T1MI risks may not identify all or even most persons at risk of ABC use-associated MIs.

Prevalence of Drug-Resistant Minority Variants in Untreated HIV-1-Infected Individuals With and Those Without Transmitted Drug Resistance Detected by Sanger Sequencing.

Minority variant human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are associated with an increased risk of virological failure during treatment with NNRTI-containing regimens. To determine whether individuals to whom variants with isolated NNRTI-associated drug resistance were transmitted are at increased risk of virological failure during treatment with a non-NNRTI-containing regimen, we identified minority variant resistance mutations in 33 individuals with isolated NNRTI-associated transmitted drug resistance and 49 matched controls. We found similar proportions of overall and nucleoside reverse transcriptase inhibitor-associated minority variant resistance mutations in both groups, suggesting that isolated NNRTI-associated transmitted drug resistance may not be a risk factor for virological failure during treatment with a non-NNRTI-containing regimen.

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.

Immunodeficiency, AIDS-related pneumonia, and risk of lung cancer among HIV-infected individuals.

OBJECTIVE: The objective is to clarify the role of immunodeficiency and pneumonia in elevated lung cancer risk among HIV-infected individuals. DESIGN: Cohort study of HIV-infected and HIV-uninfected adults in a large integrated healthcare system in California during 1996-2011. METHODS: We used Poisson models to obtain rate ratios for lung cancer associated with HIV infection, overall and stratified by recent CD4 cells/µl (HIV-uninfected as reference group), with χ tests for trends across CD4 strata. Fully adjusted models included demographics, cancer risk factors (smoking, drug/alcohol abuse, overweight/obesity), and prior pneumonia. RESULTS: Among 24 768 HIV-infected and 257 600 HIV-uninfected individuals, the lung cancer rate per 100 000 person-years was 66 (n = 80 events) for HIV-infected and 33 (n = 506 events) for HIV-uninfected individuals [rate ratio 2.0, 95% confidence interval (CI): 1.7-2.2]. Overall, HIV-infected individuals were at increased risk of lung cancer after adjustment for demographics and cancer risk factors (rate ratio 1.4, 95% CI: 1.1-1.7), but not after additional adjustment for pneumonia (rate ratio 1.2, 95% CI: 0.9-1.6). Lower CD4 cell counts were associated with higher risk of lung cancer in unadjusted and demographics-adjusted models (P < 0.001 for all), but this trend did not remain after adjustment for cancer risk factors and pneumonia. Compared with HIV-uninfected individuals, HIV-infected individuals with CD4 less than 200 cells/µl were not at increased risk of lung cancer in fully adjusted models. CONCLUSION: The increased lung cancer risk among HIV patients is attributable to differences in demographics, risk factors such as smoking, and history of pneumonia. Immunodeficiency does not appear to have an independent effect on lung cancer risk.

Invasive Pneumococcal Disease Among HIV-Infected and HIV-Uninfected Adults in a Large Integrated Healthcare System.

It is unclear whether HIV-infected individuals remain at higher risk of invasive pneumococcal disease (IPD) compared with HIV-uninfected individuals. We conducted a cohort study of HIV-infected and demographically matched HIV-uninfected adults within Kaiser Permanente Northern California during the period 1996-2011. We used Poisson models to obtain rate ratios (RRs) for incident IPD associated with HIV infection and other risk factors. Among 13,079 HIV-infected and 137,643 HIV-uninfected adults, the IPD rate per 100,000 person-years was 160 (n = 109 events) for HIV-infected and 8 (n = 75 events) for HIV-uninfected subjects, with an adjusted RR of 13.0 [95% confidence interval (CI): 9.1-18.7]. For HIV-infected individuals, IPD incidence per 100,000 person-years decreased by 71% during study follow-up, from 305 in 1996-1999 to 88 in 2010-2011 (p < 0.001), with an adjusted RR of 6.6 (95% CI: 2.7-16.1) compared with HIV-uninfected subjects in 2010-2011. Risk factors for IPD among HIV-infected individuals included black compared with white race/ethnicity, smoking, cancer, and higher HIV RNA levels. The 23-valent pneumococcal polysaccharide vaccination was not associated with a reduced risk of IPD in HIV-infected or HIV-uninfected individuals. Among HIV-infected IPD cases, the most common serotype was 19A (33%), and 59% of serotypes were covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Despite a dramatic decline in IPD incidence for HIV-infected adults since 1996, IPD rates were nearly sevenfold higher compared with HIV-uninfected adults in recent years, even after adjustment for risk factors. Timely antiretroviral therapy initiation, risk reduction strategies, and recent guidelines recommending PCV13 use may further reduce IPD incidence among HIV patients.

Narrowing the Gap in Life Expectancy Between HIV-Infected and HIV-Uninfected Individuals With Access to Care.

BACKGROUND: It is unknown if a survival gap remains between HIV-infected and HIV-uninfected individuals with access to care. METHODS: We conducted a cohort study within Kaiser Permanente California during 1996-2011, using abridged life tables to estimate the expected years of life remaining ("life expectancy") at age 20. RESULTS: Among 24,768 HIV-infected and 257,600 HIV-uninfected individuals, there were 2229 and 4970 deaths, with mortality rates of 1827 and 326 per 100,000 person-years, respectively. In 1996-1997, life expectancies at age 20 for HIV-infected and HIV-uninfected individuals were 19.1 and 63.4 years, respectively, corresponding with a gap of 44.3 years (95% confidence interval: 38.4 to 50.2). Life expectancy at age 20 for HIV-infected individuals increased to 47.1 years in 2008 and 53.1 years by 2011, narrowing the gap to 11.8 years (8.9-14.8 years) in 2011. In 2008-2011, life expectancies at age 20 for HIV-infected individuals ranged from a low of 45.8 years for blacks and 46.0 years for those with a history of injection drug use to a high of 52.2 years for Hispanics. HIV-infected individuals who initiated antiretroviral therapy with CD4 ≥500 cells per microliter had a life expectancy at age 20 of 54.5 years in 2008-2011, narrowing the gap relative to HIV-uninfected individuals to 7.9 years (5.1-10.6 years). For these HIV-infected individuals, the gap narrowed further in subgroups with no history of hepatitis B or C infection, smoking, drug/alcohol abuse, or any of these risk factors. CONCLUSIONS: Even with early treatment and access to care, an 8-year gap in life expectancy remains for HIV-infected compared with HIV-uninfected individuals.

Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance.

BACKGROUND: Nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance. METHODS: We reviewed treatment outcomes in a cohort of HIV-1-infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression. RESULTS: Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01). CONCLUSIONS: Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered.

Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals.

BACKGROUND: Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction. METHODS: We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m). RESULTS: Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0). CONCLUSIONS: Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status.

Hepatitis C virus (HCV) co-infection and biological sex may each affect response to antiretroviral therapy (ART), yet no studies have examined HIV-associated outcomes by both HCV status and sex. We conducted a cohort study of HIV-infected adults initiating ART in Kaiser Permanente California during 1996-2011. We used piecewise linear regression to assess CD4 changes by sex and HCV status over 5 years. We used Cox regression to estimate hazard ratios (HR) by sex and HCV status for HIV RNA <500 copies/mL over 1 year, and for AIDS and death over the follow-up period. Among 12,865 subjects, there were 154 HIV/HCV-co-infected women, 1000 HIV/HCV-co-infected men, 1088 HIV-mono-infected women, and 10,623 HIV-mono-infected men. CD4 increases were slower in the first year for HIV/HCV-co-infected women (75 cells/µL) and men (70 cells/µL) compared with HIV-mono-infected women (145 cells/µL) and men (120 cells/µL; p<0.001). After 5 years, women had higher CD4 than men in both HIV-mono-infected (598 vs. 562 cells/µL, p=0.003) and HIV/HCV-co-infected individuals (567 vs. 509 cells/µL, p=0.003). Regardless of sex, HIV/HCV co-infection was associated with 40% higher mortality [95% confidence interval (CI): 1.2-1.6] compared with HIV mono-infection, but was not associated with AIDS (HR 1.1, 95% CI: 0.9-1.3) or achieving HIV RNA <500 copies/mL (HR 1.0, 95% CI: 0.9-1.1). HIV/HCV-co-infected men and women have slower CD4 recovery after starting ART and have increased mortality compared with HIV-mono-infected men and women. HCV should be aggressively treated in HIV/HCV-co-infected adults, regardless of sex.

Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care.

Concerns remain for an increased myocardial infarction (MI) risk among individuals infected with human immunodeficiency virus (HIV). We conducted a cohort study evaluating MI risk from 1996 to 2011 by HIV status. The adjusted MI rate ratio for HIV status declined over time, reaching 1.0 (95% confidence interval, .7-1.4) in 2010-2011, the most recent study period.

HIV infection and incidence of ischemic stroke.

OBJECTIVE: To determine the association of HIV infection and immunodeficiency with incidence of ischemic stroke. DESIGN: Cohort study of HIV-positive and matched HIV-negative adult Kaiser Permanente Northern and Southern California (KPNC and KPSC, respectively) members during 1996-2011 (KPNC) or 2000-2011 (KPSC). METHODS: We used Poisson models to obtain rate ratios for incident ischemic stroke associated with HIV infection, both overall and stratified by CD4 cell counts (cells/µl) and HIV RNA copies (copies/ml), with HIV-negative individuals as the reference group. We also obtained rate ratios for risk factors in the HIV-positive subset. RESULTS: Among 24,768 HIV-positive and 257,600 HIV-negative individuals, the ischemic stroke rate per 100,000 person-years was 125 (n = 151 events) for HIV-positive and 74 (n = 1128 events) for HIV-negative individuals, with an adjusted rate ratio of 1.4 [95% confidence interval (CI) 1.2-1.7). Compared with HIV-negative individuals, HIV-positive individuals with recent CD4 cell counts of 500 cells/µl at least (rate ratio 1.0, 95% CI 0.8-1.4) or recent HIV RNA less than 500 copies/ml (rate ratio 1.1, 95% CI 0.9-1.4) had no excess risk of ischemic stroke, with similar results for HIV-positive individuals with nadir CD4 cell counts of 500 cells/µl at least (rate ratio 1.4, 95% CI 0.8-2.2) or 200-499 cells/µl (rate ratio 1.2, 95% CI 0.9-1.5). Among HIV-positive individuals only, recent CD4 cell count less than 200 cells/µl (rate ratio 2.5, 95% CI 1.3-4.6) was associated with an increased risk of ischemic stroke after adjustment for recent HIV RNA and nadir CD4 cell count, whereas recent HIV RNA and nadir CD4 were not independent risk factors. CONCLUSION: Ischemic stroke incidence in HIV-positive individuals with high CD4 cell count or low HIV RNA is similar to that of HIV-negative individuals.

Prostate cancer incidence and prostate-specific antigen testing among HIV-positive and HIV-negative men.

BACKGROUND: We investigated whether the reported lower incidence of prostate cancer in HIV-positive men is a result of confounding factors or reduced screening. METHODS: We conducted a cohort study of 17,424 HIV-positive and 182,799 HIV-negative men enrolled in Kaiser Permanente (KP). Subjects were followed from the first KP enrollment after January 01, 1996 for KP Northern California (KPNC) and January 01, 2000 for KP Southern California until the earliest of prostate cancer diagnosis, loss to follow-up, or December 31, 2007. Poisson regression was used to compare cancer rates by HIV status adjusting for age, race, smoking, alcohol/drug abuse, overweight/obesity, and diabetes. For the KPNC subset, we analyzed additional available data by HIV status on testosterone deficiency, and on prostate-specific antigen (PSA) tests as a proxy for cancer screening. RESULTS: The prostate cancer incidence rate was 102/100,000 person-years in HIV-positive men (n = 74 cases) and 131/100,000 person-years in HIV-negative men (n = 1195 cases), with an adjusted rate ratio of 0.73 (95% confidence interval: 0.57 to 0.92; P = 0.008). The reduced risk among HIV-positive men was greater for higher-stage cancers, which are less likely to be biased by screening differences than lower-stage cancers. In the KPNC subset, more HIV-positive (90.8%) than HIV-negative men (86.2%) received a PSA test by age 55 (P < 0.001). Decreased risk for HIV-positive men remained when examined only among those with a previous PSA test, and with adjustment for testosterone deficiency (rate ratio = 0.55; 95% confidence interval: 0.39 to 0.80; P = 0.001). CONCLUSIONS: Prostate cancer incidence rates are lower in HIV-positive compared with HIV-negative men, which is not explained by screening differences or the risk factors evaluated.

Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care.

BACKGROUND: We sought to clarify the association of HIV infection and immunodeficiency on myocardial infarction (MI) risk. METHODS: We conducted a cohort study from 1996 to 2009 of HIV-positive (HIV) and demographically matched HIV-negative (HIV) Kaiser Permanente California health plan members. Rate ratios (RRs) were obtained from Poisson regression models comparing MI incidence rates between HIV (overall and stratified by recent and nadir CD4 count, and recent HIV RNA levels) and HIV subjects, adjusting for age, sex, calendar era, race/ethnicity, census-based socioeconomic status, smoking, alcohol/drug abuse, overweight/obesity, diabetes, hypertension, and lipid-lowering therapy. Among HIV subjects, we also evaluated the independent association of CD4, HIV RNA, and antiretroviral therapy (ART) use. RESULTS: The study population included 22,081 HIV and 230,069 HIV subjects. The crude MI incidence rate per 100,000 person-years was 283 and 165 for HIV and HIV subjects, respectively, with an adjusted RR of 1.4 [95% confidence interval (CI): 1.3 to 1.6]. Compared with HIV subjects (reference), MI rates were similar for HIV subjects with recent CD4 ≥500 cells per microliter (RR = 1.18; 95% CI: 0.96 to 1.45) and those with nadir CD4 ≥500 cells per microliter (RR = 0.85; 95% CI: 0.55 to 1.33). Among HIV subjects, nadir CD4 was the only HIV-specific factor associated with MIs (RR per 100 cells = 0.88; 95% CI: 0.81 to 0.96), whereas recent CD4 and HIV RNA, prior ART use, and duration of protease inhibitors and nonnucleoside reverse transcriptase inhibitors were not associated with MIs. CONCLUSION: HIV subjects with recent or nadir CD4 ≥500 cells per microliter had similar MI rates compared with HIV subjects. Lower nadir CD4, in particular, seems to be independently associated with MIs. These results strengthen recommendations for earlier ART initiation.

Missed office visits and risk of mortality among HIV-infected subjects in a large healthcare system in the United States.

Linkage and retention in care soon after HIV diagnosis improves clinical outcomes. Conversely, missed visits after diagnosis are associated with increased mortality in the public care setting. We analyzed mortality among newly diagnosed HIV patients ≥18 years old in a large private care setting between 01/01/1997 and 12/31/2009, comparing patients who missed visits in their first year following diagnosis (index period) with those who did not. Patients who died during the index period were excluded. Hazard ratios (HR) for association of missed visits and mortality were obtained by Cox proportional hazards regression, adjusting for patient demographics, CD4+ counts, and AIDS-defining conditions (CDC, 1993) at diagnosis. We also evaluated risk factors of missed visits by multivariable logistic regression. 2811 patients were included, of whom 65% had ≥1 missed visit, and 226 patients died during follow-up. Patients with ≥1 missed visit had a 71% increased mortality risk (HR=1.71, p=0.001) with 12% increased rate per missed visit (HR=1.12, p<0.001). Factors associated with missed visits were younger age (OR=1.69 compared to 60+ years), Black and Latino race/ethnicity (OR=1.54, 1.48 respectively, compared to Caucasians), injection drug use (OR=2.50 compared to men who have sex with men), and lower CD4+ (OR=1.43 for CD4+ 100-199 cells/µL, OR=1.39 for 50-99 cells/µL, and OR=1.63 for CD4+ <50 cells/µL, compared with CD4+ >500 cells/µL). In an insured patient population, missed visits in the first year of HIV care are common and associated with increased mortality. Early retention in HIV care is critical to improving outcomes.

The effect of HIV infection, immunodeficiency, and antiretroviral therapy on the risk of hepatic dysfunction.

BACKGROUND: Limited data exists regarding the effect of chronic HIV infection on the liver. We sought to characterize the hepatic risks of HIV infection, immunodeficiency, and cumulative use of antiretroviral therapy (ART). METHODS: Adult HIV infected and 10:1 age-matched and sex-matched HIV-uninfected individuals were followed for incident hepatic dysfunction or hepatic dysfunction-related death. Multivariable Poisson regression models were used to obtain incident rate ratios, adjusting for multiple hepatic risk factors including alcohol/drug abuse, hepatitis B and C, and diabetes. RESULTS: We identified 20,775 HIV-infected and 215,158 HIV-uninfected individuals. HIV-infected individuals had a significantly greater overall risk compared with HIV-uninfected individuals of both hepatic dysfunction and hepatic dysfunction-related death. The highest risk was seen in patients with low CD4 cell counts not on ART [adjusted rate ratio of hepatic dysfunction-related death 59.4; (95% confidence interval: 39.3 to 89.7), P < 0.001; hepatic dysfunction, adjusted rate ratio 15.7 (95% confidence interval: 11.4 to 21.6), P < 0.001]. In an HIV-infected only model, factors that increased risk included low CD4 cell count, high HIV RNA level, alcohol/drug abuse, hepatitis B or C coinfection, and diabetes. Longer cumulative exposure to ART did not increase risk, regardless of therapy class. CONCLUSIONS: HIV-infected individuals have a higher risk of hepatic dysfunction and hepatic dysfunction-related death compared with HIV-uninfected individuals, even with adjustment for known hepatic risk factors. Hepatic outcomes were associated with lower CD4+ T-cell counts but not with longer cumulative ART exposure. These findings provide indirect evidence supporting early use of ART to reduce the risk for hepatic-related complications.