To examine changes in use of prescription opioids for the management of chronic non-cancer pain in HIV-infected patients and to identify patient characteristics associated with long-term use.
Long-term prescription opioid use (i.e. 120+ days supply or 10+ prescriptions during a year) was assessed between 1997 and 2005 among 6,939 HIV-infected Kaiser Permanente members and HIV-uninfected persons in the general health plan memberships.
In 2005, 8% of HIV+ individuals had prevalent long-term opioid use, more than double the prevalence among HIV-uninfected individuals. However, the large increases in use from 1997 to 2005 in the general population were not observed for HIV-infected individuals. The strongest associations with prevalent use among HIV-infected individuals were female gender with a prevalence ratio [PR] of 1.8 (95% CI=1.3, 2.5); Charlson comorbidity score of 2 or more (compared with a score of 0) with a PR of 1.9 (95% CI=1.4, 2.8); injection drug use history with a PR of 1.8 (95% CI=1.3, 2.6); substance use disorders with a PR of 1.8 (95% CI=1.3, 2.5). CD4, HIV RNA, and AIDS diagnoses were associated with prevalent opioid use early in the antiretroviral therapy era (1997), but not in 2005.
Long-term opioid use for chronic pain has remained stable over time for HIV patients, while use increased in the general population. The prevalence of prescribed opioids in HIV patients was highest for certain subgroups, including women, and those with a comorbidity and substance abuse history.
HIV/AIDS; chronic pain; prescription opioids; substance use disorders
Few studies have compared cancer risk between HIV-infected individuals and a demographically-similar HIV-uninfected internal comparison group, adjusting for cancer risk factors.
We followed 20,775 HIV-infected and 215,158 HIV-uninfected individuals enrolled in Kaiser Permanente (KP) California for incident cancer from 1996–2008. Rate ratios (RR) were obtained from Poisson models comparing HIV-infected (overall and stratified by recent CD4 count and HIV RNA) with HIV-uninfected individuals, adjusted for age, sex, race/ethnicity, calendar period, KP region, smoking, alcohol/drug abuse, and overweight/obesity.
We observed elevated RRs for Kaposi sarcoma (KS) (RR=199; P<0.001), non-Hodgkin lymphoma (NHL) (RR=15; P<0.001), anal cancer (RR=55; P<0.001), Hodgkin lymphoma (HL) (RR=19; P<0.001), melanoma (RR=1.8; P=0.001), and liver cancer (RR=1.8; P=0.013), a reduced RR for prostate cancer (RR=0.8; P=0.012), and no increased risk for oral cavity/pharynx (RR=1.4; P=0.14), lung (RR=1.2; P=0.15), or colorectal (RR=0.9; P=0.34) cancers. Lung and oral cavity/pharynx cancers were elevated for HIV-infected subjects in models adjusted only for demographics. KS, NHL, anal cancer, HL, and colorectal cancer had significant (P<0.05) trends for increasing RRs with decreasing recent CD4. The RRs for lung and oral cavity/pharynx cancer were significantly elevated with CD4 <200 cells/µL and for melanoma and liver cancer with CD4 <500 cells/µL. Only KS and NHL were associated with HIV RNA.
Immunodeficiency was positively associated with all cancers examined except prostate cancer among HIV-infected compared with HIV-uninfected individuals, after adjustment for several cancer risk factors.
Earlier antiretroviral therapy initiation to maintain high CD4 levels might reduce the burden of cancer in this population.
HIV/AIDS; cancer; immunodeficiency; viral replication; epidemiology
Background and aim
Early in the combination antiretroviral therapy (cART) era, provider experience (as measured by panel size) was associated with improved outcomes. We explored that association and other characteristics of provider experience.
We performed a retrospective cohort analysis in Kaiser Permanente California (an integrated health care system in the United States), examining all human immunodeficiency virus seropositive (HIV+) patients initiating a first cART regimen (antiretroviral therapy [ART]-naïve, N = 7071) or initiating a second or later cART regimen (ART-experienced, N = 3730) from 1996–2006. We measured ART adherence through 12 months (pharmacy fill and refill records) and determined HIV viral load levels below limits of quantification at 12 months. Provider experience, updated annually, was measured as (1) HIV panel size (0–10 patients as reference strata), (2) years treating HIV (less than 1 year as reference), and (3) specialty ( noninfectious disease specialty, non-HIV expert as reference). We assessed associations by utilizing mixed modeling analyses (clustered by provider and medical center), controlling for patient age, sex, race/ethnicity, HIV risk behavior, hepatitis C coinfection, ART regimen class, and calendar year.
Among the ART-experienced, improved adherence was associated with greater years experience (mean increase 3.1% 2–5 years experience; 3.7% 5–10 years; 2.7% 11–20 years; P = 0.07, categorical). In adjusted analyses, viral suppression among ART-naïve was positively associated with panel size (odds ratio 26–50 patients: 1.31, P = 0.03, categorical), but negatively associated with years experience (18% less for greater than 100 patients; P = 0.003). No provider characteristic was significantly associated with improved adherence among ART-naïve or odds of maximal viral suppression among ART-experienced in adjusted analysis.
Except for panel size and years experience among ART-naïve, provider characteristics did not significantly influence ART adherence or likelihood of viral suppression.
antiretroviral therapy; adherence; provider-level factors; HIV-related outcomes
To report trends and characteristics of long-term opioid use for non-cancer pain.
CONSORT (CONsortium to Study Opioid Risks and Trends) includes adult enrollees of two health plans serving over one-percent of the US population. Using automated data, we constructed episodes of opioid use between 1997 and 2005. We estimated age-sex standardized rates of opioid use episodes beginning in each year (incident) and on-going in each year (prevalent), and the percent change in rates annualized (PCA) over the 9 year period. Long-term episodes were defined as > 90 days with 120+ days supply or 10+ opioid prescriptions in a given year.
Over the study period, incident long-term use increased from 8.5 to 12.1 per 1,000 at Group Health (GH) (6.0% PCA), and 6.3 to 8.6 per 1,000 at Kaiser Permanente of Northern California (KPNC) (5.5% PCA). Prevalent long-term use doubled from 23.9 to 46.8 per 1,000 at GH (8.5% PCA), and 21.5 to 39.2 per 1,000 at KPNC (8.1% PCA). Non-Schedule II opioids were the most commonly used opioid among patients engaged in long-term opioid therapy, particularly at KPNC. Long-term use of Schedule II opioids also increased substantially at both health plans. Among prevalent long-term users in 2005, 28.6% at GH and 30.2% at KPNC were also regular users of sedative hypnotics.
Long-term opioid therapy for non-cancer pain is increasingly prevalent, but the benefits and risks associated with such therapy are inadequately understood. Concurrent use of opioids and sedative-hypnotics was unexpectedly common and deserves further study.
pain; opioids; trends; analgesic
Prior studies evaluating racial/ethnic differences in responses to antiretroviral therapy (ART) among HIV-infected patients have not adequately accounted for many potential confounders, and few have included Hispanic patients.
To identify racial/ethnic differences in ART adherence, and risk of AIDS and death after ART initiation for HIV patients with similar access to care.
Retrospective cohort study.
4,686 HIV-infected patients (66% White, 20% Black, and 14% Hispanic) initiating ART and who were enrolled in an integrated healthcare system.
Main outcomes evaluated were ART adherence, new AIDS clinical events, and all-cause mortality. The potential confounding effects of demographics, socioeconomic status, ART parameters, HIV disease stage, and other clinical parameters were considered in multivariable models.
Adjusted mean adherence levels were higher among White (70.1%; ref) compared with Black (64.2%; < 0.001) and Hispanic patients (65.2%; < 0.001). Adjusted hazard ratios (HR) for the risk of new AIDS events (White patients as reference) were 1.3 ( = 0.09) for Black and 0.9 ( = 0.64) for Hispanic patients. The adjusted HR for AIDS comparing Hispanic to Black patients was 0.7 ( = 0.11). Hispanic patients had fewer deaths compared with other racial/ethnic groups, particularly cancer and cardiovascular-related. However, adjusted HRs for death were 1.2 ( = 0.37) and 0.9 ( = 0.62) for Black and Hispanic patients, respectively, compared with White patients and 0.9 ( = 0.63) for Hispanic compared with Black patients. Adjustment for adherence did not change inferences for AIDS or death.
In the setting of similar access to care, we did not observe a disparity for the risk of clinical events for racial/ethnic minorities, despite lower ART adherence.
race; ethnicity; AIDS; survival
Purpose of review
There is an increasing burden of non-AIDS-defining malignancies (NADM) in the antiretroviral therapy (ART) era. The recent literature is reviewed with respect to NADM risk, ART use, and immune function.
Recent studies have increasingly focused on individual ART use, CD4 T-cell counts and the risk of NADMs. Certain NADMs have been shown to have a reduced risk with ART use including liver, breast, colorectal, and lung cancers. NADMs associated with immunosuppression included Hodgkin’s lymphoma, oral/pharynx, lung, anal, and colorectal cancers. Despite the potential protective effect of ART on some NADMs, recent studies evaluating calendar era trends have noted an increased risk of Hodgkin’s lymphoma and anal cancer, and no change in risk for lung cancer in the ART era.
Successful ART use and improvements in immune function for HIV-infected persons may reduce the risk of certain NADMs. However, a continued high risk in the ART era for certain cancers have been observed, including Hodgkin’s lymphoma and anal cancers. Future studies should monitor trends in NADMs in HIV-infected persons in the ART era, as well as changes in the prevalence of risk factors, co-infections, and screening practices in this population.
HIV; antiretroviral therapy; immunodeficiency; malignancy
To determine the impact of age and initial HAART regimen class on virologic and immunologic response within 24 months after initiation.
Pooled analysis of data from 19 prospective cohort studies in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
Twelve thousand, one hundred and ninety-six antiretroviral-naive adults who initiated HAART between 1998 and 2008 using a boosted protease inhibitor-based regimen or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen were included in our study. Discrete time-to-event models estimated adjusted hazard odds ratios (aHOR) and 95% confidence intervals (CIs) for suppressed viral load (≤500 copies/ml) and, separately, at least 100 cells/μl increase in CD4 cell count. Truncated, stabilized inverse probability weights accounted for selection biases from discontinuation of initial regimen class.
Among 12 196 eligible participants (mean age = 42 years), 50% changed regimen classes after initiation (57 and 48% of whom initiated protease inhibitor and NNRTI-based regimens, respectively). Mean CD4 cell count at initiation was similar by age. Virologic response to treatment was less likely in those initiating using a boosted protease inhibitor [aHOR = 0.77 (0.73, 0.82)], regardless of age. Immunologic response decreased with increasing age [18–<30: ref; 30–<40: aHOR 0.92 (0.85, 1.00); 40–<50: aHOR = 0.85 (0.78, 0.92); 50–<60: aHOR = 0.82 (0.74, 0.90); ≥60: aHOR=0.74 (0.65, 0.85)], regardless of initial regimen.
We found no evidence of an interaction between age and initial anti-retroviral regimen on virologic or immunologic response to HAART; however, decreased immunologic response with increasing age may have implications for age-specific when-to-start guidelines.
age; CD4 lymphocyte count; HAART; HIV; viral load
The extended use of antiretroviral drugs among human immunodeficiency virus (HIV)–seropositive individuals underscores the need for a comprehensive evaluation of therapy-associated clinical symptoms.
Beginning in April 2000, 364 HIV-seronegative and 1256 HIV-seropositive women enrolled in a multicenter cohort study reported clinical symptoms that included abdominal pain, diarrhea, anorexia, nausea and/or vomiting, myalgias, fatigue, fever, body fat redistribution, dizziness, headaches, paresthesias, xerostomia, nephrolithiasis, and rash. We examined the prevalence of symptoms with respect to HIV infection and the use of highly active antiretroviral therapy (HAART), using data-correlation models.
In the 6 months before a study visit, 49% of HIV-seronegative women, 67% of HIV-seropositive women not receiving therapy, and 69% of HIV-seropositive women receiving HAART reported any clinical symptom. The odds ratios (ORs) for reporting any symptom were 1.4 (95% confidence interval [CI], 1.1–1.8) for women who changed HAART regimens and 0.9 (95% CI, 0.7–1.1) for women reporting stable HAART use, compared with those reporting no therapy use. Significant findings (P < .05) for particular symptoms were an increased odds of diarrhea, nausea and/or vomiting, body fat redistribution, myalgias, and paresthesias, when data for women who changed HAART regimens were compared with those for women not receiving therapy. The OR for reporting any symptom was 1.5 (95% CI, 1.2–1.9) for women who switched HAART regimens and 1.6 (95% CI, 1.3–1.9) for women who discontinued HAART, compared with those reporting stable HAART use.
Our findings confirm the high prevalence of clinical symptoms among HIV-seropositive women who changed HAART regimens. The high prevalence of symptoms among HIV-seronegative women and HIV-seropositive women not receiving therapy demonstrates that caution should be used when attributing the occurrence of symptoms entirely to HAART.
To determine if the concomitant use of nelfinavir (NFV) and proton pump inhibitors (PPIs) among HIV-positive individuals results in the loss of virologic control.
Kaiser Permanente Northern California (KPNC).
A total of 1,147 HIV-positive adults initiating NFV between November 1998 and June 2003 were included. The earlier date corresponds to the availability of the branched-DNA HIV viral load assay at KPNC and the later date corresponds to over-the-counter availability of PPIs.
Measurements and Main Results
The effect on two virologic outcomes, achieving undetectable HIV viral load and subsequent virologic rebound, were compared between subjects receiving NFV alone and NFV with PPIs. Cox proportional hazard models were utilized with adjustment for age, sex, race, HIV risk factors, hepatitis B or C co-infection, and other concurrent medications known to affect the metabolism of NFV. The use of PPIs had little effect on the ability to achieve an undetectable HIV viral load (adjusted hazard ratio (HR) = 0.82; 95% confidence interval (95% CI) = 0.58, 1.19; p = 0.29), but there was an approximate 50% increased risk of virologic rebound with the use of PPIs (adjusted HR = 1.53; 95% CI = 1.06, 2.19; p = 0.02). Short-term use of PPIs (defined as within 30 days of initial PPI dispensation) was not associated with increased risk of virologic rebound (HR = 1.07; 95% CI = 0.26, 4.41; p = 0.93) in comparison to no use.
Use of PPIs should be minimized or avoided in individuals who have attained an undetectable HIV viral load on a NFV-based antiretroviral regimen. However, concomitant use of these medications may be acceptable for indications where PPIs are required for < 30 days.
nelfinavir; proton pump inhibitors; omeprazole; interaction; HIV; virologic rebound
Chronic opioid therapy for chronic non-cancer pain (CNCP) is increasingly common in community practice. Concomitant with this practice change, rates of fatal opioid overdose have increased. It is not known to what extent overdose risks are elevated among patients receiving medically prescribed chronic opioid therapy.
To estimate rates of opioid overdose and their association with average prescribed daily opioid dose among patients receiving medically prescribed chronic opioid therapy.
Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at time of overdose.
Health maintenance organization.
Individuals (n=9940) who received 3+ opioid prescriptions within 90-days for CNCP between 1997 and 2005.
Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes, non-fatal and fatal overdoses, were identified through diagnostic codes from inpatient and outpatient care and death certificates and confirmed by medical record review.
Fifty-one opioid-related overdoses were identified, including six deaths. Compared to patients receiving 1-20mg of opioids per day (0.2% annual overdose rate), patients receiving 50-99 mg had a 3.7 fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7% annual overdose rate. Patients receiving 100mg or more per day had an 8.9 fold increase in overdose risk (95% C.I. 4.0, 19.7) and a 1.8% annual overdose rate.
Increased overdose risk among patients on higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation.
Patients receiving higher doses of prescribed opioids are at increased risk of opioid overdose, underscoring the need for close supervision of these patients.
To evaluate the risk of cancers with and without a known infectious cause in HIV-infected persons.
Retrospective cohort study.
Adult HIV-infected and matched HIV-uninfected members of Kaiser Permanente followed between 1996 and 2007 for incident AIDS-defining cancers (ADC), infection-related non-AIDS-defining cancers (NADC) (anal squamous cell, vagina/vulva, Hodgkin’s lymphoma, penis, liver, HPV-related oral cavity/pharynx, stomach) and infection-unrelated NADC (all other NADC).
We identified 20,277 HIV-infected and 202,313 HIV-uninfected persons. HIV-infected persons experienced 552 ADC, 221 infection-related NADC, and 388 infection-unrelated NADC. HIV-uninfected persons experienced 179 ADC, 284 infection-related NADC, and 3,418 infection-unrelated NADC. The rate ratio (RR) comparing HIV-infected and HIV-uninfected persons for ADC was 37.7 (95% CI: 31.7–44.8), with decreases in the RR over time (p<0.001). The RR for infection-related NADC was 9.2 (95% CI: 7.7–11.1), also with decreases in the RR over time (p<0.001). These results were largely influenced by anal squamous cell cancer and Hodgkin’s lymphoma. The RR for infection-unrelated NADC was 1.3 (95% CI: 1.2–1.4), with no change in the RR over time (p=0.44). Among infection-unrelated NADC, other anal, skin, other head and neck, and lung cancer rates were higher and prostate cancer rates lower in HIV-infected persons. Among all infection-unrelated NADC, the RR decreased over time only for lung cancer (p=0.007).
HIV-infected persons are at particular risk for cancers with a known infectious cause, although the higher risk has decreased in the antiretroviral therapy era. Cancers without a known infectious cause are modestly increased in HIV-infected persons.
HIV; cancer; incidence; coinfection; cohort
We report trends in long-term opioid use among patients from two large health plans with a history of depression.
Using claims data, age and gender-adjusted rates for long-term (>90 days) opioid use episodes were calculated for 1997–2005, comparing those with and without a depression diagnosis in the prior two years. Opioid use characteristics were calculated for those with a long-term episode in 2005.
Incident and prevalent long-term opioid use rates were three times higher in those with a history of depression. Prevalent long-term use per 1,000 in patients with a history of depression increased from 69.8 to 125.9 at Group Health, and from 84.3 to 117.5 at Kaiser Permanente of Northern California between 1997 and 2005. Those with a history of depression were more likely to receive a higher average daily dose, greater days supply, and Schedule II opioids than non-depressed persons.
Persons with a history of depression are more likely to receive long-term opioid therapy for non-cancer pain than those without a history of depression. Results suggest that long-term opioid therapy for non-cancer pain is being prescribed to a different population in clinical practice than the clinical trial populations where opioid efficacy has been established.
opioid; pain; depression; pharmacoepidemiology
Long-term opioid therapy for non-cancer pain has increased. Caution is advised in prescribing for persons with substance use disorders, but little is known about actual health plan practices. This paper reports trends and characteristics of long-term opioid use in persons with non-cancer pain and a substance abuse history. Using health plan data (1997–2005), the study compared age–sex-standardized rates of incident, incident long-term and prevalent long-term prescription opioid use, and medication use profiles in those with and without substance use disorder histories. The CONsortium to Study Opioid Risks and Trends study included adult enrollees of two health plans, Kaiser Permanente of Northern California (KPNC) and Group Health Cooperative (GH) of Seattle, Washington. At KPNC (1999–2005), prevalence of long-term use increased from 11.6% to 17.0% for those with substance use disorder histories and from 2.6% to 3.9% for those without substance use disorder histories. Respective GH rates (1997–2005), increased from 7.6% to 18.6% and from 2.7% to 4.2%. Among persons with an opioid disorder, KPNC rates increased from 44.1% to 51.1%, and GH rates increased from 15.7% to 52.4%. Long-term opioid users with a prior substance abuse diagnosis received higher dosage levels, were more likely to use Schedule II and long-acting opioids, and were more often frequent users of sedative-hypnotic medications in addition to their opioid use. Since these patients are viewed as higher risk, the increased use of long-term opioid therapy suggests the importance of improved understanding of the benefits and risks of opioid therapy among persons with a history of substance abuse, and the need for more careful screening for substance abuse history than is the usual practice.
Prescription opioid episodes; Substance use disorders; Chronic pain management in managed care
Few studies have evaluated age and racial/ethnic differences in the prevalence of symptoms in HIV infection. Thus, the objective of this study was to compare the prevalence of gastrointestinal, metabolic, general malaise, neurologic, or other self-reported symptoms by age and race/ethnicity among 1,574 HIV-infected women enrolled in the Women’s Interagency HIV Study and 955 HIV-infected men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study. All patients had known dates of initiation of highly-active antiretroviral therapy. It was observed that women ≥50 years were less likely to experience gastrointestinal symptoms (24% vs. 27%, multivariable p=0.024), but more likely to experience general malaise (47% vs. 37%; multivariable p=0.004), neurologic (44% vs. 38%; multivariable p=0.048), or other symptoms (40% vs. 28%; multivariable P<0.001) compared to women <40 years of age. Only neurologic symptoms had a higher prevalence among older MSM (52% vs. 37%; multivariable P=0.002), largely driven by paresthesias (48% vs. 31%; multivariable p=0.004), the most common individual symptom reported by men. Caucasian women generally had the highest prevalence of symptoms and African-American women had the lowest prevalence. Few racial/ethnic differences were noted for MSM. Depression and a prior diagnosis of AIDS were the strongest and most consistent predictors of clinical symptoms in both cohorts. In summary, the prevalence of reported symptoms varies with patient race/ethnicity, age, and modifiable factors such as depression and HIV disease stage. Clinicians should consider these factors when counseling patients regarding potential adverse effects of antiretrovirals or symptoms associated with HIV disease.
Highly active antiretroviral therapy; symptoms; gender; race/ethnicity; aging
Background. Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts.
Methods. Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995–August 2009. Parametric survival models identified factors associated with tuberculosis occurrence.
Results. Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131–333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk.
Conclusions. Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm3 or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.
Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs.
Smoking/tobacco; Genital warts; Human papillomavirus (HPV); HIV; men who have sex with men (MSM); CD4+ T-lymphocyte count; longitudinal/cohort
Serial measurement of antibodies has not been used to provide evidence of active viral replication of human papillomavirus (HPV). Serum specimens from sequential study visits contributed by 642 human immunodeficiency virus (HIV)-positive and 116 HIV-negative participants enrolled in the Women's Interagency HIV Study were used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors associated with a significant rise were identified using multivariable logistic regression models with generalized estimating equations. Among HIV-positive women, 8.3% of 1,997 pairs showed antibody rises, compared to 6.1% of 361 pairs among HIV-negative women (P = 0.191). For HIV-positive women, rises were associated with current (odds ratio [OR], 23.4; P < 0.001) or past (OR, 8.9; P < 0.001) HPV-16 infection relative to never being HPV-16 infected and with CD4+ cell counts (OR per 100-cell increase, 0.8; P < 0.001) but not with sexual behavior. For HIV-negative women, rises were associated with past (OR, 10.9; P = 0.033) HPV-16 infection relative to no HPV-16, current cigarette smoking (OR, 5.0; P = 0.029) relative to no smoking history, and having 6 to 10 lifetime sexual partners compared to 0 to 5 partners (OR, 9.9; P = 0.036). Serial measurement of HPV-16 serum antibodies is a useful tool for identifying active HPV-16 viral replication. Rises among HIV-positive women may more often result from reactivation of a latent HPV infection in the context of HIV-induced immunosuppression, while rises among HIV-negative women may more often result from reinfection with HPV.
Initiatives to improve early detection and access to HIV services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997-2007 in 13 US and Canadian clinical cohorts.
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) measurement 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/mm3) and 95% confidence intervals ([,]) were determined using linear regression adjusted for age, gender, race/ethnicity, HIV transmission risk and cohort.
Median age at first presentation for HIV care increased over time (range 40-43 years, p<0.01), while the proportion of patients with injection drug use HIV transmission risk decreased (26% to 14%, p<0.01) and heterosexual transmission risk increased (16% to 23%, p<0.01). Median CD4 at presentation increased from 256 (IQR: 96-455) to 317 (IQR: 135-517) in 1997 to 2007 (p<0.01). The proportion with a CD4 count ≥350 at first presentation also increased from 1997 to 2007 (38% to 46%, p=<0.01). The estimated adjusted mean CD4 count increased at a rate of 6 [5, 7] per year.
CD4 count at first presentation for HIV care has increased annually over the past 11 years, but has remained <350 cells/mm3, suggesting the urgent need for earlier HIV diagnosis and treatment.
CD4 Lymphocyte Count; Delivery of Health Care / statistics & numerical data; HIV Infections / therapy; United States; Canada
We describe age and gender trends in long-term use of prescribed opioids for chronic noncancer pain in 2 large health plans.
Age- and gender-standardized incident (beginning in each year) and prevalent (ongoing) opioid use episodes were estimated with automated health care data from 1997 to 2005. Profiles of opioid use in 2005 by age and gender were also compared.
From 1997 to 2005, age–gender groups exhibited a total percentage increase ranging from 16% to 87% for incident long-term opioid use and from 61% to 135% for prevalent long-term opioid use. Women had higher opioid use than did men. Older women had the highest prevalence of long-term opioid use (8%–9% in 2005). Concurrent use of sedative-hypnotic drugs and opioids was common, particularly among women.
Risks and benefits of long-term opioid use are poorly understood, particularly among older adults. Increased surveillance of the safety of long-term opioid use is needed in community practice settings.
We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in 13 US and Canadian clinical cohorts and compared to <50-year-olds. 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included in our study. Trends in mean CD4 count (measured as cells/mm3) and 95% confidence intervals ([,]) were determined using linear regression stratified by age category and adjusted for gender, race/ethnicity, HIV transmission risk and cohort. From 1997-2007, the proportion of individuals presenting for HIV care who were ≥50-years-old increased from 17% to 27% (p-value < 0.01). The median CD4 count among ≥50 year-olds was consistently lower than younger adults. The interaction of age group and calendar year was significant (p-value <0.01) with both age groups experiencing modest annual improvements over time (< 50-year-olds: 5
[4 , 6] cells/mm3; ≥50-year-olds: 7
[5 , 9] cells/mm3), after adjusting for sex, race/ethnicity, HIV transmission risk group and cohort; however, increases in the two groups were similar after 2000. A greater proportion of older individuals had an AIDS-defining diagnosis at, or within three months prior to, first presentation for HIV care compared to younger individuals (13% vs. 10%, respectively). Due to the increasing proportion, consistently lower CD4 counts, and more advanced HIV disease in adults ≥50-year-old at first presentation for HIV care, renewed HIV testing efforts are needed.
Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined.
Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure.
Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4+ T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients
Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4+ T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.
The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.
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).
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).
The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.