INSOMNIA SYMPTOMS AND HIV INFECTION IN WOMEN http://dx.doi.org/10.5665/sleep.1602
Insomnia Symptoms and HIV Infection among Participants in the Women’s Interagency HIV Study
Girardin Jean-Louis, PhD1,2; Kathleen M. Weber, RN3; Bradley E. Aouizerat, PhD4; Alexandra M. Levine, MD5; Pauline M. Maki, PhD6; Chenglong Liu, MD7; Kathryn M. Anastos, MD8; Joel Milam, PhD9; Keri N. Althoff, PhD10; Tracey E. Wilson, PhD11 1 Sleep Disorders Center, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY; 2Brooklyn Health Disparities Center, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY; 3The CORE Center at John H. Stroger Jr. Hospital of Cook County & Hektoen Institute of Medicine, Chicago, IL; 4University of California, San Francisco, San Francisco, CA; 5Department of Medicine, University of Southern California, Los Angeles, CA; 6Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, IL; 7Department of Medicine, Georgetown University, Washington, DC; 8Department of Epidemiology, Montefiore Medical Center, Bronx, NY; 9Keck School of Medicine, University of Southern California, Los Angeles, CA; 10Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; 11Department of Community Health Sciences, SUNY Downstate Medical Center, Brooklyn, NY
Objectives: This study assessed the prevalence of insomnia symptoms among women with and without HIV-infection and examined factors associated with insomnia. Design: Participants (n = 1682) were enrolled in the Women’s Interagency HIV Study (WIHS); 69% were infected with HIV. This was a crosssectional analysis of data from standardized interviewer-administered instruments and physical/gynecological exams. Analysis focused on sociodemographics, sleep measures, depressive symptoms, drug use, alcohol consumption, medications, and HIV-related clinical variables. Women were classified as having symptoms of insomnia if they reported either difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening ≥ 3 times a week in the past 2 weeks. Results: Overall, HIV-infected women were 17% more likely to endorse insomnia symptoms than uninfected women (OR = 1.17, 95% CI: 1.041.34, P < 0.05). The adjusted prevalence of insomnia symptoms varied by HIV status and age groups. Among women ages 31-40 years, those with HIV infection were 26% more likely to endorse insomnia symptoms than their counterparts (OR = 1.26, 95% CI: 1.01-1.59, P < 0.05). No significant differences were observed in the likelihood of reporting insomnia symptoms based on HIV treatment type. Multivariate-adjusted regression analyses showed that depression was the most consistent and significant independent predictor of the likelihood of reporting insomnia symptoms across all age strata. Conclusions: Insomnia symptoms are common among both HIV-infected and uninfected women. Prevalence of insomnia did not vary significantly by HIV status, except among younger women. Younger women with HIV infection are at greater risk for experiencing insomnia symptoms. Keywords: Insomnia, sleep, women, HIV infection Citation: Jean-Louis G; Weber KM; Aouizerat BE; Levine AM; Maki PM; Liu C; Anastos KM; Milam J; Althoff KN; Wilson TE. Insomnia symptoms and HIV infection among participants in the Women’s Interagency HIV Study. SLEEP 2012;35(1):131-137.
INTRODUCTION Insomnia symptoms increase with age and are common among individuals with chronic diseases.1-5 It is estimated that 73% of HIV-infected adults report insomnia symptoms, defined as reporting difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening.6 Insomnia symptoms have been associated with fatigue, excessive daytime sleepiness, depressed moods, cognitive and neurobehavioral dysfunctions, and diminished quality of life in HIV-infected adults.5,7-11 This is a special concern to clinicians who treat HIV-infected patients, as insomnia is reported through all stages of the disease.6,7,12,13 Furthermore, patients complaining of insomnia tend to show poor adherence to recommended treatment,8 which further complicates clinical management. Despite the potentially devastating effects of insomnia among patients with HIV infection, little has been done
Submitted for publication September, 2010 Submitted in final revised form May, 2011 Accepted for publication July, 2011 Address correspondence to: Girardin Jean-Louis, PhD, SUNY Downstate Medical Center (Box 1199), 450 Clarkson Avenue, Brooklyn, NY 112032098; Tel: (718) 270-2716; Fax: (718) 270-2917; E-mail: gjean-louis@ downstate.edu SLEEP, Vol. 35, No. 1, 2012 131 Downloaded from https://academic.oup.com/sleep/article-abstract/35/1/131/2453859 by guest on 12 August 2018
to delineate systematically the factors that are associated with insomnia in this population.1,6 Emerging interest in the study of sleep patterns among individuals with HIV infection is fueled in part by evidence that certain antiretrovirals, such as efavirenz, might cause an increase in insomnia symptoms.14,15 Thus, although antiretroviral (ARV) regimens prolong survival rates,16 there is a concern that certain drugs in the regimens might worsen daytime functioning due to increased risk for insomnia.12 It is unclear whether ARV exacerbates existing sleep problems or induces them in at-risk patients. Previous research on insomnia in the context of HIV infection has been limited by lack of power and/or inadequate control groups.1 Moreover, only a handful of clinical studies have examined the associations between ARV regimens and sleep measures among HIV-infected individuals. The objective of this study was to determine the prevalence of, and riskfactors for, insomnia symptoms in HIV-infected and similar, uninfected women. In a sub-analysis of HIV-infected women, the association of ARV regimen and the prevalence of insomnia symptoms was examined. These aims capitalize on the strengths of the WIHS as a prospective cohort study collecting protocol-driven data outside of clinical care from women who reflect the epidemiologic characteristics of HIV infection in women in the US. Insomnia Symptoms and HIV Infection—Jean-Louis et al
METHODS Participants Data for the present cross-sectional analysis were obtained from women participating in the WIHS. WIHS is a multisite prospective cohort study of HIV-infected women in the United States. Since its establishment in 1994, WIHS has been a comprehensive research program focusing on the impact of HIV infection among women. Women enrolled in the studies are seen during semiannual study visits at participating sites in Brooklyn and Bronx, New York; Washington, DC; Los Angeles and San Francisco, California; and Chicago, Illinois. These women were originally recruited from several venues, which include hospital-based programs, HIV primary care clinics, community outreach sites, research programs, support groups, HIV testing and drug rehabilitation programs, and referrals from enrolled participants. Details on the WIHS recruitment methods have been published previously17; additional information can be obtained from the WIHS Website (https://statepiaps.jhsph.edu/wihs/). Procedures Women participating in the WIHS routinely undergo semiannual physical and gynecological examinations, complete standardized questionnaires, and provide blood samples for measurement of biomarkers. Subjective and clinical measures used for the present analysis were collected during scheduled study visits occurring in 2006 at all participating sites. Questionnaire data were obtained during quality-controlled, standardized face-to-face interviews. All interviewers received extensive training on all items collected during the interviews and were sensitized to the need to minimize social desirability bias while addressing sensitive issues. All women participating in the study provide informed written consent under the supervision of institutional review boards at each study site. Physical examinations yielded data on lipoatrophy symptoms, body mass index (kg/m2), and diabetes status; diabetes was classified as a current or prior measure of fasting glucose ≥ 126 mg/dL measured at 2 consecutive study visits, or selfreported diabetes mellitus or use of anti-diabetic medication. Women were also assessed for HIV RNA viral load. Plasma HIV-1 RNA quantification was performed using the isothermal nucleic acid sequence-based amplification method in laboratories, certified by the National Institutes of Health Virology Quality Assurance program, with a lower limit of detection set at 80 copies/mL. CD4 T-cell count and HIV-RNA viral load assessments were conducted at the same study visit corresponding to the interview conducted in 2006. Women with HIV infection provided additional data regarding medications for current medical conditions (i.e., seizures, diabetes, and heart disease) and depression as well as use of HIV antiretroviral therapy. All of these medications are associated with sleep problems, according to previous research.12,14,15,18-20 Antiretroviral therapy was categorized among HIV infected women as (1) not receiving antiretroviral therapy, (2) receiving non-HAART antiretroviral therapy, or (3) following a HAART regimen. The definition of HAART was guided by the DHHS/ Kaiser Panel (DHHS/Kaiser 2004) guidelines at the time of data collection and defined as: (a) ≥ 2 NRTIs in combination with at SLEEP, Vol. 35, No. 1, 2012 132 Downloaded from https://academic.oup.com/sleep/article-abstract/35/1/131/2453859 by guest on 12 August 2018
≥ 1 PI or 1 NNRTI; (b) 1 NRTI in combination with ≥ 1 PI and ≥ 1 NNRTI; (c) a regimen containing ritonavir and saquinavir in combination with 1 NRTI and no NNRTIs; and (d) an abacavir or tenofovir containing regimen of ≥ 3 NRTIs in the absence of both PIs and NNRTIs, except for the 3-NRTI regimens consisting of: abacavir + tenofovir + lamivudine or didanosine + tenofovir + lamivudine. Combinations of zidovudine (AZT) and stavudine (d4T) with either a PI or NNRTI were not considered HAART regimens. Insomnia symptoms were defined as a report of either difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening, ≥ 3 times/week in the previous 2 weeks. Although information regarding frequency and duration was obtained, no formal insomnia diagnosis could be formulated, as we did not elicit data on severity of insomnia symptoms or on associated daytime dysfunctions, two important parameters in rending an insomnia diagnosis based on practice guidelines established by the American Academy of Sleep Medicine.21 Symptoms of depression were assessed using the 20-item Center for Epidemiologic Studies Depression (CES-D) scale.22 A CES-D score > 23 was used to identify women with moderate to severe depression.23 Use of antidepressants was also recorded. Recent drug use included any use of marijuana, cocaine, crack, heroin, amphetamines or methamphetamine, hallucinogens, club drugs, or non-prescribed methadone or narcotics since the last study visit. Alcohol use since the last visit was defined as any consumption of wine, beer, hard liquor, or other alcoholic beverages. Menopausal status was defined by selfreported menstrual pattern; women who reported no menses for the past 12 months were classified as postmenopausal and others were defined as non-menopausal, as per WHO definitions and as used in previous research assessing menopausal status among women with HIV infection.24 Women who were currently pregnant or lactating or who reported ever having had a hysterectomy or oopherectomy were coded as “other” for this measure. All data were coded by an experienced data manager and were analyzed with SPSS 18.0. Statistical Analysis Eligible WIHS participants for this analysis included 1,682 women (1,117 HIV-infected and 506 uninfected women); controls included women who were at risk for HIV. Both groups provided complete data on sociodemographic, subjective, clinical status, as well as sleep questionnaires. Data analysis focused on the relationships between age-related insomnia symptoms and HIV infection, examining the contributory role of several sociodemographic, subjective, clinical, and medical explanatory factors. Frequency and measures of central tendency were used to describe the sample. ANOVA was used to analyze continuous data, and χ2 was used to analyze categorical data (e.g., personal, health risk, clinical, medical, and treatment measures). Since we expected that age would be a significant confounder in analysis assessing association between HIV status and insomnia symptoms, in preliminary analysis we performed univariate tests assessing associations between age and the insomnia symptom variable. For that purpose, the sample was age-stratified by decades: 20-30, 31-40, 41-50, 51-60, and 61-70; since only 12 respondents were between 71 and 80 years old, this stratum was excluded from further analyses. Thus, in order to test the Insomnia Symptoms and HIV Infection—Jean-Louis et al
Table 1—Sociodemographic characteristics of the sample (n = 1682) No HIV Infection
HIV Infection
26.4 ± 2.2 35.1 ± 2.8 44.9 ± 2.7 53.7 ± 2.4 64.5 ± 3.9
27.6 ± 1.9 13.6* 36.1 ± 2.7 13.2* 45.1 ± 2.9 0.39 53.6 ± 2.4 0.05 65.1 ± 4.1 0.22 16.8* 14.9 63.6 18.2 3.4 8.8* 21.5 13.3 65.2 65.8 1.14 37.6 2.1
9.3 61.7 24.5 4.5 23.5 8.1 68.4 64.8 40.5
100
F/χ2
Sociodemographic characteristics of the sample were compared using ANOVA and χ2 tests; 69% of participating women were infected with HIV and 31% were uninfected; *significant differences at α < 0.01.
hypothesis that the likelihood of reporting insomnia symptoms was greater for women who were HIV infected than those who were not, 5 age strata were considered. Since the prevalence of insomnia symptoms was > 10% in the overall sample, crude and adjusted prevalence ratios (PR and aPR, respectively) and 95% confidence intervals (95% CI) were estimated using Poisson approximations to log-binomial regression models with robust variance; this provided an asymptotically unbiased estimate of the prevalence ratio for insomnia symptoms.25 To assess the independent associations between the insomnia symptom variable and candidate predictors, logistic regression modeling was used. The dependent measure was insomnia symptom (coded as present or absent). Candidate predictors included sociodemographic factors: race/ethnicity, income, education, marital status, living with a partner, and employment status. Clinical factors were duration of HIV disease, CD4 count, viral load, lipoatrophy, menopausal status, and depression. Medical factors were obesity and presence of diabetes. Health risk factors were illicit drug use and alcohol consumption. Medications included antiretroviral therapy dummy-coded as (1) no antiretroviral therapy, (2) no-HAART antiretroviral therapy, or (3) HAART regimen, use of antidepressants, and other medications: i.e., heart disease, seizure, and diabetes. Only factors showing significant correlations (P < 0.05) with the dependent measure were entered in the final regression model; this helped to reduce redundancy in the model. Effects of all factors entered in the model were simultaneously adjusted. RESULTS Sociodemographic characteristics of participating women are provided in Table 1. Except for education and income, all sociodemographic factors showed differences between the 2 SLEEP, Vol. 35, No. 1, 2012 133 Downloaded from https://academic.oup.com/sleep/article-abstract/35/1/131/2453859 by guest on 12 August 2018
HIV+
Insomnia Symptoms, %
Variable Age (yrs), mean ± SD 20-30 31-40 41-50 51-60 61-70 Race/Ethnicity, % White Black Hispanic Other Marital status, % Married Divorced Single Education (≥ high school), % Annual Income (≥ $18,000), %
Insomnia Symptoms and HIV Infection Among WIHS Women HIV-
80 60 40 20 0
20-30
31-40
41-50
51-60
61-70
Age Strata Figure 1—Illustration of age-related associations with insomnia symptoms, contrasting women with HIV infection and uninfected women. The insomnia symptom variable represented an aggregate of women reporting either difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening, relative to those reporting no symptoms. Significant difference was noted for women ages 31-40 years.
groups: HIV infected and uninfected women. The likelihood of reporting insomnia symptoms was influenced by women’s ethnicity (white = 69%, Hispanic = 67%, black = 61%, and other = 64%; χ2 = 8.44, P < 0.001). Women reporting an annual income < $18,000 were more likely to indicate insomnia symptoms (68% vs. 56%; χ2 = 22.27, P < 0.001). Women’s education level did not significantly affect the likelihood of reporting insomnia symptoms (< high school = 65% vs. ≥ high school = 63%; χ2 = 0.71, NS), nor did their marital status (single = 64%, married = 63%, and divorced = 69%; χ2 = 2.27, NS). As depicted in Figure 1, the likelihood of reporting insomnia symptoms differed by HIV status and by age groups. Among women ages 20-30 years, no significant difference was found in the rate of insomnia symptoms (χ2 = 1.78, NS). Among women ages 31-40 years, rates were significantly higher among HIVinfected women (χ2 = 3.54, P < 0.05). Among women ages 41-50 years, no difference was found (χ2 = 0.01, NS). Among women ages 51-60 years, no significant difference was found (χ2 = 0.75, NS). Among women ages 61-70 years, no significant difference was found (χ2 = 0.26, NS). To estimate the overall prevalence of insomnia symptoms, we used GEE with a log-binomial regression model (Poisson approximations with robust variance). Results showed that overall HIV-infected women were 17% more likely to endorse insomnia symptoms than uninfected women (OR = 1.17, 95% CI: 1.04-1.34, P < 0.05). As shown in Table 2, the crude and adjusted prevalence of insomnia symptoms varied by HIV status and age groups. Estimates were significantly higher for women with HIV infection ages 31-40 years. Trends indicated greater estimates for women ages 20-30 years and for those ages 61-70 years; for HIV-infected women ages 51-60 years, trends suggested lower estimates of insomnia symptoms. Table 3 compares health risk, clinical, and medical measures obtained from HIV-infected women who reported insomnia Insomnia Symptoms and HIV Infection—Jean-Louis et al
Table 2—Prevalence of insomnia symptoms among women with HIV infection in the WIHS cohort Adjusted Prevalence Ratio & 95% CI 1.05 (0.74-1.09) 1.26 (1.01-1.59)* 1.02 (0.80-1.31) 0.75 (0.46-1.22) 1.02 (0.80-1.31)
Crude and adjusted prevalence estimates and 95% confidence intervals (95% CI) for the association between age and insomnia symptoms were obtained using a Poisson regression model with robust variance. Estimates were referenced to values obtained from uninfected women. The insomnia symptom variable aggregated women reporting either difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening vs. those who did not. Covariates included race/ethnicity, income, education, and marital status; *significant at α < 0.05.
Table 3—Factors associated with insomnia symptoms among women with HIV infection Variable Alcohol use Illicit drug use Obesity Depression Postmenopausal status Detectable viral load CD4 (< 500 cells/mL) Lipoatrophy Length of HIV infection (< 15 yrs) Medication usea Antidepressant use
Insomnia Insomnia No (%) Yes (%) 44.5 40.4 22.3 22.4 40.1 40.2 9.6 27.6 12.7 18.7 47.0 45.9 44.1 46.2 10.1 12.2 48.7 46.8 18.4 30.2 13.3 28.2
χ2 2.42 0.03 1.21 71.82* 10.13* 0.08 1.37 1.44 0.65 28.36* 46.32*
Comparison of health risk, clinical and medical characteristics of HIVinfected women reporting insomnia symptoms with those indicating no insomnia symptoms using χ2 tests. Length of HIV infection was split at the median. aMedication use included prescription for seizure, heart disease, and/or diabetes; *significant differences at α < 0.01.
symptoms vs. HIV-infected women who did not. Those reporting insomnia symptoms were more likely to be depressed, postmenopausal, and to have used antidepressants or medication for seizures, diabetes, and heart disease. No significant differences were observed in the likelihood of reporting insomnia symptoms based on HIV treatment regimens, but a greater proportion of women receiving non-HAART ARV therapy tended to report insomnia symptoms (Figure 2). A logistic regression model was constructed examining relationships of several hypothesized candidate predictors to insomnia within each age group. Of the factors considered in preliminary analyses, white and black ethnicity, income, postmenopausal status, depression, antidepressants, and use of seizure/diabetes/heart disease medications showed significant associations with the insomnia symptom variable (P < 0.05). SLEEP, Vol. 35, No. 1, 2012 134 Downloaded from https://academic.oup.com/sleep/article-abstract/35/1/131/2453859 by guest on 12 August 2018
90
Insomnia Symptoms, %
Age Strata 20-30 years (n = 155) 31-40 years (n = 431) 41-50 years (n = 654) 51-60 years (n = 325) 61-70 years (n = 58)
Crude Prevalence Ratio & 95% CI 1.16 (0.83-1.62) 1.23 (1.02-1.53)* 0.99 (0.78-1.26) 0.83 (0.53-1.29) 1.04 (0.33-3.22)
Insomnia Symptoms and HIV Treatment
80 70 60 50 40
No ARV
HAART
Non-HAART ARV
Figure 2—Depiction of estimated insomnia symptoms based on HIV treatment type: (1) no antiretroviral (ARV) therapy, (2) higly active antiretroviral therapy (HARRT), and (3) non-HAART ARV therapy.
Table 4—Association of depression with insomnia symptoms Age Strata 20-30 years 31-40 years 41-50 years 51-60 years 61-70 years
Odds Ratio & 95% CI 2.80 (1.06-7.39)* 3.50 (1.87-6.55)* 3.49 (2.09-5.81)* 2.14 (1.04-4.40)* 1.49 (0.24-9.16)
Regression coefficients of the insomnia symptom measure on sociodemographic and medical factors. Depression was the most consistent and significant predictor of insomnia symptoms across age strata; *significant at α < 0.01.
Hispanic ethnicity, HIV therapy type, duration of HIV infection, CD4 count, lipoatrophy, viral load, illicit drug use, and alcohol consumption were excluded from the model, as no significant correlations to insomnia symptoms were noted. As shown in Table 4, having symptoms indicative of depression was the most consistent and significant independent predictor of the likelihood of reporting insomnia symptoms across all age strata; effects of income, race/ethnicity, postmenopausal status, and medication use were adjusted. DISCUSSION A review of the literature on insomnia among individuals with HIV infection indicates that firm conclusions cannot be made, largely because of insufficient sample sizes, lack of adequate controls, and differing definitions for insomnia.1 In the present study, we estimated the prevalence of insomnia symptoms in a large, well-defined cohort of women with HIV infection and their HIV-uninfected counterparts and explored independent associations of sociodemographics, clinical factors, health risks, and HIV treatments with insomnia symptoms among women with HIV infection. The main finding of our analyses is that the adjusted prevalence estimate of insomnia symptoms was significantly higher for women with HIV infection ages 3140 years (see Table 2). Prevalence estimates for women in other age groups did not vary significantly by HIV status. Insomnia Symptoms and HIV Infection—Jean-Louis et al
The overall estimate of insomnia symptoms is consistent with previous estimates of sleep related complaints from epidemiologic and clinical studies. According to data from an HIV/AIDS clinic at an urban teaching hospital, 73% of participating outpatients showed evidence of sleep disturbance based on data derived from the Pittsburgh Sleep Quality Index scale.6 Similarly, data from another HIV clinic in a large Midwestern metropolitan area, suggested that 66% of HIV-infected individuals reported insomnia symptoms.26 The fact that estimates of insomnia symptoms among patients with HIV infection vary from 29%27 to 100%5 is attributable in part to the utilization of differing methodological and definitional criteria.1 Our cross-sectional analysis of WIHS data suggests that over 60% of women with HIV infection are likely to report insomnia symptoms, although age-related effects on prevalence estimates should be expected. Of note, our definition of insomnia symptoms is consistent with guidelines established by the American Academy of Sleep Medicine,21 ensuring the comparability of our findings with future estimates in that population. Greater prevalence of age-associated insomnia symptoms in both HIV-infected and uninfected women would have been predicted based on previous epidemiologic studies.28-31 The National Sleep Foundation estimates that two-thirds of American adults experience trouble sleeping during their lifetime.32 The finding that women with HIV infection below the age of 41 years were more likely to report insomnia symptoms is interesting. Multivariate analysis indicated that this observation was not affected by women’s race/ethnicity, income, education, or marital status. Our analysis did not identify specific factors likely to explain excess risk for insomnia symptoms among younger women, other than their HIV status. Previous research suggests that factors contributing to the likelihood of experiencing insomnia among younger women might include the presence of children in the household33 and pregnancy34; environmental factors (e.g., sleeping alone, having a separate bedroom, and sleeping in a noisy room) could also play a role.12 An alternative explanation could be that older women with HIV infection tend to experience less psychological burden associated with HIV disease,35 which is perhaps attributable to the acquisition of greater coping skills or psychological resources.36 Indeed, trends suggested lower prevalence of insomnia symptoms among women ages 51-70 years, relative to age-matched uninfected women (see Figure 1). The suggestion that reduced HIV-related psychological burden observed among older women might explain why they are not characterized by greater prevalent insomnia symptoms than their uninfected counterparts is anchored by evidence that psychological morbidity is the best predictor of insomnia in that population.6,37 Our multivariate analysis revealed that symptoms indicative of depression or taking antidepressants were independent predictors of the likelihood of reporting insomnia symptoms in all age strata. Other studies among persons with HIV infection have also demonstrated that insomnia is associated with a diagnosis of depression as well as symptoms of depression.6,37 According to data obtained from clinical interviews performed in accordance with guidelines from the Diagnostic and Statistical Manual of Mental Disorders, insomnia symptoms were associated with major depression, but not with CD4 SLEEP, Vol. 35, No. 1, 2012 135 Downloaded from https://academic.oup.com/sleep/article-abstract/35/1/131/2453859 by guest on 12 August 2018
count.37 Results of another study using the Hospital Anxiety and Depression Scale indicated that depression was an independent predictor of insomnia as well (OR = 1.17; 95% CI: 1.01-1.36).6 HIV-related clinical variables (e.g., duration of HIV infection, CD4 count, viral load, lipoatrophy, and HIV therapy type) were not significantly associated with insomnia symptoms. The finding that duration of HIV infection was not a significant correlate of insomnia symptoms seems consistent with the notion that insomnia is experienced throughout the course of HIV disease,1,6,26 but we acknowledge that specific characteristics of sleep morphology (i.e., sleep stages) may become disorganized in advanced stages of HIV disease.38 While our analysis demonstrated that duration of HIV infection was not a significant covariate, we could not examine whether the onset of HIV infection triggered the manifestation of insomnia symptoms or exacerbated existing sleep problems; such data were not elicited during initial interviews. We did not find significant associations of CD4 count, viral load, and lipoatrophy with insomnia symptoms. The observation that CD4 count (< 500 cells/mL) was not a significant correlate of insomnia symptoms is consistent with previous research demonstrating that CD4 count was not associated with self-reported sleep measures.12,26,37,39,40 Plausibly, low CD4 count relates only to a specific polysomnographic sleep measure (slow wave sleep), which undergoes marked changes in advanced stages of HIV disease.38,41 The finding that viral load was not significantly associated with insomnia symptoms was not surprising. Based on a study using the UCSF Symptom Management Conceptual model, investigators showed that sleep quality, measured by the Pittsburgh Sleep Quality Index, was not associated with viral load among individuals with HIV infection (mean length of infection = 8.5 years).12 An observational study conducted among HIV-infected patients showed that HIV-related symptoms that are likely to be associated with sleep measures include pain, fatigue, depression, state anxiety, but not CD4 count or viral load.40 It might have been assumed that worries about developing lipoatrophy would contribute to the likelihood of experiencing sleep problems.42 We found no associations between lipoatrophy and insomnia symptoms. In sum, our analysis suggests that these important immunologic and metabolic markers of HIV disease are not strong correlates of self-reported sleep measures. We have identified no systematic studies examining causal associations between utilization of HAART regimens and insomnia, although sleep disturbance is among the most common neuropsychiatric side effects associated with such regimens.43,44 A report from the AIDS Clinical Trials Group indicated that 56% of patients on antiretroviral regimens reported having insomnia, but the number of patients with insomnia did not necessarily decrease after ART discontinuation.44 Moreover, a report from the University of KwaZulu-Natal indicated that 56% of patients reported sleep disturbance as an adverse effect of HAART.43 Of note, 20% identified difficulty falling asleep as a reason for discontinuing their prescribed regimens.43 Other clinical studies suggested that use of efavirenz might cause increased difficulty initiating sleep (14%-20%).14,15,45 On balance, a more recent study showed that although patients reported an increase in nightmares and morning sluggishness after initiating efavirenz, overall they remained satisfied with their sleep.46 We did not investigate effects of specific Insomnia Symptoms and HIV Infection—Jean-Louis et al
drugs on insomnia symptoms, but we observed trends suggesting that women following HAART or non-HAART ARV regimens were more likely to report insomnia symptoms. Of interest was the observation that fewer women following HAART regimens reported insomnia symptoms, relative to those following nonHAART ARV regimens. It remains unclear whether utilization of antiretroviral therapies exacerbates existing sleep problems or induces them in at-risk patients. Our study has some limitations that should be considered in designing future epidemiologic sleep studies among individuals with HIV. One such limitation relates to the absence of data regarding insomnia-related daytime dysfunctions. This precluded the formulation of an insomnia diagnosis, but our focus was on symptoms, rather than diagnoses of insomnia. Plausibly, utilization of AASM diagnostic criteria for insomnia would have indicated that fewer women had insomnia. Another limitation of the study concerns the utilization of subjective data to estimate insomnia symptoms prevalence. Factors influencing subjective data might include selection bias, social desirability, and self-perceived sleep need. These findings may not be generalizable to men with HIV infection, as women are generally more likely than men to report insomnia symptoms.29,47 Despite these limitations, our study of insomnia symptoms in the context of HIV infection is very informative. It provides data that can be compared directly with estimates of the prevalence of insomnia symptoms in the general population.48,49 ACKNOWLEDGMENTS Data in this manuscript were collected by the Women’s Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is co- funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. DISCLOSURE STATEMENT This was not an industry supported study. Dr. Maki has received research support from Wyeth Pharmaceuticals. Dr. Levine owns stock in Genzyme Corporation. The other authors have indicated no financial conflicts of interest. REFERENCES
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