JAIDS Journal of Acquired Immune Deficiency Syndromes:
The Association of Race, Sociodemographic, and Behavioral Characteristics With Response to Highly Active Antiretroviral Therapy in Women
Anastos, Kathryn MD*; Schneider, Michael F MS†; Gange, Stephen J PhD†; Minkoff, Howard MD‡; Greenblatt, Ruth M MD§; Feldman, Joseph PhD‡; Levine, Alexandra MD∥; Delapenha, Robert MD¶; Cohen, Mardge MD#; for the Women's Interagency HIV Study Collaborative Group
From the *Departments of Medicine and Epidemiology and Population Health, Montefiore Medical Center, Bronx, NY; †Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; ‡Department of Obstetrics and Gynecology, Maimonides Medical Center and SUNY Health Sciences Center at Brooklyn, New York, NY; §Departments of Medicine and Epidemiology, University of California at San Francisco, CA; ∥University of Southern California School of Medicine, Los Angeles, CA; ¶Department of Medicine, Howard University College of Medicine, Washington, DC; and #Cook County Hospital, Chicago, IL.
Received for publication October 4, 2004; accepted May 17, 2005.
The WIHS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute, the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, and the National Institute of Craniofacial and Dental Research (U01-AI-35004, U01-AI-31834, U01-AI-34994, AI-34989, U01-HD-32632, U01-AI-34993, U01-AI-42590, N01-AI-35161, RO1 AI48483).
Reprints: Kathryn Anastos, Women's Interagency HIV Study, 3311 Bainbridge Avenue, Bronx, NY 10467 (e-mail: firstname.lastname@example.org).
Objective: To determine the association of race with clinical and laboratory outcomes after initiation of highly active antiretroviral therapy (HAART) in HIV-1-infected women in the United States.
Study Design: Prospective cohort study.
Participants: A total of 961 HIV-1-infected women participating in the Women's Interagency HIV Study initiating HAART between July 1, 1995 and September 30, 2003.
Results: Over a median of 5.1 years of follow-up, in univariate Cox regression analyses, white women were more likely than African American women to attain a virologic response (relative hazard [RH] = 1.34, P = 0.005), less likely to experience viral rebound (RH = 0.76, P = 0.051), and less likely to die (RH = 0.63, P = 0.040). There were no significant differences, however, among racial groups in outcomes after adjustment for pre-HAART CD4+, HIV-1 RNA, history of AIDS-defining illness, age, antiretroviral therapy use, baseline HIV-1 exposure category, and post-HAART behavioral and clinical variables associated with poorer response (discontinuation of HAART, lower income, smoking, current drug use, and depression). Continuous HAART use and lack of depression differed by race and were the strongest predictors of favorable outcomes.
Conclusion: No significant differences by race were found in virologic, immunologic, or clinical outcomes after adjustment for continued HAART use and depression. These findings suggest that strategies to enhance HAART continuation, including assessing pharmacogenetic influences that may result in greater toxicity and discontinuation rates, and treating depression can improve individual and population-based effects of treatment and potentially mitigate racial disparities in AIDS-related outcomes.
The efficacy of antiretroviral therapies has been studied predominantly in men of European descent. Concern has been raised that differences in behavior or in biologically determined pathways of drug metabolism and transport, which vary by race,1-15 may impact unfavorably on response to highly active antiretroviral therapy (HAART) in groups other than white men. Although HAART has markedly improved the prognosis of HIV-1-infected individuals, not all demographic groups have benefited equally. In the United States, white men have experienced an 85% decline in mortality, compared with 50% and 65% declines in black women and men, respectively, from 1995 through 2001.16 Although some of this variation may result from differential access to HAART,17 the contribution of other factors, both behavioral and biologic, is not known.
Distrust of the health care system,17,18 spiritual beliefs, access to ongoing health care,18,19 differences in adherence,20,21 and biologic effects could all influence the population-based effectiveness of HAART. Some immunogenetic and pharmacogenetic characteristics differ by race and could alter the efficacy or toxicity (and therefore continuation) of treatment, through altered drug transport,1-6 drug metabolism,7-11 or immunopathogenetic mechanisms.12-15,22,23
There are significant challenges in investigating racial and ethnic differences in biomedical processes.24,25 Racial/ethnic categories are imprecise, overlap, and reflect “skin color, country of origin or ancestry, and language or dialect spoken”24 rather than genotype. Race in HIV-1 disease represents a risk marker, with a higher prevalence of HIV-1 infection in African Americans and Hispanics both in the United States and in the world. It may also be a true risk factor, with a direct etiologic relationship to HIV-1 disease progression or response to antiretroviral therapy (ART), derived from ancestral history and mediated in part or in toto by immunogenetic and pharmacogenetic mechanisms.
We investigated population-based responses to HAART stratified by self-categorized race in the Women's Interagency HIV Study (WIHS), with the understanding that there are limitations in data regarding race and ethnicity. Based on the previous finding that a polymorphism in the gene encoding P-glycoprotein (MDR1 position 3435 CC genotype) has been associated with increased P-glycoprotein activity, and is most frequent in people of African descent,1 we hypothesized that African American women would exhibit a poorer response to HAART even after adjustment for sociodemographic factors, continuation of HAART, and self-reported adherence. Throughout this report we have used the term “race” rather than “ethnicity” and attempted to define categories that adhere to ancestral history, acknowledging that such classification has inherent inaccuracies.
WIHS is a multicenter prospective cohort study of HIV-1 infection in women in 5 United States cities. WIHS methods have been described previously.26 Briefly, 2628 women (2059 HIV-1 seropositive and 569 seronegative) were enrolled in 1994 and 1995. Informed consent was obtained from all participants after approval by the committee on human experimentation at the collaborating institutions. Semiannually, WIHS participants were interviewed and examined, and laboratory specimens were obtained. After 5 years, the retention rate in the WIHS was approximately 80%.27
At each study visit, using photo medication cards, participants reported ART use since the previous visit. HAART was defined as combinations of ≥2 nucleoside reverse transcriptase inhibitors (NRTIs) with at least 1 protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI); 1 NRTI with at least 1 PI and at least 1 NNRTI; a regimen containing ritonavir and saquinavir in combination with 1 NRTI and no NNRTIs; and an abacavir-containing regimen of ≥3NRTIs (in the absence of both PIs and NNRTIs).28,29 Adherence measures previously described30 were introduced in October 1998. Participants were categorized dichotomously by whether or not they reported taking all drugs as prescribed at least 95% of the time.30
We estimated the time from HAART initiation to marker response (virologic and immunologic) and to onset of clinical events (incident AIDS-defining illness [ADI]), death, and death from AIDS. Additionally, we investigated the time from virologic response (HIV-1 RNA ≤80 copies/mL) to subsequent virologic failure (HIV-1 RNA >1000 copies/mL after virologic response) and the time from immunologic response (CD4+ lymphocyte counts ≥100 cells more than nadir pre-HAART CD4+) to subsequent immunologic failure (CD4+ lymphocyte counts below nadir pre-HAART level after immunologic response).
ADIs consistent with 1993 Centers for Disease Control surveillance definition, but excluding immunologic criterion of low CD4,31 were ascertained through self-report or confirmed through cancer and tuberculosis registries. Incident ADIs included any report of a clinical condition except cervical cancer, Kaposi sarcoma, non-Hodgkin lymphoma, tuberculosis, or wasting syndrome in women who had reported that specific illness prior to HAART initiation. ADIs reported at the same study visit at which HAART was first reported were not classified as incident.
Methods for ascertainment of cause and date of death have been described previously.32
The primary exposure of interest was self-categorized race, defined as African American (Hispanic and non-Hispanic), white (Hispanic and non-Hispanic), and Hispanic (women identifying as Hispanic but neither African American nor white).
Plasma HIV-1 RNA was measured using the isothermal nucleic acid sequence-based amplification method (Nuclisens, Organon Teknika Corp., Durham, NC) with a lower limit of detection of 80 copies/mL. Lymphocyte subsets were quantified using standard flow cytometric methods in laboratories participating in the National Institutes of Health/National Institute of Allergy and Infectious Diseases Flow Cytometry Quality Assessment Program.33
We investigated responses after HAART initiation using Cox regression. Univariate models assessed the differences in virologic, immunologic, and clinical outcomes among the 3 racial groups. Multivariate models measured heterogeneity in outcomes by race, adjusting for pre-HAART variables of self-reported ADIs, nadir CD4+ count, peak HIV-1 RNA, age, prior ART use, and self-reported HIV-1 exposure category. We adjusted for post-HAART time-varying exposures of continued HAART use, depression, income, cigarette smoking, current drug use, and adherence. Depression was defined as a score of ≥16 on the Center for Epidemiologic Studies Depression scale, at the same visit at which the outcomes were measured.34
Of the 2059 HIV-1-seropositive women, 1277 (62.0%) initiated HAART, and 961 (75.3%) met all selection criteria (Fig. 1). The median follow-up after HAART initiation was 5.1 years (interquartile range, 3.2-6.3 years).
The 961 participants included 573 (59.6%) African American, 184 (19.2%) white, and 204 (21.2%) Hispanic women. African American women were older, less educated, initiated HAART at later calendar times, and were more likely to report pre-HAART use of cigarettes and cocaine, crack, or heroin than white women (Table 1). Hispanic women were more likely to be depressed, to have an annual income of ≤$12,000, not to have completed high school, and to report not using ART at ≥1 visits after HAART initiation (55.4%), compared with white (27.7%) and African American women (44.7%) (Table 1).
Univariate and Multivariate Analyses of Laboratory and Clinical Outcomes
Table 2 presents the number (and percentage) of women in each ethnic group with each outcome after HAART initiation. White women exhibited better immunologic and virologic response and lower rates of immunologic and virologic failure, AIDS defining illnesses, and all-cause and AIDS deaths.
In univariate analyses of the hazard of each of the outcomes after HAART initiation (Table 3, model 1), white women were more likely than African American women to experience virologic response (relative hazard [RH] = 1.34, P = 0.005), less likely to experience virologic rebound (RH = 0.76, P = 0.051), and less likely to die of any cause (RH = 0.63, P = 0.040). Figure 2 shows the estimated cumulative survival stratified by race. After nearly 8 years, African American women were less likely to survive (70.0%) compared with white (80.0%) and Hispanic women (76.5%).
Also shown in Table 3 are multivariate Cox regression analyses adjusted for pre-HAART exposures including ART use, age (per 10 years), ADI, nadir CD4+ cell count, peak HIV-1 RNA, HIV-1 exposure category (model 2), and for time-varying post-HAART exposures of depression, drug use, cigarette smoking, income (model 3), and post-HAART antiretroviral therapy use (model 4). In model 2, white women remained more likely than African Americans to experience virologic response and less likely to have virologic rebound. After including continued ART use following HAART initiation (model 4), however, there were no significant differences by race in virologic, immunologic, or clinical responses to HAART, although there were trends (0.050 ≤ P < 0.100) toward better immunologic response in white women and lower incidence of new ADIs in Hispanic women.
Table 4 presents the impact of each exposure (included in model 4) on the 7 different outcomes. Continued HAART use was the strongest predictor of favorable virologic, immunologic, and clinical responses, with a 16-fold increased likelihood of virologic response and an approximately two-thirds decreased risk of experiencing virologic or immunologic failure or death from AIDS. Because of this strong association with continued HAART use, we performed additional analyses limited to the 541 women who did not report discontinuing ART use at any time after HAART initiation (Table 3, model 5). There were no significant differences by race in any of the assessed outcomes after restricting analyses to women who remained on ART or HAART.
Depression (Table 4) was significantly associated with poorer virologic response, increased likelihood of immunologic failure, incident ADI, and a higher risk of all-cause, but not AIDS-related, death. Current drug use was associated with death from AIDS and a greater risk of incident ADI.
Bivariate Analyses of Race and Adherence
Since we had collected detailed adherence data only at study visits after October 1998, we analyzed the association of adherence with both laboratory and clinical outcomes, while adjusting for race (Table 3, model 6). Among the 297 women (30.9%) with adherence data at HAART initiation, we found no statistically significant differences (P = 0.845) between adherence to therapy at HAART initiation and race (Table 1). At least 73% of each racial group reported at least 95% adherence. Higher adherence was strongly associated with favorable virologic and immunologic responses and with reduced risk of a new ADI (Table 4).
Bivariate Analyses of Race and Depression on HAART Discontinuation
Depression reported following HAART initiation was associated with HAART discontinuation (RH = 1.40, P = 0.004). Race, however, was the stronger predictor of discontinuation, with white women less than half as likely as African American (RH = 0.43, P < 0.001) or Hispanic women (RH = 0.32, P < 0.001) to discontinue therapy independent of depression (data not shown). Thus, the higher prevalence of depression did not explain the higher rate of HAART discontinuation in African American and Hispanic women.
HIV infection, hypertension, diabetes, and trauma are responsible for most of the 6-year lower life expectancy of African Americans compared with whites in the United States.35 HIV disease accounts for 11.2% of the disparity, almost as much as ischemic heart disease (5.5%), stroke (2.8%), and cancer (3.4%) combined.35 In our study investigating the relationship of race with response to HIV-1 treatment among 961 women initiating HAART, white women had more favorable virologic, immunologic, and clinical responses to HAART. The poorer responses to HAART found in African American and Latina women, however, were explained largely by HAART discontinuation and to a lesser extent, by depression. Although discontinuation of therapy may be secondary to toxicity that results from specific genetic determinants of drug metabolism and transport, both depression and therapy discontinuation are potentially mutable. This suggests that treating depression and ascertaining and addressing reasons for treatment discontinuation could substantially improve outcomes in African American and Latina women.
Pharmacokinetics of antiretroviral agents is influenced by genetically determined factors that vary by individual ancestral history. Several studies have demonstrated that African Americans experience higher toxicity and higher rates of discontinuing therapy.8,10,11 For example, investigators have found slower clearance or higher rates of central nervous system toxicity and discontinuation of efavirenz associated with polymorphisms of the 2B6 pathway of the cytochrome P450 system.10,11 Thus, biologic mechanisms resulting in greater drug toxicity may account for the racial differences we found in HAART discontinuation.
Polymorphisms in MDR1, the gene that codes for P-glycoprotein (P-gp), also vary by race.1-6 P-gp is a transport protein that exports its substrates out of cells, raising concern that the efflux of antiretroviral agents from the cell could result in both greater toxicity and lower efficacy. Although Africans, Asians, Europeans, and African and European Americans have been shown to differ in the proportion of specific polymorphisms at 2 alleles in MDR1,1-6 the influence of these polymorphisms on drug levels or the efficacy and toxicity of treatment is controversial. Some studies indicate a clinical difference,1-3,5 whereas others do not.4,36 It remains worrisome, however, that the direction of all differences in our study favored white women. Indeed, the relative hazard of 0.49 for death from AIDS (Table 3, model 5) in white compared with African American women who continued on therapy, would be very significant clinically, if real (P = 0.193 in our study). Host genetic variations in factors that influence bioavailability and clearance of antiretroviral drugs may contribute to racial differences in outcomes after HAART initiation, either directly by limiting bioavailability, or indirectly by influencing HAART continuation or adherence, and deserve further study. Of note, the clinical effects of the pharmacogenetic mechanisms described here are unpredictable, will not be the same for all of the currently approved antiretroviral agents, and would not be expected to influence regimens consisting entirely of NRTIs.
Racial disparities in health outcomes, including HIV-1-related illness, have also been attributed to social determinants such as lower socioeconomic status, lower educational attainment, and differential access to and quality of health care services.17,18,37-43 Even in a setting of a national universal health care system, lower socioeconomic status was shown to be associated with reduced access to HAART. Among HAART recipients, however, socioeconomic status did not affect virologic response.42 Similarly, in the United States, where health care is not universally available, HIV-1-infected persons of color are less likely to receive antiretroviral therapy when indicated40,41 or to access state entitlement programs.39,40 In our study, although we focused on women who reported initiating and thus had some access to HAART, the differences in therapy continuation may be associated with more subtle and complex differences in access to and quality of care that we were unable to measure.
The association of HAART discontinuation with depression suggests that identification and treatment of depression can improve the effect of HAART. We and others have previously reported that depression predicted HAART discontinuation,44 poorer laboratory responses45 while on antiretroviral therapy, and a greater likelihood of AIDS-related deaths and that treatment of depression was associated with reduced mortality.46,47 However, the association of race with HAART discontinuation was not explained by depression, suggesting that ascertaining and rectifying the causes of discontinuing indicated therapy by women of color could also improve their response to HAART. Our current findings also support studies that have found no difference by race in immunologic48 or virologic responses.41 Adherence was associated with better responses in our study, but adherence did not vary by race. This is in contrast to some prior studies in populations mostly or exclusively male, in which white race was associated with higher rates of adherence.49-51 It is possible that our ascertainment of adherence did not completely describe differences by race or that such differences are less marked in women. Further investigation is warranted.
The Institute of Medicine Report concluded that there is “clear and convincing evidence for racial disparities in health care” in the United States.52 Some of this disparity may be attributable to difficulties in communication: whites are half as likely as Latinos in the United States to perceive difficulty communicating with their physician, and one-third less likely than African Americans.53 Latinos and African Americans are less likely to trust their provider to diagnose and choose therapy in the patient's best interest.54 These mechanisms could influence HAART discontinuation and the diagnosis and treatment of depression. An important next step will be to ascertain directly from patients their reasons for discontinuing HAART.
A limitation of our study is the low rate of HIV-related clinical outcomes after HAART initiation, particularly in AIDS deaths (16 per 1000 person-years), limiting our ability to rule out a clinically significant difference by race in clinical outcomes. A methodologic limitation of our study is that some of the exposures, specifically depression and HAART discontinuation, were ascertained at the same visit as the virologic and immunologic endpoints. In addition, HAART discontinuation could have been the result of virologic or immunologic failure, rather than the cause. The very large relative hazards, the strength of the association of HAART continuation with both laboratory and clinical outcomes, and similar findings when analyses were limited to women who continued HAART, however, suggest that some or even most of the improvement in outcomes results from the continuation of therapy. These analyses complement our other reports demonstrating the consequences of HAART discontinuation.55,56
Another significant limitation of our study, as in most studies that attempt to investigate the impact of race, is the impossibility of defining race as a biologic construct. We used women's self-classification of race and ethnicity to group them by common ancestry, comparing all women self-identifying as “black” (of African ancestry) with all women self-identifying as white (of European ancestry). In addition, there were 204 women self-identifying as Hispanic, a term that defines ethnicity and not race, but not identifying themselves as either black or white, and for whom there were some significant differences in baseline characteristics and in clinical outcomes. As reviewed recently,57 ancestrally determined differences in drug transport or metabolism may carry clinical significance, and the large majority of studies of the efficacy and tolerability of antiretroviral regimens have been performed in populations of predominantly European ancestry. The trend toward poorer outcomes in African American and Latina women, especially AIDS-related deaths, deserves further investigation with longer follow-up in this and other cohorts, to confirm that there is not a significant difference by race. Also important for HIV-1-infected African American and Latina women in the United States is the diagnosis and treatment of depression and exploration and rectification of the factors related to HAART discontinuation, as these may be contributing substantially to poorer health status, including death, among HIV-infected women of color.
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 (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). Participating institutions approved this study and consent forms provided to study participants.
1. Schaeffeler E, Eichelbaum M, Brinkmann U, et al. Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet
2. Kim RB, Leake BF, Choo EF, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther
3. Ameyaw MM, Regateiro F, Li T, et al. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics
4. Haas DW, Wu H, Li H, et al. MDR1 gene polymorphisms and phase 1 viral decay during HIV-1 infection: an Adult AIDS Clinical Trials Group study. J Acquir Immune Defic Syndr
5. Fellay J, Marzolini C, Meaden ER, et al. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet
6. Marzolini C, Paus E, Buclin T, et al. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther
. 2004;75:13-33. Review.
7. Baede-van Dijk PA, Hugen PW, Verweij-van Wissen CP, et al. Analysis of variation in plasma concentrations of nelfinavir and its active metabolite M8 in HIV-positive patients. AIDS
8. Haas DW, Ribaudo HJ, Kim RB, et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS
9. Barrett JS, Joshi AS, Chai M, et al. Population pharmacokinetic meta-analysis with efavirenz. Int J Clin Pharmacol Ther
10. Ribaudo H, Clifford D, Gulick R, et al. Relationships between efavirenz pharmacokinetics, side effects, drug discontinuation, virologic response, and race: results from ACTGA5095/A5097s. Abstract 132. Paper presented at: 11th Conference on Retroviruses and Opportunistic Infections; 2004; San Francisco, February 8-11, 2004.
11. Pfister M, Labbe L, Hammer SM, et al. Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and indinavir: Adult AIDS Clinical Trial Group Study 398. Antimicrob Agents Chemother
12. Tarr PE, Taffe P, Bleiber G, et al. Modeling the influence of APOC3, APOE,
polymorphisms on the risk of antiretroviral therapy associated lipid disorders. J Infect Dis
13. Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7,
and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet
14. Hetherington S, Hughes AR, Mosteller M, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet
15. Martin AM, Nolan D, Gaudieri S, et al. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701
and a haplotypic Hsp70-Hom
variant. Proc Natl Acad Sci USA
16. Centers for Disease Control and Prevention. AIDS/HIV Surveillance Report, Year End Edition 2001
. Atlanta: Centers for Disease Control and Prevention; 2002.
17. Kahn JG, Zhang X, Cross LT, et al. Access to and use of HIV antiretroviral therapy: variation by race/ethnicity in two public insurance programs in the U.S. Public Health Rep
18. Pickle K, Quinn SC, Brown JD. HIV/AIDS coverage in Black newspapers, 1991-1996: implications for health communication and health education. J Health Commun
19. Klein D, Hurley LB, Merrill D, et al. Review of medical encounters in the 5 years before a diagnosis of HIV-1 infection: implications for early detection. J Acquir Immune Defic Syndr
20. Stone VE, Hogan JW, Schuman P, et al. Antiretroviral regimen complexity, self-reported adherence, and HIV patients' understanding of their regimens: survey of women in the HERS study. J Acquir Immune Defic Syndr
21. Ferguson TF, Stewart KE, Funkhouser E, et al. Patient-perceived barriers to antiretroviral adherence: associations with race. AIDS Care
22. Hulgan T, Donahue JP, Hawkins C, et al. Implications of T-cell P-glycoprotein activity during HIV-1 infection and its therapy. J Acquir Immune Defic Syndr
23. Gao X, Nelson GW, Karacki P, et al. Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N Engl J Med
24. Kaplan JB, Bennett T. Use of race and ethnicity in biomedical publications. JAMA
25. Osborne NG, Feit MD. The use of race in medical research. JAMA
26. Barkan SE, Melnick SL, Preston-Martin S, et al. The Women's Interagency HIV Study. WIHS Collaborative Study Group. Epidemiology
27. Hessol NA, Schneider M, Greenblatt RM, et al. Retention of women enrolled in a prospective study of human immunodeficiency virus infection: impact of race, unstable housing, and use of human immunodeficiency virus therapy. Am J Epidemiol
28. Carpenter CCJ, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA
29. DHHS/Henry J. Kaiser Family Foundation Panel on Clinical Practices for the Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Available at: http://hivatis.org
. Accessed April 20, 2004.
30. Wilson T, Barron Y, Cohen MH, et al. Adherence with antiretroviral therapy and associations with sexual behavior. Clin Infect Dis
31. Centers for Disease Control and Prevention. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep
32. Cohen MH, French A, Benning L, et al. Causes of death among women with human immunodeficiency virus infection in the era of combination antiretroviral therapy. Am J Med
33. Calvelli T, Denny T, Paxton H, et al. Guidelines for flow cytometric immunophenotyping. Cytometry
34. Bozzette SA, Hays RD, Berry SH, et al. Derivation and properties of a brief health status assessment instrument for use in HIV disease. J Acquir Immune Defic Syndr
35. Wong MD, Shapiro MF, Boscardin J, et al. Contribution of major diseases to disparities in mortality. N Engl J Med
36. Nasi M, Borghi V, Pinti M, et al. MDR1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients. AIDS
37. Palacio H, Khan JG, Richards TA, et al. Effect of race and/or ethnicity in use of antiretrovirals and prophylaxis for opportunistic infection: a review of the literature. Public Health Rep
38. Cohen MH, Cook JA, Grey D, et al. Medically eligible women who do not use HAART: the importance of abuse, drug use and race. Am J Public Health
39. Sterling TR, Chaisson RE, Moore RD. HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy. AIDS
40. Chan D, Absher D, Sabatier S. Recipients in need of ancillary services and their receipt of HIV medical care in California. AIDS Care
. 2002;14(Suppl 1):S73-S83.
41. Jensen-Fangel S, Pedersen L, Pedersen C, et al. The effect of race/ethnicity on the outcome of highly active antiretroviral therapy for human immunodeficiency virus type 1-infected patients. Clin Infect Dis
42. Wood E, Montaner JS, Chan K, et al. Socioeconomic status, access to triple therapy, and survival from HIV-disease since 1996. AIDS
43. Yamashita TE, Phair JP, Munoz A, et al. Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study. AIDS
44. Grant LA, Tarwater PM, Schneider MF, et al. Factors and temporal trends associated with HAART discontinuation in the Women's Interagency HIV Study. J Acquir Immune Defic Syndr
45. Parienti JJ, Massari V, Descamps D, et al. Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. Clin Infect Dis
46. Cook JA, Cohen M, Burke J, et al. Depressive symptoms and mental quality of life as predictors of utilization of HAART in a cohort of HIV-seropositive women. J Acquir Immune Defic Syndr
47. Cook JA, Grey D, Burke J, et al. Depressive symptoms and AIDS-related mortality among a multisite cohort of HIV-positive women. Am J Public Health
48. Giordano TP, Wright JA, Hasan MQ, et al. Do sex and race/ethnicity influence CD4 cell response in patients who achieve virologic suppression during antiretroviral therapy? Clin Infect Dis
49. Mannheimer S, Friedland G, Matts J, et al. The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis
50. Kleeberger CA, Buechner J, Palella F, et al. Changes in adherence to highly active antiretroviral therapy medications in the Multicenter AIDS Cohort Study. AIDS
51. Kleeberger CA, Phair JP, Strathdee SA, et al. Determinants of heterogeneous adherence to HIV-antiretroviral therapies in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr
52. Smedley BD, Stith AY, Nelson A, eds. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care
. Washington, DC: National Academies Press; 2002.
53. Davis K, Schoenbaum S, Collins KS, et al. Room for Improvement: Patients Report on the Quality of Their Health Care
. Commonwealth Fund 2001 Healthcare Quality Survey
. New York: The Commonwealth Fund; 2002.
54. Doty MM. Hispanic Patients' Double Burden
: Lack of Health Insurance and Limited English
. New York: The Commonwealth Fund; 2003.
55. Grant LA, Silverberg MJ, Palacio H, et al. Discontinuation of potent antiretroviral therapy: predictive value of and impact on CD4 cell counts and HIV RNA levels. AIDS
56. Barrón Y, Cole SR, Greenblatt RM, et al. Effect of discontinuing antiretroviral therapy on survival of women initiated on highly active antiretroviral therapy. AIDS
57. Haas DW. Pharmacogenomics and HIV therapeutics (editorial comment). J Infect Dis
Race differences; HIV; highly active antiretroviral therapy; survival; women
© 2005 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
Data is temporarily unavailable. Please try again soon.