Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohor
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《英国医生杂志》
1 Basel Institute for Clinical Epidemiology, University Hospital Basel, Hebelstrasse 10, Basle, CH-4031, Switzerland, 2 Division of infectious Diseases and Hospital Hygiene, University Hospital Basel, 3 Institute of Nursing Science, University of Basel, Basle, 4 Division of Infectious Diseases, University of Zurich, Zurich, Switzerland, 5 Data Centre of the Swiss HIV Cohort Study, University of Lausanne, Lausanne, Switzerland, 6 Division of Infectious Diseases, University Hospital Berne, Berne, Switzerland, 7 Ambulattorio malattie infettive, Ospedale Civico, Lugano, Switzerland, 8 Division des maladies infectieuses, H?pital Universitaire de Genève, Geneva, Switzerland, 9 Division des maladies infectieuses, Centre Hospitalier Universitaire Vaudois, Lausanne, 10 Division of Internal Medicine, Cantonal Hospital Saint Gall, Saint Gall, Switzerland
Correspondence to: H C Bucher hbucher@uhbs.ch
Abstract
Cohort studies have shown that social relationships influence mortality. Having fewer close friends or relatives, less frequent contact with other people, and reduced social participation have all been associated with increased mortality, especially in elderly people and in men.1-4 People living alone have a higher mortality from cardiovascular disease and a poorer prognosis after a cardiac event.5 6 However, little is known about the impact of social relationships on outcome for people infected with HIV, most of whom are under 40 years old.
Social support, the emotional or tangible support available from other people, is one of the primary ways in which social relationships influence health.7 In particular, greater emotional support is strongly associated with lower mortality.3 8 Social support may have physiological effects on the neuroendocrine or immune systems.9 10 Poor social support has been linked to a more rapid decrease in CD4 cell counts in HIV infection.11 12 Social support may have psychological effects, such as reducing anxiety and depression.13 Social support may also moderate risk behaviours and improve adherence to treatment.14 15
Little is known about the effect of social support on outcome in HIV infection. Most definitions of social support emphasise family ties or social activities,16 and these may be less relevant for people living with HIV.17 For many people with HIV, a partner may be the most important source of emotional and tangible support. We investigated the association between a stable partnership and disease progression in HIV infected people receiving highly active antiretroviral therapy (HAART).
Methods
Participants
As of 28 February 2002, 5350 patients in the cohort had started HAART. We analysed data from the 3736 (70%) patients who had had CD4 cell counts (4130, 77%) and viral load (4041, 76%) measured within the three months before starting HAART and at least one follow up visit more than one month after starting HAART (5105, 95%). We followed these patients for a total of 12 173 patient years (median 3.6 years per patient).
Patients included in our analysis were on average similar in age, sex, and most likely source of infection (transmission group) to those excluded (table 1). However, those included were more likely to have a higher level of education (more than mandatory schooling), less likely to belong to ethnic groups other than white European, less likely to be in CDC group C, and more likely to have had antiretroviral therapy before starting HAART.
Table 1 Baseline characteristics for participants in the Swiss HIV cohort study on HAART and those in the analysis who did not reach the primary endpoint. Values are numbers (percentages) unless stated otherwise
When starting HAART, 52% (545/1042) of participants reported a stable partnership. This percentage decreased to around 46% (190/412) after five years of follow up (fig 1a). Beyond five years, estimates of the percentage reporting a stable partnership are unstable because they are based on a small sample; estimates based on a sample size of less than 30 are not shown. The decrease in the percentage reporting a stable partnership over time seems to be related to increasing age. The decrease was obvious among participants aged over 40 (fig 1c). The decrease in the percentage reporting a stable partnership was similar among participants in each of the three clinical stages at baseline (fig 1d). If infection with HIV made it more difficult to maintain a stable partnership, we might expect to see a more rapid decrease among sicker patients.
Fig 1 Proportion of participants reporting a stable partnership after starting highly active antiretroviral therapy (HAART): overall proportion (with 95% confidence interval) and sample size (dotted line) (top left); proportion for each sex (bottom left); proportion for each of three age groups (top right); and proportion for each clinical stage at baseline (bottom right)
Of the 3736 patients in our analysis, 2985 (80%) reported a stable partnership at least once during follow up. Those who had had antiretroviral therapy before starting HAART were likely to have registered earlier with the cohort and therefore had more time in which to form stable partnerships (table 2). Among the participants who had had previous antiretroviral therapy, the percentage reporting a stable partnership at least once was slightly higher for those at clinical stage A (484/565, 86%) than for those at stage C (416/511, 81%). This may reflect a higher mortality among patients who were sicker when starting HAART.
Table 2 Number (percentage) of participants in each stratum reporting stable partnership at least once
Of the 3432 (92%) participants who achieved optimal viral suppression (RNA < 400 copies/ml) at least once, 3360 (98%) had a CD4 cell count measured within the three months before they first achieved optimal suppression. We used these 3360 participants to estimate the association between stable partnership and the rate of progression to viral rebound.
Primary endpoint
Kaplan-Meier curves show that the initial rate of new disease or death was higher for patients starting HAART without previous antiretroviral therapy (fig 2). This is probably a result of immune restoration diseases (new disease within 90 days of starting HAART without previous antiretroviral therapy) rather than HIV progression.20 Log-log survival curves (not shown) for both baseline CDC group and previous antiretroviral therapy suggest that a proportional hazards assumption is not realistic for either variable.
Fig 2 Proportion of participants without new CDC group C disease or death over time after starting highly active antiretroviral therapy (HAART). Kaplan-Meier curves for each clinical stage (A, B, and C) at baseline for participants with previous antiretroviral therapy (top) and for those without previous antiretroviral therapy (bottom)
Across strata formed by each combination of baseline CDC group and previous antiretroviral therapy, a stable partnership was associated with a slower rate of progression to new CDC group C disease or death (hazard ratio 0.79, 95% confidence interval 0.63 to 0.98) (table 3). Exclusion of probable immune restoration diseases did not alter the result (hazard ratio 0.77, 0.61 to 0.97). We found no evidence of an interaction between stable partnership and either baseline CDC group (difference in log likelihood ratio 0.9, df = 2, P = 0.64) or previous antiretroviral therapy (0.1, df = 1, P = 0.74). This suggests that stable partnership had a similar association with disease progression in each stratum. Nor did we find any evidence that a stable partnership had a different association if it first occurred after April 2000 (difference in log likelihood ratio < 0.1, df = 1, P = 0.94), and our estimate of this association did not change when we included in our definition those reporting a stable partner without sexual intercourse. This indicates that the change in the way questions were asked did not materially influence our estimates of the association between stable partnership and disease progression.
Table 3 Cox proportional hazards model for time to new CDC group, stage C disease, or death
Estimates for covariates (table 3) show that the rate of progression to new CDC group C disease or death increased with increasing viral load at baseline, with increasing age, and among intravenous drug users but decreased with increasing CD4 count at baseline. We found no evidence that the association between disease progression and stable partnership was any different for intravenous drug users (difference in log likelihood ratio 0.49, df = 1, P = 0.48).
Of 3309 patients who did not experience new CDC group C disease or death, 2896 (88%) attended a follow up during the 12 months before 28 February 2002. We found no evidence of a "walking well" phenomenon, whereby patients with less severe disease were less likely to attend follow up. Compared with participants who had attended a recent follow up, those who had not were at a similar clinical stage at baseline, with similar baseline viral load and CD4 cell count (table 1).
Secondary endpoints
Stable partnership was associated with a decrease in the rate of progression to death and an increase in the rate of progression to CD4 cell counts of 50 and 100 above those recorded at baseline (table 4). We also found weaker evidence that stable partnership was associated with both an increase in the rate of progression to optimal viral suppression (hazard ratio 1.06, 0.98 to 1.14) and, in those achieving optimal suppression, with a decrease in the rate of progression to viral rebound (hazard ratio 0.91, 0.80 to 1.04).
Table 4 Adjusted hazard ratios for the association between stable partnership and each endpoint
Discussion
Seeman TE, Kaplan GA, Knudsen L, Cohen R, Guralnik J. Social network ties and mortality among the elderly in the Alameda County study. Am J Epidemiol 1987;126: 714-23.
Hanson BS, Isacsson SO, Janzon L, Lindell SE. Social network and social support influence mortality in elderly men: the prospective population study of "men born in 1914", Malmo, Sweden. Am J Epidemiol 1989;130: 100-11.
Berkman LF, Leo-Summers L, Horwitz RI. Emotional support and survival after myocardial infarction: a prospective, population-based study of the elderly. Ann Intern Med 1992;117: 1003-9.
Eng PM, Rimm EB, Fitzmaurice G, Kawachi I. Social ties and change in social ties in relation to subsequent total and cause-specific mortality and coronary heart disease incidence in men. Am J Epidemiol 2002;155: 700-9.
Case RB, Moss AJ, Case N, McDermott M, Eberly S. Living alone after myocardial infarction: impact on prognosis. JAMA 1992;267: 515-9.
Williams RB, Barefoot JC, Califf RM, Haney TL, Saunders WB, Pryor DB, et al. Prognostic importance of social and economic resources among medically treated patients with angiographically documented coronary artery disease. JAMA 1992;267: 520-4.
Berkman LF, Glass T, Brissette I, Seeman TE. From social integration to health: Durkheim in the new millennium. Soc Sci Med 2000;51: 843-57.
Penninx BW, van Tilburg T, Kriegsman DM, Deeg DJ, Boeke AJ, van Eijk JT. Effects of social support and personal coping resources on mortality in older age: the longitudinal aging study Amsterdam. Am J Epidemiol 1997;146: 510-9.
Berkman LF. The role of social relations in health promotion. Psychosom Med 1995;57: 245-54.
Uchino BN, Cacioppo JT, Kiecolt-Glaser JK. The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health. Psychol Bull 1996;119: 488-531.
Leserman J, Petitto JM, Golden RN, Gaynes BN, Gu H, Perkins DO, et al. Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS. Am J Psychiatry 2000;157: 1221-8.
Theorell T, Blomkvist V, Jonsson H, Schulman S, Berntorp E, Stigendal L. Social support and the development of immune function in human immunodeficiency virus infection. Psychosom Med 1995;57: 32-6.
Ingram KM, Jones DA, Fass RJ, Neidig JL, Song YS. Social support and unsupportive social interactions: their association with depression among people living with HIV. AIDS Care 1999;11: 313-29.
Kimberly JA, Serovich JM. The role of family and friend social support in reducing risk behaviors among HIV-positive gay men. AIDS Educ Prev 1999;11: 465-75.
Gordillo V, del Amo J, Soriano V, Gonzalez-Lahoz J. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS 1999;13: 1763-9.
Berkman LF, Syme SL. Social networks, host resistance, and mortality: a nine-year follow-up study of Alameda county residents. Am J Epidemiol 1979;109: 186-204.
Levine C. AIDS and changing concepts of family. Milbank Q 1990;68(suppl 1): 33-58.
Ancelle-Park R. Expanded European AIDS case definition. Lancet 1993;341: 441.
Glesby MJ, Hoover DR. Survivor treatment selection bias in observational studies: examples from the AIDS literature. Ann Intern Med 1996;124: 999-1005.
Ledergerber B, Egger M, Erard V, Weber R, Hirschel B, Furrer H, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV cohort study. JAMA 1999;282: 2220-6.
Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology 2000;11: 550-60.
Spire B, Duran S, Souville M, Leport C, Raffi F, Moatti JP. Adherence to highly active antiretroviral therapies (HAART) in HIV-infected patients: from a predictive to a dynamic approach. Soc Sci Med 2002;54: 1481-96.
Page-Shafer K, Delorenze GN, Satariano WA, Winkelstein W, Jr. Comorbidity and survival in HIV-infected men in the San Francisco men's health survey. Ann Epidemiol 1996;6: 420-30.
Johnson JG, Alloy LB, Panzarella C, Metalsky GI, Rabkin JG, Williams JB, et al. Hopelessness as a mediator of the association between social support and depressive symptoms: findings of a study of men with HIV. J Consult Clin Psychol 2001;69: 1056-60.
Frasure-Smith N, Lesperance F, Prince RH, Verrier P, Garber RA, Juneau M, et al. Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction. Lancet 1997;350: 473-9.(Jim Young, biostatisticia)
Correspondence to: H C Bucher hbucher@uhbs.ch
Abstract
Cohort studies have shown that social relationships influence mortality. Having fewer close friends or relatives, less frequent contact with other people, and reduced social participation have all been associated with increased mortality, especially in elderly people and in men.1-4 People living alone have a higher mortality from cardiovascular disease and a poorer prognosis after a cardiac event.5 6 However, little is known about the impact of social relationships on outcome for people infected with HIV, most of whom are under 40 years old.
Social support, the emotional or tangible support available from other people, is one of the primary ways in which social relationships influence health.7 In particular, greater emotional support is strongly associated with lower mortality.3 8 Social support may have physiological effects on the neuroendocrine or immune systems.9 10 Poor social support has been linked to a more rapid decrease in CD4 cell counts in HIV infection.11 12 Social support may have psychological effects, such as reducing anxiety and depression.13 Social support may also moderate risk behaviours and improve adherence to treatment.14 15
Little is known about the effect of social support on outcome in HIV infection. Most definitions of social support emphasise family ties or social activities,16 and these may be less relevant for people living with HIV.17 For many people with HIV, a partner may be the most important source of emotional and tangible support. We investigated the association between a stable partnership and disease progression in HIV infected people receiving highly active antiretroviral therapy (HAART).
Methods
Participants
As of 28 February 2002, 5350 patients in the cohort had started HAART. We analysed data from the 3736 (70%) patients who had had CD4 cell counts (4130, 77%) and viral load (4041, 76%) measured within the three months before starting HAART and at least one follow up visit more than one month after starting HAART (5105, 95%). We followed these patients for a total of 12 173 patient years (median 3.6 years per patient).
Patients included in our analysis were on average similar in age, sex, and most likely source of infection (transmission group) to those excluded (table 1). However, those included were more likely to have a higher level of education (more than mandatory schooling), less likely to belong to ethnic groups other than white European, less likely to be in CDC group C, and more likely to have had antiretroviral therapy before starting HAART.
Table 1 Baseline characteristics for participants in the Swiss HIV cohort study on HAART and those in the analysis who did not reach the primary endpoint. Values are numbers (percentages) unless stated otherwise
When starting HAART, 52% (545/1042) of participants reported a stable partnership. This percentage decreased to around 46% (190/412) after five years of follow up (fig 1a). Beyond five years, estimates of the percentage reporting a stable partnership are unstable because they are based on a small sample; estimates based on a sample size of less than 30 are not shown. The decrease in the percentage reporting a stable partnership over time seems to be related to increasing age. The decrease was obvious among participants aged over 40 (fig 1c). The decrease in the percentage reporting a stable partnership was similar among participants in each of the three clinical stages at baseline (fig 1d). If infection with HIV made it more difficult to maintain a stable partnership, we might expect to see a more rapid decrease among sicker patients.
Fig 1 Proportion of participants reporting a stable partnership after starting highly active antiretroviral therapy (HAART): overall proportion (with 95% confidence interval) and sample size (dotted line) (top left); proportion for each sex (bottom left); proportion for each of three age groups (top right); and proportion for each clinical stage at baseline (bottom right)
Of the 3736 patients in our analysis, 2985 (80%) reported a stable partnership at least once during follow up. Those who had had antiretroviral therapy before starting HAART were likely to have registered earlier with the cohort and therefore had more time in which to form stable partnerships (table 2). Among the participants who had had previous antiretroviral therapy, the percentage reporting a stable partnership at least once was slightly higher for those at clinical stage A (484/565, 86%) than for those at stage C (416/511, 81%). This may reflect a higher mortality among patients who were sicker when starting HAART.
Table 2 Number (percentage) of participants in each stratum reporting stable partnership at least once
Of the 3432 (92%) participants who achieved optimal viral suppression (RNA < 400 copies/ml) at least once, 3360 (98%) had a CD4 cell count measured within the three months before they first achieved optimal suppression. We used these 3360 participants to estimate the association between stable partnership and the rate of progression to viral rebound.
Primary endpoint
Kaplan-Meier curves show that the initial rate of new disease or death was higher for patients starting HAART without previous antiretroviral therapy (fig 2). This is probably a result of immune restoration diseases (new disease within 90 days of starting HAART without previous antiretroviral therapy) rather than HIV progression.20 Log-log survival curves (not shown) for both baseline CDC group and previous antiretroviral therapy suggest that a proportional hazards assumption is not realistic for either variable.
Fig 2 Proportion of participants without new CDC group C disease or death over time after starting highly active antiretroviral therapy (HAART). Kaplan-Meier curves for each clinical stage (A, B, and C) at baseline for participants with previous antiretroviral therapy (top) and for those without previous antiretroviral therapy (bottom)
Across strata formed by each combination of baseline CDC group and previous antiretroviral therapy, a stable partnership was associated with a slower rate of progression to new CDC group C disease or death (hazard ratio 0.79, 95% confidence interval 0.63 to 0.98) (table 3). Exclusion of probable immune restoration diseases did not alter the result (hazard ratio 0.77, 0.61 to 0.97). We found no evidence of an interaction between stable partnership and either baseline CDC group (difference in log likelihood ratio 0.9, df = 2, P = 0.64) or previous antiretroviral therapy (0.1, df = 1, P = 0.74). This suggests that stable partnership had a similar association with disease progression in each stratum. Nor did we find any evidence that a stable partnership had a different association if it first occurred after April 2000 (difference in log likelihood ratio < 0.1, df = 1, P = 0.94), and our estimate of this association did not change when we included in our definition those reporting a stable partner without sexual intercourse. This indicates that the change in the way questions were asked did not materially influence our estimates of the association between stable partnership and disease progression.
Table 3 Cox proportional hazards model for time to new CDC group, stage C disease, or death
Estimates for covariates (table 3) show that the rate of progression to new CDC group C disease or death increased with increasing viral load at baseline, with increasing age, and among intravenous drug users but decreased with increasing CD4 count at baseline. We found no evidence that the association between disease progression and stable partnership was any different for intravenous drug users (difference in log likelihood ratio 0.49, df = 1, P = 0.48).
Of 3309 patients who did not experience new CDC group C disease or death, 2896 (88%) attended a follow up during the 12 months before 28 February 2002. We found no evidence of a "walking well" phenomenon, whereby patients with less severe disease were less likely to attend follow up. Compared with participants who had attended a recent follow up, those who had not were at a similar clinical stage at baseline, with similar baseline viral load and CD4 cell count (table 1).
Secondary endpoints
Stable partnership was associated with a decrease in the rate of progression to death and an increase in the rate of progression to CD4 cell counts of 50 and 100 above those recorded at baseline (table 4). We also found weaker evidence that stable partnership was associated with both an increase in the rate of progression to optimal viral suppression (hazard ratio 1.06, 0.98 to 1.14) and, in those achieving optimal suppression, with a decrease in the rate of progression to viral rebound (hazard ratio 0.91, 0.80 to 1.04).
Table 4 Adjusted hazard ratios for the association between stable partnership and each endpoint
Discussion
Seeman TE, Kaplan GA, Knudsen L, Cohen R, Guralnik J. Social network ties and mortality among the elderly in the Alameda County study. Am J Epidemiol 1987;126: 714-23.
Hanson BS, Isacsson SO, Janzon L, Lindell SE. Social network and social support influence mortality in elderly men: the prospective population study of "men born in 1914", Malmo, Sweden. Am J Epidemiol 1989;130: 100-11.
Berkman LF, Leo-Summers L, Horwitz RI. Emotional support and survival after myocardial infarction: a prospective, population-based study of the elderly. Ann Intern Med 1992;117: 1003-9.
Eng PM, Rimm EB, Fitzmaurice G, Kawachi I. Social ties and change in social ties in relation to subsequent total and cause-specific mortality and coronary heart disease incidence in men. Am J Epidemiol 2002;155: 700-9.
Case RB, Moss AJ, Case N, McDermott M, Eberly S. Living alone after myocardial infarction: impact on prognosis. JAMA 1992;267: 515-9.
Williams RB, Barefoot JC, Califf RM, Haney TL, Saunders WB, Pryor DB, et al. Prognostic importance of social and economic resources among medically treated patients with angiographically documented coronary artery disease. JAMA 1992;267: 520-4.
Berkman LF, Glass T, Brissette I, Seeman TE. From social integration to health: Durkheim in the new millennium. Soc Sci Med 2000;51: 843-57.
Penninx BW, van Tilburg T, Kriegsman DM, Deeg DJ, Boeke AJ, van Eijk JT. Effects of social support and personal coping resources on mortality in older age: the longitudinal aging study Amsterdam. Am J Epidemiol 1997;146: 510-9.
Berkman LF. The role of social relations in health promotion. Psychosom Med 1995;57: 245-54.
Uchino BN, Cacioppo JT, Kiecolt-Glaser JK. The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health. Psychol Bull 1996;119: 488-531.
Leserman J, Petitto JM, Golden RN, Gaynes BN, Gu H, Perkins DO, et al. Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS. Am J Psychiatry 2000;157: 1221-8.
Theorell T, Blomkvist V, Jonsson H, Schulman S, Berntorp E, Stigendal L. Social support and the development of immune function in human immunodeficiency virus infection. Psychosom Med 1995;57: 32-6.
Ingram KM, Jones DA, Fass RJ, Neidig JL, Song YS. Social support and unsupportive social interactions: their association with depression among people living with HIV. AIDS Care 1999;11: 313-29.
Kimberly JA, Serovich JM. The role of family and friend social support in reducing risk behaviors among HIV-positive gay men. AIDS Educ Prev 1999;11: 465-75.
Gordillo V, del Amo J, Soriano V, Gonzalez-Lahoz J. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS 1999;13: 1763-9.
Berkman LF, Syme SL. Social networks, host resistance, and mortality: a nine-year follow-up study of Alameda county residents. Am J Epidemiol 1979;109: 186-204.
Levine C. AIDS and changing concepts of family. Milbank Q 1990;68(suppl 1): 33-58.
Ancelle-Park R. Expanded European AIDS case definition. Lancet 1993;341: 441.
Glesby MJ, Hoover DR. Survivor treatment selection bias in observational studies: examples from the AIDS literature. Ann Intern Med 1996;124: 999-1005.
Ledergerber B, Egger M, Erard V, Weber R, Hirschel B, Furrer H, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV cohort study. JAMA 1999;282: 2220-6.
Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology 2000;11: 550-60.
Spire B, Duran S, Souville M, Leport C, Raffi F, Moatti JP. Adherence to highly active antiretroviral therapies (HAART) in HIV-infected patients: from a predictive to a dynamic approach. Soc Sci Med 2002;54: 1481-96.
Page-Shafer K, Delorenze GN, Satariano WA, Winkelstein W, Jr. Comorbidity and survival in HIV-infected men in the San Francisco men's health survey. Ann Epidemiol 1996;6: 420-30.
Johnson JG, Alloy LB, Panzarella C, Metalsky GI, Rabkin JG, Williams JB, et al. Hopelessness as a mediator of the association between social support and depressive symptoms: findings of a study of men with HIV. J Consult Clin Psychol 2001;69: 1056-60.
Frasure-Smith N, Lesperance F, Prince RH, Verrier P, Garber RA, Juneau M, et al. Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction. Lancet 1997;350: 473-9.(Jim Young, biostatisticia)