Comparison of HIV-Infected Patients' Characteristics and Clinical Outcomes Between Cohort-Dependent and Independent Patients: Korean HIV Cohort Study

Abstract

To the Editors: Since the early 1980s, multicenter HIV cohort studies have been conducted worldwide, which have revealed valuable data on the clinical courses of HIV-infected patients. For example, such studies have helped to identify clinical/epidemiological features of the disease, types of opportunistic infections and malignancies more likely to be present in HIV-positive individuals, clinical outcomes and complications of diverse highly active antiretroviral therapy (HAART) regimens, patterns of antiretroviral resistance, and survival rates. Diverse community-based and multinational HIV/AIDS cohorts have been established: a Multicenter AIDS Cohort Study, the Swiss HIV Cohort, the Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, and the Collaborations in HIV Outcomes Research—US Cohort, etc.1-3 Although each HIV/AIDS cohort usually includes a large number of patients, ranging from 1000 to 15,000 subjects, some HIV-infected patients in cohort areas prefer not to join the cohort. The rate of participation in cohorts varies from one cohort to another and depends on the characteristics of the cohort's target population and local community (race, culture, economic status, etc). In this study, we intended to assess whether HIV-infected patients' characteristics and clinical outcomes were different between cohort-dependent and cohort-independent subjects at the early stages in a prospective HIV cohort in the era of HAART. The Korean HIV/AIDS HAART cohort opened in October 2006 and is composed of 5 university hospitals. All cohort-enrolled patients who initiated and maintained HAART for ≥12 months between February 2006 and January 2008 were compared with those who were on HAART for ≥12 months without enrollment in the cohort during the same period; patients who had undergone HAART before February 2006 were excluded. Patients' clinical and epidemiological data were retrieved from the cohort database and from individual medical records. Two trained monitors collected demographic, clinical, laboratory, and pharmaceutical data using structured case report forms that gathered information on age, sex, marital status, occupation, comorbidities, route of HIV transmission, time from initial diagnosis of HIV to HAART, history of sexually transmitted diseases and opportunistic diseases, HAART regimens, health care supplements, and adherence to treatment. Adherence to clinic visits was evaluated using a review of electronic medical records, revealing the number of missed clinical appointments (number per year) and the cumulative loss of time to follow-up (days per month). HAART was classified into 3 regimens: the boosted protease inhibitor (PI)-based regimen, the unboosted PI-based regimen, and the nonnucleoside reverse transcriptase inhibitor--based regimen. The CD4 T-cell count and HIV-1 RNA load were serially recorded, with values at baseline (at the time of HAART initiation), at 6 months (±2 weeks), and at 12 months (±2 weeks) after HAART initiation. The primary endpoint of the present study was to characterize the clinical and epidemiological features of cohort-dependent patients as compared with independent patients. In addition, we also evaluated the clinical impact of cohort enrollment on immunological and virological responses to HAART. Cohort-dependent patients were defined as subjects who deliberately agree to participate in the prospective Korean HIV/AIDS HAART Cohort Study. Cohort-independent patients were defined as either subjects who refused cohort enrollment or those whose doctors decide not to recommend enrollment because of a poor doctor-patient relationship or for any other reason. Data processing and evaluation were performed using SPSS 10.0 (SPSS, Inc., Chicago, IL). Categorical variables were analyzed by the χ2 test, and either the Student t test or the nonparametric test was used to compare continuous variables. All P values were 2 tailed, and P < 0.05 was considered to be statistically significant. A total of 35 of the 146 HIV cohort- enrolled patients (24.0%) were eligible for the study. Thirty-five cohort- dependent patients were compared with 33 independent patients. Sixteen of the 33 cohort-independent patients (48.5%) refused cohort enrollment despite a doctor's recommendation. All 6 female patients consented to cohort enrollment, but only about half (29 among 62, 46.8%) of the male patients consented to cohort enrollment (P = 0.01). There was no significant difference in age (45.1 ± 12.3 vs. 44.0 ± 10.7 years), marital status, occupation, route of transmission, history of comorbidities (14.3% vs. 19.2%), sexually transmitted diseases (28.6% vs. 23.1%), opportunistic infections (17.1% vs. 11.5%), and health care supplements (17.1% vs. 7.7%) between cohort-dependent and cohort-independent patients. In addition, there was no difference in time from the initial diagnosis of HIV to HAART (3.4 ± 1.3 vs. 3.7 ± 2.7 years), baseline CD4 T-cell counts (178.9 ± 113.7 vs. 167.7 ± 100.3 cells/μL), or mean viral loads before the initiation of HAART (5.00 ± 0.81 vs. 4.74 ± 0.51 log10 copies/mL) between the 2 patient groups (P > 0.05) (Table). Less than half of the patients in either the cohort- dependent or the cohort-independent patient groups remained married or obtained a permanent job. However, 35 cohort-dependent patients were less likely to miss clinical appointments (0.90 ± 0.92 vs. 1.42 ± 1.07, P = 0.05) compared with the 33 independent subjects; lost cumulative follow-up time was 1.42 ± 5.09 days and 3.36 ± 5.72 days, respectively (P = 0.15) (Table). The time from a CD4 T-cell count of <350 per cubic millimeter to HAART initiation was 67.3 ± 102.2 weeks (cohort-dependent patients) vs. 37.2 ± 53.8 weeks (cohort-independent patients) (P = 0.18). Boosted PI-based regimens were predominant among cohort-dependent patients (57.2%), whereas unboosted PI-based regimens were more common among cohort-independent patients (48.5%) (P = 0.02). As for the clinical outcomes after HAART, cohort-dependent patients showed better virological suppression as compared with the independent patients; viral load decreases (log10 RNA copies/mL) were 3.30 ± 1.07, as compared with 2.55 ± 1.32(P = 0.01) after 24 weeks of HAART, and 3.41 ± 1.00, as compared with 2.69 ± 1.42 (P = 0.02) after 48 weeks of HAART. Immunological responses were similar between cohort-dependent and cohort-independent patients, as measured up to 48 weeks after HAART initiation. CD4 T-cell counts (cells/mm3) were 220.0 ± 135.5, as compared with 173.3 ± 129.7 (P = 0.15) at 24 weeks of HAART, and 309.5 ± 220.6, as compared with 223.5 ± 181.9 (P = 0.10) after 48 weeks of HAART.TABLE: Comparison of Clinicoepidemiological Characteristics, Clinical Outcomes, and Adherence Patterns on HAART Between Cohort-Dependent and Cohort-Independent HIV-Infected PatientsThis is the first comparative study designed to assess the clinical and epidemiological differences between cohort-dependent and cohort-independent HIV-infected patients. In this study, we found that male subjects were more reluctant to participate in the cohort study. However, no social and economic factor was significantly different between cohort-dependent and cohort-independent subjects. Public discrimination against patients with HIV, concerns about the release of personal information, problems within the doctor-patient relationship, or other factors might have impacted their rate of cohort enrollment. To acquire representative data from HIV/AIDS cohort studies, active enrollment strategies that closely monitor and limit such barriers are required. Considering that baseline viral loads and CD4 T-cell counts were not significantly better among cohort-dependent patients, as compared with independent patients, the difference in clinical outcomes (suppression of viral loads) might be related to the type of HAART regimen and individual patient adherence patterns. Boosted PI-based regimens are known to show superior virological responses, as compared with unboosted PI-based regimens, independent of immunologic responses.4,5 This study was in agreement with these findings, as more of the cohort-dependent patients were treated with boosted PI-based regimens, and this group was found to have better virological responses. Only atazanavir (400 mg once daily) was prescribed as an unboosted PI, whereas either atazanavir/ritonavir (300/100 mg once daily) or lopinavir/ritonavir (400/100 mg twice a day) was given as a boosted PI. It is not clear why such a difference occurred, although we presume that the lower tolerability of unboosted atazanavir (requiring more tablets taken more times per day and with more gastrointestinal side effects) might contribute to a poor adherence pattern among cohort-independent patients. We assessed clinical adherence through the documentation of missed clinical appointments and cumulative loss of time to follow-up. Previously, Park et al reported that adherence to clinic visits was associated with clinical progress, independent of a patient's clinical category at the start of HAART.6 In this study, missed clinical appointments were more frequent, and cumulative loss of time to follow-up was somewhat greater in cohort-independent patients. It is possible that cohort enrollment itself promotes adherence to the HAART regimen. The long-term effects of cohort enrollment on virological response and antiretroviral drug resistance should be assessed in the future. In summary, cohort-dependent patients showed better adherence to treatment and better virological responses after treatment compared to cohort-independent patients. Joon Young Song, MD, PhD* Jin Soo Lee, MD, PhD† Hye Won Jeong, MD, PhD‡ Hee Jung Choi, MD, PhD§ Jin Seo Lee, MD‖ Jacob Lee, MD‖ Joong Shik Eom, MD, PhD‖ Hee Jin Cheong, MD, PhD* Moon Hyun Chung, MD, PhD† Woo Joo Kim, MD, PhD* *Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea †Inha University College of Medicine, Incheon, Korea ‡Chungbuk National University College of Medicine, Cheongju, South Korea §Ewha Womans University School of Medicine, Seoul, Korea ‖Hallym University College of Medicine, Seoul, Korea