Community Programs For Clinical Research On AIDS Research Articles

Non-adherence to antiretroviral therapy in Yaounde: Prevalence, determinants and the concordance of two screening criteria

To assess the prevalence and determinants of non-adherence to antiretroviral therapy (ART) as well as the concordance of two screening criteria in a major center for human immunodeficiency virus (HIV) treatment in Yaounde, Cameroon. In 2011, we conducted a cross-sectional study involving a random sample of 889 adults (age > 18 years, 67.9% women) infected with HIV who were receiving chronic care at the Yaounde Jamot Hospital. Adherence was assessed via self-administered questionnaires using the Community Programs for Clinical Research on AIDS (CPCRA) index and the Center for Adherence Support Evaluation (CASE) index. The prevalence of non-adherence to ART was 22.5% based on the CPCRA index and 34.9% based on the CASE index, with a low agreement between the two indexes [kappa = 0.37 (95% confidence interval 0.31-0.44)]. Independent determinants of CPCRA-diagnosed non-adherence were as follows: being a remunerated employee [odds ratio (95% confidence interval): 1.61 (1.14-2.28)], Pentecostal Christianity [2.18 (1.25-3.80)], alcohol consumption [1.65 (1.16-2.34)] and non-adherence to cotrimoxazole prophylaxis [5.73 (3.92-8.38)]. The equivalents for CASE-diagnosed non-adherence were [1.59 (1.19-2.12)], [1.83 (1.36-2.47)], [1.70 (1.27-2.28)], respectively, in addition to association with changes to the ART regimen [1.61 (1.17-2.20)]. Non-adherence to ART remains high in this population. The careful evaluation of patients for the presence of determinants of non-adherence identified in this study may aid ART optimization.

Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial

To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance. Secondary analysis of prospective clinical trial data. Participants randomized to the protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA more than 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis. Included were 457 and 446 antiretroviral-naive participants on the protease inhibitor and NNRTI strategies, respectively. The median time to initial virological failure in the protease inhibitor strategy was 1.2 years; 135 (30%) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28%) failed with resistance. No association was found between cumulative adherence and protease inhibitor resistance [hazard ratio 1.1, 95% confidence interval (CI) 0.9-1.4 per 10% lower adherence]. However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (hazard ratio 1.2, 95% CI 1.1-1.3 per 10% lower adherence). In both strategies, lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure. Adherence-resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence.

Effects of nurse‐delivered home visits combined with telephone calls on medication adherence and quality of life in HIV‐infected heroin users in Hunan of China

This study aimed to examine the effects of nurse-delivered home visits combined with telephone intervention on medication adherence, and quality of life in HIV-infected heroin users. Drug use is consistently reported as a risk factor for medication non-adherence in HIV-infected people. An experimental, pretests and post-tests, design was used: baseline and at eight months. A sample of 116 participants was recruited from three antiretroviral treatment sites, and 98 participants completed the study. They were randomly assigned to two groups: 58 in the experimental group and 58 in the control group. The experimental group received nurse-delivered home visits combined with telephone intervention over eight months, while the control group only received routine care. The questionnaire of Community Programs for Clinical Research on AIDS (CPCRA) Antiretroviral Medication Self-Report was used to assess levels of adherence, while quality of life and depression were evaluated using Chinese versions of World Health Organization Quality of Life Instrument-Abbreviated version (WHOQOL-BREF) and Self-rating Depression Scale, respectively. Data were obtained at baseline and eight months. At the end of eight months, participants in the experimental group were more likely to report taking 100% of pills (Fisher's exact = 14.3, p = 0.0001) and taking pills on time (Fisher's exact = 18.64, p = 0.0001) than those in the control group. There were significant effects of intervention in physical (F = 10.47, p = 0.002), psychological (F = 9.41, p = 0.003), social (F = 4.09, p = 0.046) and environmental (F = 4.80, p = 0.031) domains of WHOQOL and depression (F = 5.58, p = 0.02). Home visits and telephone calls are effective in promoting adherence to antiretroviral treatment and in improving the participants' quality of life and depressive symptoms in HIV-infected heroin users. It is important for nurses to recognise the issues of non-adherence to antiretroviral treatment in heroin users. Besides standard care, nurses should consider conducting home visits and telephone calls to ensure better health outcome of antiretroviral treatment in this population.

Adherence to highly active antiretroviral treatment and related factors in drug users with HIV/AIDS

Objective To explore adherence to highly active antiretroviral treatment(HAART)and related factors in dnlg users with HIV/AIDS.Methods From July to September 2007,111 HIV-infected drug users who received national free HAART were investigated in the HAART clinics in Hengyang,Yueyang,and Chenzhou districts of Hunan Province.A questionnaire of Community Programs for Clinical Research on AIDS(CPCRA)Antiretroviral Medication Self-Report Was used to assess adherence to HAART,and Zung Depression Scale and Adaptation Partnership Growth Affection Resolve Scale were used to assess patients'depression and family function respectively.ResllIts The average level of adherence to HAART was 83%.Among 111 patients.28.8%of patients reported poor adherence and took medication less than 90%.The mean score of depression was 60.8 1±13.03.There were 83.9%patients demonstrating depressive symptom and only 30.6%patients' family had good function.Logistic regression analysis showed that the degree of depression(β=-0.48,P=0.024)and treatment time(β=-1.11,P=0.036)were significantly associated with adherence negatively,while family function (β=0.65,P=0.043)and the time of being free from drug(β=0.55,P=0.040)were positively associated with adherence.Conclusion The level of adherence to HAART is low in the drug users with HIV/AIDS.Comprehensive interventions are needed to improve adherence to HAART,including managing depression,encouraging drug rehabilitation,improving family function,and evaluating adherence periodically. Key words: HIV/AIDS ; Drug abuse ; Hish active antiretroviral treatment ; Adherence ;

A random walk approach for quantifying uncertainty in group sequential survival trials

The development of group sequential methods has produced multiple criteria that are used to guide the decision of whether a clinical trial should be stopped early given the data observed at the time of an interim analysis. However, the potential for time-varying treatment effects should be considered when monitoring survival endpoints. In order to quantify uncertainty in future treatment effects it is necessary to consider future alternatives which might reasonably be observed conditional upon data collected up to the time of an interim analysis. A method of imputation of future alternatives using a random walk approach that incorporates a Bayesian conditional hazards model and splits the prior distribution for model parameters across regions of sampled and unsampled support is proposed. By providing this flexibility, noninformative priors can be used over regions of sampled data while providing structure to model parameters over future time intervals. The result is that inference over areas of sampled support remains consistent with commonly used frequentist statistics while a rich class of predictive distributions of treatment effect over the maximal duration of a trial are generated to assess potential treatment effects which may be plausibly observed if the trial were to continue. Selected operating characteristics of the proposed method are investigated via simulation and the approach is applied to survival data stemming from trial 002 of the Community Programs for Clinical Research on AIDS (CPCRA) study.

Self-Reported Adherence to Antiretroviral Treatment among HIV-Infected People in Central China

Although the number of patients receiving antiretroviral (ARV) therapy in Central China is expanding, little is known about their medication adherence. The purpose of this study was to: (1) describe adherence prevalence among patients receiving free ARV in south central China; (2) identify factors associated with adherence; (3) compare 3 self-report measures of adherence in this population. A cross-sectional survey was conducted at seven free treatment sites in Hunan, Hubei, and Anhui Provinces. Adherence measures included direct questioning regarding the number of doses taken in the 7 days prior to interview, the Community Programs for Clinical Research on AIDS (CPCRA) Adherence Self-Report questionnaire, and a 7-day visual analogue scale. Subjects comprised all patients returning for monthly ARV follow-up at each site between April and July 2006. Among the 308 subjects, 244 (79%) lived in the countryside. One hundred seventy (55%) had been on ARV over 1 year. No regimen included a protease inhibitor. Two hundred forty-four (80%) reported taking more than 90% of prescribed doses in the previous 7 days. Sixty-four (20%) subjects reported missing at least 1 dose in that period. The three measures of self-reported adherence were highly correlated. On multivariate analysis, current heroin use (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1,6, p = 0.05) and nonuse of reminders such as cell phone alarms, wall charts, or TV programs (OR 6; 95% CI 3, 11; p = 0.001) were associated with 90% or less adherence. Adherence to ARV in Central China is similar to elsewhere in the world. The 20% of subjects who reported taking 90% or fewer doses are of concern in view of the potential for non-nucleoside reverse transcriptase inhibitor resistance and lack of protease inhibitor back-up regimens. Substance abuse treatment will be an essential element of successful AIDS treatment in China. Prospective studies are needed to evaluate the efficacy of reminder devices to improve adherence in this population and to describe the prevalence and incidence of ARV resistance.

A Comparison of Factors Associated With Prevalent Diabetes Mellitus Among HIV-Infected Antiretroviral-Naive Individuals Versus Individuals in the National Health and Nutritional Examination Survey Cohort

In the general population, diabetes mellitus (DM) is associated with age, minority race/ethnicity, and obesity. Among HIV-infected persons, antiretroviral therapy (ART) use and hepatitis C virus (HCV) infection have been associated with DM. This study examined DM prevalence and its predictors in ART-naive HIV-infected patients. A cross-sectional analysis of ART-naive HIV-infected adults enrolled in 3 Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) clinical trials versus adults enrolled in the National Health and Nutritional Examination Survey (NHANES). The prevalence of DM in the CPCRA clinical trials versus the NHANES was 3.3% versus 4.8%. The mean body mass index (BMI) was lower in the CPCRA trials versus the NHANES (25 kg/m vs. 28 kg/m). HCV was associated with DM only in univariate analyses in the CPCRA trials. In univariate and multivariate analyses, race/ethnicity, age, and BMI were associated with DM in both cohorts. Among women, age and BMI were associated with DM in both cohorts; race/ethnicity was associated with DM only in the NHANES. HCV was predictive of DM in blacks in the CPCRA trials (P = 0.004 before adjustment for multiple comparisons) but not in the full cohort. Our findings did not suggest an increased prevalence of DM in ART-naive HIV-infected patients. Although there was a trend toward increased prevalence of DM in HIV-HCV-coinfected patients, dominant risk factors associated with DM among ART-naive HIV-infected adults mirrored those of the general population.

Eligibility criteria for HIV clinical trials and generalizability of results: the gap between published reports and study protocols

Applicability of randomized controlled clinical trial (RCT) results to 'real world' situations is dependent on the comparability of trial participants to general patient populations. A full disclosure of criteria employed for trial enrollment is necessary for clinicians to assess generalizability. We sought to assess both the impact on generalizability and the disclosure rate of enrollment criteria for 32 major HIV RCTs in the AIDS Clinical Trial Group (ACTG) and Community Programs for Clinical Research on AIDS (CPCRA) trial networks. Eligibility criteria were compared in complete protocols to criteria listed in publications from these 32 NIH-funded HIV RCTs. We then applied these criteria to the Women's Interagency HIV Study (WIHS), the largest cohort study of HIV-infected women in the US. When applied to WIHS, eligibility criteria from protocols excluded 0-67.6% (median 42%) of WIHS participants (50.6% excluded from ACTG trials). Eligibility criteria in publications excluded 0-62% (median 19.6%) of WIHS (21.2% excluded from ACTG trials). The number of women in WIHS seemingly ineligible for trial participation per enrollment criteria listed in publications averaged only 60% of those actually excluded based on the protocols. We found that HIV RCT eligibility criteria excluded a large proportion of a representative cohort of HIV-infected women from trial participation. Furthermore, trial publications are not fully reflective of protocols in terms of disclosing eligibility criteria. Standardization and full disclosure of trial methodology will allow clinicians and researchers to more fully assess the generalizability of findings to their patient populations.

Prevalence and characteristics of hepatitis C virus coinfection in a human immunodeficiency virus clinical trials group: the Terry Beirn Community Programs for Clinical Research on AIDS.

The baseline prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection among 2705 patients enrolled in HIV clinical trials in the Community Programs for Clinical Research on AIDS (CPCRA) was 16.6%. For men, multivariate logistic regression showed that the baseline prevalence of HIV-HCV coinfection was positively associated with history of injection drug use, older age, antiretroviral therapy naive status, African American or Latino ethnicity, and no history of having sex with men. No association was found with baseline CD4+ cell count or HIV RNA level. The prevalence of HCV coinfection in a diverse HIV clinical trials cohort provides additional information about risk behaviors and demographic factors that can be used in the analysis of clinical and virologic outcomes.

The Rationale and Design of the CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 058 FIRST (Flexible Initial Retrovirus Suppressive Therapies) Trial

The CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 058 FIRST (Flexible Initial Retrovirus Suppressive Therapies) trial is a large, long-term, randomized, prospective comparison of three different antiretroviral strategies in highly active antiretroviral therapy-naı̈ve, HIV-1-infected persons. The trial was designed as a flexible framework upon which other studies could be added to answer more limited, but still important, questions. This article presents the study design, discusses the challenges we have faced in implementing the trial, and describes our preliminary experiences. Control Clin Trials 2001;22:176–190

Kaposi's sarcoma and central nervous system disease: a real association or an artifact of the control group? Terry Beirn Community Programs for Clinical Research on AIDS.

To test the hypothesis that Kaposi's sarcoma (KS) protects against four central nervous system (CNS) diseases in HIV-1-infected individuals. The study population of 9404 subjects included participants in Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) protocols who were enrolled between September 1990 and September 1998. This was an observational study. Proportional hazards regression was used to estimate adjusted relative risks for predictors of four central nervous system diseases. Covariates included occurrence of Kaposi's sarcoma, occurrence of other opportunistic infections or malignancies, baseline CD4+ count, and other baseline characteristics. Among the 5944 participants without progression to AIDS at entry, 451 developed a CNS disease. The adjusted relative risk of any CNS disease for those who developed Kaposi's sarcoma versus those who did not develop any AIDS-defining event was 1.41 [95% confidence interval (CI), 0.98-2.03; P = 0.06]. In contrast, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.37 (95% CI, 0.24-0.57; P < 0.0001). Among the 3460 participants with progression to AIDS at entry, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.71 (95% CI, 0.40-1.25; P = 0.23). Our analyses indicate that the risk of CNS disease associated with Kaposi's sarcoma depends strongly on the reference or control group chosen. When compared to individuals with other non-Kaposi's sarcoma AIDS-defining diseases, Kaposi's sarcoma is associated with a lower risk of CNS disease in HIV-1 positive individuals. However, when compared to individuals with no AIDS-defining disease or with a similarly mild AIDS-defining disease such as invasive candidiasis, Kaposi's sarcoma is associated with an equivalent risk of CNS disease.

Data analysis issues for protocols with overlapping enrollment.

Many persons with HIV require and take several medications. The efficacy and safety of many of these medications are uncertain. Usually limited data on drug interactions are available. Thus simultaneous and sequential enrolment of patients into multiple studies is desired for reasons of science and efficiency. This paper discusses the analysis of data arising from coenrolment in multiple studies sponsored by the Community Programs for Clinical Research on AIDS (CPCRA). Factorial designs and those in which patients are sequentially instead of simultaneously randomized are compared. Approaches to data analysis, based on intention-to-treat, for individual and pairs of trials are described. An antiretroviral trial and a trial for prophylaxis of Pneumocystis carinii pneumonia (PCP) are used for illustration. We conclude that such analyses may yield useful information on drug interactions and that a more vigorous coenrolment policy should be pursued in AIDS research.

Two-Stage Tuberculin Skin Testing in Individuals with Human Immunodeficiency Virus Infection

In this study we estimated occurrence of the booster effect in a population infected with the human immunodeficiency virus (HIV) and assessed the relation between the booster effect, T-lymphocyte CD4 cell counts, tuberculosis risk categories, and HIV exposure categories. Patients were recruited from 13 participating sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A two-stage tuberculin skin test was applied to 709 HIV-infected patients using the Mantoux method. An induration reading < 5 mm on the first test and ≥ 5 mm on the second skin test defined the booster effect. Overall, 18 patients, or 2.7% (95% confidence interval, 1.6 to 4.2) experienced the booster effect. Boosted responses were seen in eight (2.1%) anergic patients, six (4.5%) nonanergic patients, and four (2.5%) with anergy status unknown. Boosting was noted in 1 of the 131 women enrolled. Age, race, CD4 cell count, injection drug use, anergy status, tuberculosis risk categories, and HIV exposure categories ...

Two-stage tuberculin skin testing in individuals with human immunodeficiency virus infection. Community Programs for Clinical Research on AIDS.

In this study we estimated occurrence of the booster effect in a population infected with the human immunodeficiency virus (HIV) and assessed the relation between the booster effect, T-lymphocyte CD4 cell counts, tuberculosis risk categories, and HIV exposure categories. Patients were recruited from 13 participating sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A two-stage tuberculin skin test was applied to 709 HIV-infected patients using the Mantoux method. An induration reading < 5 mm on the first test and > or = 5 on the second skin test defined the booster effect. Overall, 18 patients, or 2.7% (95% confidence interval, 1.6 to 4.2) experienced the booster effect. Boosted responses were seen in eight (2.1%) anergic patients, six (4.5%) nonanergic patients, and four (2.5%) with anergy status unknown. Boosting was noted in 1 of the 131 women enrolled. Age, race, CD4 cell count, injection drug use, anergy status, tuberculosis risk categories, and HIV exposure categories were not predictive of boosting. The booster effect occurs in a small percentage of HIV-infected patients tested, thus identifying small numbers of patients with latent tuberculosis infection. The two-stage procedure is probably of limited value in the diagnosis of latent tuberculosis in HIV-infected persons.

Issues of recruitment, retention, and compliance in community-based clinical trials with traditionally underserved populations

Site-specific sociodemographic recruitment, retention, and compliance (RRC) data were solicited at two points in time from the 18 National Institutes of Health-funded Community Programs for Clinical Research on AIDS (CPCRA). Based on their experiences delivering primary care to human immunodeficiency virus-infected individuals, nurses at each site identified organizational and client-centered factors functioning as barriers to protocol participation. In addition, the clinicians described the nature, frequency, and relative success of strategies used to enhance recruitment, retention, and protocol compliance. CPCRA units where nurses had clearly identified RRC barriers related to protocol design also were the sites that had accrued the most research participants. This study suggests that as the CPCRA units evolve, the most successful programs will be those in which the clinical and research staff can identify and develop innovative strategies that will successfully overcome RRC barriers.

Survival and Disease Progression According to Gender of Patients With HIV Infection

To compare disease progression and mortality between women and men infected with human immunodeficiency virus (HIV). Multicenter cohort. Seventeen community-based centers participating in the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A total of 768 women and 3779 men enrolled in one or more of 11 protocols between September 7, 1990, and September 30, 1993. Survival and opportunistic events. The median CD4+ cell count at enrollment into the cohort was 0.240 x 10(9)/L (240/microL) for women and 0.137 x 10(9)/L for men (P < .001). Compared with men, women were younger (36 vs 38 years), more likely to be African American or Hispanic (78% vs 44%), and more likely to have reported a history of injection drug use (49% vs 27%). Women had been followed up for a median of 14.5 months and men for 15.5 months. The adjusted relative risk (RR) for death among women compared with men was 1.33 (95% confidence interval [CI], 1.06 to 1.67; P = .01) and for disease progression (including death) was 0.97 (95% CI, 0.82 to 1.15; P = .72). Women were at increased risk for bacterial pneumonia (RR, 1.38; 95% CI, 1.05 to 1.92) and at reduced risk for the development of Kaposi's sarcoma (RR, 0.16; 95% CI, 0.04 to 0.65) and oral hairy leukoplakia (RR, 0.54; 95% CI, 0.31 to 0.94). The increased risk of death and bacterial pneumonia for women compared with men was primarily evident among those with a history of injection drug use (RR, 1.68 for death, 95% CI, 1.20 to 2.35, P = .003; RR, 1.53 for bacterial pneumonia, 95% CI, 1.03 to 2.29, P = .04). Among patients without a history of disease progression at entry, death was the first event reported for more women than men (27.5% vs 12.2%). Compared with men, HIV-infected women in the CPCRA were at increased risk of death but not disease progression. Risks of most incident opportunistic diseases were similar for women and men; however, women were at an increased risk of bacterial pneumonia. These findings may reflect differential access to health care and standard treatments or different socioeconomic status and social support for women compared with men.

Considerations in choice of a clinical endpoint for AIDS clinical trials. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).

In most clinical trials of antiretroviral therapy for patients infected with HIV, the major outcome variable has been the combined clinical endpoint of any new or recurrent AIDS defining event. We review features of combined endpoints and use data from the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) to evaluate this outcome measure in terms of relevance, diagnostic certainty and sensitivity. We conclude that this endpoint is not relevant because: (i) the 19 different events constituting the combined endpoint are equally weighted in analyses even though they vary considerably in terms of risk of death; and (ii) events after the first are ignored, thus the event profile of patients is not taken into account in making treatment comparisons. We also conclude that power may be low with use of this endpoint if treatments under study do not have an immediate impact on disease progression, if some events which occur soon after randomization represent a disease process that has already begun to incubate, or if treatment differences for the various events constituting the combined endpoint are differentially effected by treatment. Since the ease and certainty of diagnosis of each of the 19 events also vary, we recommend that survival be the primary endpoint of antiretroviral trials, and that all opportunistic events experienced by patients, not just the first, be collected and summarized. Trial reports should include comparisons of incidence of each event by treatment group so that readers can rank events as they please. A single summary measure which considers severity and the entire event profile, as described here, would also be useful for assessing the impact of treatments on quality of life. Further research on approaches for weighting and combining multiple outcome measures is needed.