Administration Of Highly Active Antiretroviral Therapy Research Articles

Favorable Impact of Virological Response to Highly Active Antiretroviral Therapy on Survival in Patients with AIDS-related Lymphoma

We have retrospectively studied the influence of highly active antiretroviral therapy (HAART) on the outcome of AIDS-related lymphomas (ARL) as well as the possible influence of the virological response to HAART on complete response (CR) rate and survival in our series of ARL treated with CHOP. Two groups of patients were studied: (1) 44 patients who did not take HAART when the lymphoma was diagnosed, and (2) 26 patients treated with HAART concomitantly and after chemotherapy. There were 4 (9%) women in group 1 versus 11 (42%) in group 2 (P =0.01), and serum lactate dehydrogenase (LDH) level was lower in group 2. The response rate to CHOP was higher in group 2 patients (15 out of 23, 65%) than in those of group 1 (16 out of 44, 36%) (P =0.025). The factors associated with improvement of CR in the multivariate analysis were the administration of HAART (P =0.004) and International Prognostic Index (IPI) score ≤ 2 (P =0.006). Among group 2 patients, those with a virological response to HAART and with IPI score ≤ 2 had better response rate to chemotherapy (odds ratios 9.3 and 11.8, respectively). The median (95% CI) overall survival (OS) for group 1 patients was 7 (3-11) months, whereas it has not been reached for group 2 (P =0.002). The only parameters influencing OS in the multivariate analysis were HAART (0.003), as a protective factor and IPI score>2 (P =0.015) with negative influence. Among patients treated with HAART, those with virological response had higher OS probability (P =0.004), whereas those with IPI score>2 had an unfavorable prognosis (P =0.014). The only variable with statistical significance for disease free survival (DFS) in the univariate and multivariate analyses was HAART (P =0.0168 and P =0.028, respectively). We conclude that HAART is an independent prognostic factor for CR attainment, OS and DFS in patients with ARL treated with CHOP. Those patients with virological response to HAART had a better survival.

Antiretroviral therapy-associated hyperlipidaemia in HIV disease.

Widespread utilization of highly active antiretroviral therapy (HAART) for HIV-infection, primarily protease inhibitors in combination with nucleoside analogue reverse transcriptase inhibitors, has recently led to a sustained reduction in the morbidity and mortality of this disease. However, administration of HAART is frequently associated with the development of lipid disorders. The severity and prevalence of dyslipidaemia vary, depending on the type of HAART, nutritional status, HIV disease stage, and concomitant presence of lipodystrophy and insulin resistance (two additional adverse effects of HAART). The mechanism that is responsible for HAART-associated dyslipidaemia remains incompletely understood. Recent data indicate that this effect may be, at least in part, accounted for by protease inhibitor-mediated inhibition of the proteasome activity and accumulation of the active portion of sterol regulatory element-binding protein-1c in liver cells and adipocytes. Whether lipid disorders in HIV-infected patients receiving HAART translate into an increased cardiovascular risk, and the indications for lipid-lowering interventions in this population, remain to be established.

Health Care Resource Utilization in the Johns Hopkins HIV Clinic Cohort

The introduction of highly active antiretroviral therapy (HAART) has been shown to decrease mortality rates and human immunodeficiency virus (HIV)-associated morbidity. In this review of resource utilization among HIV-infected persons over a 5-year period, we report decreased utilization of hospital services associated with decreased morbidity. Our analyses show that this trend in decreased hospital costs correlates with increased utilization of HAART. During the same period, a corresponding increase in outpatient and pharmacy costs is reported, again reflecting administration of HAART in the outpatient setting. We believe these results have important consequences for planning of health care utilization for those who provide care for HIV-infected persons. The use of HAART in our clinic has resulted in better clinical and economic outcomes.

Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy.

The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia ¿PCP, esophageal candidiasis, and disseminated Mycobacterium avium complex ¿MAC disease) were more pronounced in 1996-1998, during which time highly active antiretroviral therapy (HAART) was introduced into medical care. Those OIs that continue to occur do so at low CD4+ T lymphocyte counts, and persons whose CD4+ counts have increased in response to HAART are at low risk for OIs, a circumstance that suggests a high degree of immune reconstitution associated with HAART. PCP, the most common serious OI, continues to occur primarily in persons not previously receiving medical care. The most profound effect on survival of patients with AIDS is conferred by HAART, but specific OI prevention measures (prophylaxis against PCP and MAC and vaccination against Streptococcus pneumoniae) are associated with a survival benefit, even when they coincide with the administration of HAART. Continued monitoring of incidence trends and detection of new syndromes associated with HAART are important priorities in the HAART era.

Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes.

Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV-1 infection without clear understanding of its immunological effects. Here, we demonstrate that early use of HAART during primary infection preserves HIV-specific CD8(+) T cells physically and functionally while HIV-specific T cell help is sustained. We also show that even transient administration of HAART at seroconversion can preserve HIV-specific immunity. In contrast, delayed initiation of HAART is associated with a progressive loss of HIV-specific CD8(+) T cells and absent HIV-specific T cell help. These results imply that HIV-specific T help is damaged during primary HIV-1 infection. Early drug treatment, which preserves this immunity, also preserves HIV-specific CD8(+) T cells. These results have implications for understanding the early pathogenesis of HIV-1 infection and suggest that acute HIV infection should be treated aggressively and as early as possible.

Continuous Quality Improvement Project: Decreasing the Potential for the Development in the Inpatient Setting of Drug Resistance by Improving Nursing Practice for HAART Administration

HIV/AIDS patients' dissatisfaction with highly active antiretroviral therapy (HAART) medication administration in the inpatient setting was the impetus for a continuous quality improvement (CQI) project. The purpose of the CQI project was to initiate a change in nursing practice for HAART medication administration. The goal of the project was to decrease the potential for development of drug resistance in the inpatient setting related to nonadherence with food requirements for drug administration and to incomplete or "missed" doses of prescribed HAART. A secondary goal was to increase the provision of patient education on HAART medications by nurses. The interdisciplinary CQI team found that medication administration in the inpatient setting involved more than nurses simply "passing meds." Inpatient medication administration was a complex process involving a variety of hospital systems, departments, and traditions, all of which had an impact on patient care. The article describes the CQI methodology that was used for the project and how each step of the project was planned and implemented. Specific problems related to administering HAART in the hospital setting are listed as areas for needed nursing research.

Antigen-specific T-lymphocyte proliferative responses during highly active antiretroviral therapy (HAART) of HIV-1 infection

To evaluate functional T-cell recovery during combination therapy with ritonavir, lamivudine (3TC), and zidovudine (ZDV), peripheral blood mononuclear cells (PBMC) were obtained from 4 HIV-1 infected patients (baseline values: 40 403 CD4+ T-cells/microl; 4.6-6.4 log HIV-1 RNA copies/ml) before HAART administration (week -1) and after 5, 20, and 37 weeks of treatment on average. In vitro lymphoproliferative responses (LPR) to C. albicans, tetanus toxoid, and M. tuberculosis protein purified derivative (PPD), as recall antigens (Ag), and to recombinant HIV-1 Gag-p24 and p17 were measured by 3H-Thymidine incorporation. LPR to recall Ag, almost undetectable before therapy, appeared in all four patients during HAART soon after maximal load reduction was achieved. LPR to Gag-p17, but not to p24, became also detectable in three patients, even though remaining weak. In conclusion, improved T-lymphocyte function during HAART was achieved probably mostly as a result of lower virus inhibitory factors and cytokines.