Treatment simplification in HIV-infected adults as a strategy to prevent toxicity, improve adherence, quality of life and decrease healthcare costs

Since the advent of highly active antiretroviral therapy (HAART), the treatment of human immunodeficiency virus (HIV) infection has become more potent and better tolerated. While the current treatment regimens still have limitations, they are more effective, more convenient, and less toxic than regimens used in the early HAART era, and new agents, formulations and strategies continue to be developed. Simplification of therapy is an option for many patients currently being treated with antiretroviral therapy (ART). The main goals are to reduce pill burden, improve quality of life and enhance medication adherence, while minimizing short- and long-term toxicities, reducing the risk of virologic failure and maximizing cost-effectiveness. ART simplification strategies that are currently used or are under study include the use of once-daily regimens, less toxic drugs, fixed-dose coformulations and induction-maintenance approaches. Improved adherence and persistence have been observed with the adoption of some of these strategies. The role of regimen simplification has implications not only for individual patients, but also for health care policy. With increased interest in ART regimen simplification, it is critical to study not only implications for individual tolerability, toxicity, adherence, persistence and virologic efficacy, but also cost, scalability, and potential for dissemination and implementation, such that limited human and financial resources are optimally allocated for maximal efficiency, coverage and sustainability of global HIV/AIDS treatment

Clinical inertia in the management of low-density lipoprotein abnormalities in an HIV clinic

A retrospective cohort study evaluating the frequency of and factors related to clinical inertia in low-density lipoprotein (LDL) management was performed. Subjects were 90 patients that were not meeting National Cholesterol Education Program Adult Treatment Panel III LDL goals at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic between 1 August 2004 and 1 August 2005. Clinical inertia was observed in 44% of cases. Patients with higher baseline LDL levels were less likely to experience inertia, whereas women and those in the highest coronary heart disease risk category were more likely to be affected

Nucleoside reverse-transcriptase inhibitor dosing errors in an outpatient HIV clinic in the electronic medical record era

Information on antiretroviral dosing errors among health care providers for outpatient human immunodeficiency virus (HIV)-infected patients is lacking. We evaluated factors associated with nucleoside reverse-transcriptase inhibitor dosing errors in a university-based HIV clinic using an electronic medical record. Overall, older age, minority race or ethnicity, and didanosine use were related to such errors. Impaired renal function was more common in older patients and racial or ethnic minorities and, in conjunction with fixed-dose combination drugs, contributed to the higher rates of errors in nucleoside reverse-transcriptase inhibitor dosing. Understanding the factors related to nucleoside reverse-transcriptase inhibitor dosing errors is an important step in the building of preventive tools

The effect of antiretroviral therapy on all-cause mortality, generalized to persons diagnosed with HIV in the USA, 2009–11

Background: Although antiretroviral therapy (ART) is known to be protective against HIV-related mortality, the expected magnitude of effect is unclear because existing estimates of the effect of ART may not directly generalize to recently HIV-diagnosed persons

Generalizing Evidence from Randomized Trials using Inverse Probability of Sampling Weights

Results obtained in randomized trials may not easily generalize to target populations. Whereas in randomized trials the treatment assignment mechanism is known, the sampling mechanism by which individuals are selected to participate in the trial is typically not known and assuming random sampling from the target population is often dubious. We consider an inverse probability of sampling weighted (IPSW) estimator for generalizing trial results to a target population. The IPSW estimator is shown to be consistent and asymptotically normal. A consistent sandwich-type variance estimator is derived and simulation results are presented comparing the IPSW estimator to a previously proposed stratified estimator. The methods are then utilized to generalize results from two randomized trials of HIV treatment to all people living with HIV in the US

An Illustration of Inverse Probability Weighting to Estimate Policy-Relevant Causal Effects

Traditional epidemiologic approaches allow us to compare counterfactual outcomes under 2 exposure distributions, usually 100% exposed and 100% unexposed. However, to estimate the population health effect of a proposed intervention, one may wish to compare factual outcomes under the observed exposure distribution to counterfactual outcomes under the exposure distribution produced by an intervention. Here, we used inverse probability weights to compare the 5-year mortality risk under observed antiretroviral therapy treatment plans to the 5-year mortality risk that would had been observed under an intervention in which all patients initiated therapy immediately upon entry into care among patients positive for human immunodeficiency virus in the US Centers for AIDS Research Network of Integrated Clinical Systems multisite cohort study between 1998 and 2013. Therapy-naïve patients (n = 14,700) were followed from entry into care until death, loss to follow-up, or censoring at 5 years or on December 31, 2013. The 5-year cumulative incidence of mortality was 11.65% under observed treatment plans and 10.10% under the intervention, yielding a risk difference of −1.57% (95% confidence interval: −3.08, −0.06). Comparing outcomes under the intervention with outcomes under observed treatment plans provides meaningful information about the potential consequences of new US guidelines to treat all patients with human immunodeficiency virus regardless of CD4 cell count under actual clinical conditions

Failure to establish HIV care: characterizing the no show phenomenon

It is estimated that up to one-third of persons with known human immunodeficiency virus (HIV) infection in the United States are not engaged in care. We evaluated factors associated with patients\u27 failure to establish outpatient HIV care at our clinic and found that females, racial minorities, and patients lacking private health insurance were more likely to be no shows. At the clinic level, longer waiting time from the call to schedule a new patient visit to the appointment date was associated with failure to establish care. Because increased numbers of patients will be in need of outpatient HIV care as a result of recent Centers for Disease Control and Prevention guidelines advocating routine HIV testing, it is imperative that strategies to improve access are developed to overcome the no show phenomenon

Comparative efficacy versus effectiveness of initial antiretroviral therapy in clinical trials versus routine care

BACKGROUND: The applicability of clinical trial findings (efficacy) to the routine care setting (effectiveness) may be limited because of study eligibility criteria and volunteer bias. Although well-chronicled in many conditions, the efficacy versus effectiveness of antiretroviral therapy (ART) remains understudied. METHODS: A retrospective study of the University of Alabama at Birmingham 1917 Clinic Cohort evaluated ART-naive patients who started ART from 1 January 2000 through 31 December 2006. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virological failure (virological failure was defined as a viral load \u3e50 copies/mL) and change from baseline CD4+ cell count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes. RESULTS: Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials, and 449 (79%) received ART via routine care. ART receipt through routine care was not associated with viral failure at either 6 months (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.54-1.86) or 12 months (OR, 1.56; 95% CI, 0.80-3.05) in primary analyses. No statistically significant differences in CD4+ cell count responses at 6 and 12 months were observed. CONCLUSIONS: Although marked differences in efficacy versus effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients who initiated antiretroviral therapy for human immunodeficiency virus infection