Effect of directly observed antiretroviral therapy compared to self-administered antiretroviral therapy on adherence and virological outcomes among HIV-infected prisoners: a randomized controlled pilot study.

The effect of directly observed therapy (DOT) versus self-administered therapy (SAT) on antiretroviral (ART) adherence and virological outcomes in prison has never been assessed in a randomized, controlled trial. Prisoners were randomized to receive ART by DOT or SAT. The primary outcome was medication adherence [percent of ART doses measured by the medication event monitoring system (MEMS) and pill counts] at the end of 24 weeks.

HIV-1 protease function and structure studies with the simplicial neighborhood analysis of protein packing method.

The Simplicial Neighborhood Analysis of Protein Packing (SNAPP) method was used to predict the effect of mutagenesis on the enzymatic activity of the HIV-1 protease (HIVP). SNAPP relies on a four-body statistical scoring function derived from the analysis of spatially nearest neighbor residue compositional preferences in a diverse and representative subset of protein structures from the Protein Data Bank. The method was applied to the analysis of HIVP mutants with residue substitutions in the hydrophobic core as well as at the interface between the two protease monomers.

A comprehensive evaluation of survey questions for adherence to antiretroviral medications and exploratory analyses for identifying optimal sets of survey questions.

Although many methods for assessing adherence have been developed, most are not feasible for busy clinical settings. Using patients from the Adherence and Efficacy of Protease inhibitor Therapy (ADEPT) study (1998-2000), we systematically evaluated the relationship between psychosocial, environmental, clinical, and other factors with adherence to create composite variables (CVs) that are efficient with high sensitivity for detecting nonadherence and great potential for busy clinics. Eligible patients were protease inhibitor naïve or started a regimen within 3 months from baseline.

A practical method to calibrate self-reported adherence to antiretroviral therapy.

Objective: Self-report of antiretroviral medications adherence is inexpensive and simple to use in clinical settings but grossly overestimates adherence. We investigated methods to calibrate patients' self-reported adherence to match objectively measured adherence more closely for the purpose of developing a practical and more accurate self-reported adherence measure.

Design: Longitudinal cohort design.

A pilot study of health beliefs and attitudes concerning measures of antiretroviral adherence among prisoners receiving directly observed antiretroviral therapy.

High level adherence to antiretroviral therapy (ART) is required to achieve and maintain suppression of HIV replication. Although directly observed therapy (DOT) has been suggested as an intervention to improve adherence, there is a paucity of data describing the attitudes and beliefs regarding DOT for ART among HIV-infected individuals. This study was designed to evaluate the acceptability and psychometric properties of a survey instrument for use in assessing barriers and facilitators of adherence to ART DOT in prison.

HIV and incarceration: dual epidemics.

As a result of changes in the epidemiology of the HIV epidemic and in criminal justice policies over the past 2 decades, HIV infection in the United States has become concentrated in prisons and jails. The widespread incarceration of persons with or at risk for HIV infection has important public health ramifications, including but not limited to the intraprison spread of the virus. Incarceration, particularly of large numbers of men, can be socially disruptive and , in communities where incarceration is prevalent, can facilitate the spread of HIV infection.

Repeated measures analyses of dose timing of antiretroviral medication and its relationship to HIV virologic outcomes.

Medication adherence is a critical predictor of the effectiveness of antiretroviral medications in the treatment of HIV/AIDS. Studies of adherence, however, have focused primarily on the per cent of prescribed doses taken (per cent adherence). In the Adherence and Efficacy of Protease Inhibitor Therapy study, we collected detailed adherence data including dose timing information as well as data regarding patients' virologic responses.

Men who have sex with men and women: a unique risk group for HIV transmission on North Carolina College campuses.

Objective: To better understand the role that men who have sex with men and women (MSM/W) play in the spread of HIV in young adults in North Carolina, we determined the prevalence of MSM/W among newly diagnosed HIV-infected men, compared social and behavioral characteristics of this group with MSM and MSW, and examined the sexual networks associated with HIV-infected college students among these groups.

Methods: We reviewed state HIV surveillance records for all new diagnoses of HIV in males 18 to 30 years living in North Carolina between January 1, 2000, and December 31, 2004.

Results: Of 1,105 records available for review, 15% were MSM/W and 13% were college students.

Repeated measures longitudinal analyses of HIV virologic response as a function of percent adherence, dose timing, genotypic sensitivity, and other factors.

Background: Adherence to antiretroviral medications is critical to achieving HIV viral suppression. Studies have been limited to cross-sectional analyses using measures that reflect only the percentage of prescribed doses taken (percent adherence), however. The contribution of dose timing and other factors to achieving virologic suppression has received less scrutiny.

Sexual behaviours of HIV-seropositive men and women following release from prison.

Twenty-five percent of the US HIV-infected population is released from a prison or jail each year. As the extent of risky sexual behaviours after prison release is largely unknown, we interviewed a cohort (n = 64) of HIV-infected, recently released (mean 45 days, SD 28) prisoners about their current sexual risk behaviours. Almost half (47%, n = 64) of the released prisoners reported sexual activity after release, mostly with regular partners.

HIV and stigma: analysis and research program.

Despite advances in our understanding of HIV transmission and optimal treatment of people with HIV infection, stigmatizing attitudes are a significant barrier to HIV prevention and treatment. Several studies demonstrate that stigma directed towards people with HIV infection presents an obstacle to getting tested for HIV, obtaining optimal HIV care, and engaging in safe sex practices. We review the literature on individual and societal factors associated with HIV-associated stigma and propose a framework for intervention design.

Processing sites in the human immunodeficiency virus type 1 (HIV-1) Gag-Pro-Pol precursor are cleaved by the viral protease at different rates.

We have examined the kinetics of processing of the HIV-1 Gag-Pro-Pol precursor in an in vitro assay with mature protease added in trans. The processing sites were cleaved at different rates to produce distinct intermediates. The initial cleavage occurred at the p2/NC site.

Ordered processing of the human immunodeficiency virus type 1 GagPol precursor is influenced by the context of the embedded viral protease.

Ordered and accurate processing of the human immunodeficiency virus type 1 (HIV-1) GagPol polyprotein precursor by a virally encoded protease is an indispensable step in the appropriate assembly of infectious viral particles. The HIV-1 protease (PR) is a 99-amino-acid enzyme that is translated as part of the GagPol precursor. Previously, we have demonstrated that the initial events in precursor processing are accomplished by the PR domain within GagPol in cis, before it is released from the polyprotein.

The unexpected movement of the HIV epidemic in the Southeastern United States: transmission among college students.

Background: Approximately 16 million people are enrolled in institutions of higher learning in the United States. However, college students have not been perceived as at high risk for HIV infection. In early 2003, acute HIV infection was diagnosed in 2 men attending college in North Carolina.

Effect of release from prison and re-incarceration on the viral loads of HIV-infected individuals.

Objectives: The purpose of this study was to determine the effect of release from prison and subsequent re-incarceration on the viral loads of HIV-infected individuals receiving highly active antiretroviral therapy (HAART).

Methods: Fifteen re-incarcerated HIV-infected prisoners on HAART were identified from a retrospective cohort of HIV-infected prison inmates released from January 1, 1997, to August 31, 1999. The re-incarcerated prisoners were matched (1:2) to 30 HIV-infected incarcerated prisoners on HAART who remained incarcerated during the re-incarcerated participants' release time period.

Availability of and access to medical services among HIV-infected inmates incarcerated in North Carolina county jails.

This study assessed human immunodeficiency virus (HIV)-related services in county jails and staff perceptions of HIV-infected inmates and their care. A statewide telephone questionnaire was administered to detention officers and health care workers providing medical services in North Carolina jails. Eighty-five percent of participating facilities employed one or more on-site medical personnel, including physicians (51%), physician assistants (14%), and nurses (71%).

Initial cleavage of the human immunodeficiency virus type 1 GagPol precursor by its activated protease occurs by an intramolecular mechanism.

Processing of the GagPol polyprotein precursor of human immunodeficiency virus type 1 (HIV-1) is a critical step in viral assembly and replication. The HIV-1 protease (PR) is translated as part of GagPol and is both necessary and sufficient for precursor processing. The PR is active only as a dimer; enzyme activation is initiated when the PR domains in two GagPol precursors dimerize.

Predictors of repeat testing and HIV seroconversion in a sexually transmitted disease clinic population.

Objective: This study assessed the extent of and characteristics associated with repeat HIV testing in persons presenting to a sexually transmitted disease (STD) clinic.

Methods: The study population included all 101 newly diagnosed HIV-infected subjects and 411 matched HIV-uninfected subjects identified over a 5-year period in a publicly funded STD clinic in the southeastern United States.

Results: Of the 508 subjects (99%) with available records, 160 (32%) had tested previously.

No evidence of an association between transient HIV viremia ("Blips") and lower adherence to the antiretroviral medication regimen.

Background: Transient human immunodeficiency virus (HIV) viremia, a common phenomenon among patients taking antiretroviral therapy, is often attributed to lapses in adherence to the medication regimen. We investigated this relationship in a prospective observational cohort of 128 patients initiating a new regimen.

Methods: A case of transient viremia was defined as an HIV RNA level of 40-1000 copies/mL ("blip") sandwiched between 2 months of HIV RNA levels <40 copies/mL ("pre" and "post").

Failure to return for HIV posttest counseling in an STD clinic population.

This study assessed the extent of and characteristics associated with FTR for HIV posttest counseling in persons undergoing an HIV test during their visit to a sexually transmitted disease (STD) clinic. The study population included all 101 newly diagnosed HIV-infected subjects and 411 matched HIV-uninfected subjects, identified over a 5-year period in a publicly funded STD clinic in the southeastern United States. Overall, 55% of subjects failed to return for their test results.

Adherence to directly observed antiretroviral therapy among human immunodeficiency virus-infected prison inmates.

Directly observed therapy (DOT) for human immunodeficiency virus (HIV) infection is commonly used in correctional settings; however, the efficacy of DOT for treating HIV infection has not been determined. We prospectively assessed adherence to antiretroviral therapy regimens among 31 HIV-infected prison inmates who were receiving >or=1 antiretrovirals via DOT. Adherence was measured by self-report, pill count, electronic monitoring caps, and, for DOT only, medication administration records.

Mutagenesis of the dimer interface residues of tethered and untethered HIV-1 protease result in differential activity and suggest multiple mechanisms of compensation.

As is the case for all retroviruses, the protease of HIV-1 is only functional as a homodimer; dimerization of two protease monomers results in the formation of the enzyme active site. This dimer structure is supported primarily by interactions between the first four amino-terminal and the last four carboxy-terminal amino acids. These eight amino acids form a beta-sheet in which hydrophobic residues are oriented towards the core of the molecule and polar residues are directed towards the solvent.

Knowledge of antiretroviral regimen dosing and adherence: a longitudinal study.

In a cohort of 128 human immunodeficiency virus-infected patients, we found that patients' knowledge of antiretroviral dosing was suboptimal at regimen initiation but improved with time. Poor medication knowledge 8 weeks after regimen initiation was associated with lower adherence and with a lower level of literacy in a multivariate model (P=.03).

The dimer interfaces of protease and extra-protease domains influence the activation of protease and the specificity of GagPol cleavage.

Activation of the human immunodeficiency virus type 1 (HIV-1) protease is an essential step in viral replication. As is the case for all retroviral proteases, enzyme activation requires the formation of protease homodimers. However, little is known about the mechanisms by which retroviral proteases become active within their precursors.

Impact of antiretroviral regimen switches on adherence.

Purpose: An understanding of the situations in which adherence lapses occur is critical to the design of effective interventions to enhance adherence. We investigated whether a switch in antiretroviral medications affected adherence by examining a prospective observational cohort of 128 patients who began a new antiretroviral regimen.

Method: Adherence was measured using electronic devices, pill counts, and self-reports, which were combined into a composite adherence measure and expressed as the proportion of prescribed medication taken.