Edwin D. Charlebois

Adherence to protease inhibitors, Hiv-1 viral load, and development of drug resistance in an indigent population

ObjectiveTo examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy. Design and settingA cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels. ParticipantsThirty-four HIV-infected people with a median of 12 months of PI therapy. Main outcomesAdherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance. ResultsMedian adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirty-eight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36–65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P < 0.03). ConclusionA substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.

Non-adherence to highly active antiretroviral therapy predicts progression to AIDS

The introduction of highly active antiretroviral therapy (HAART) has produced a dramatic reduction in mortality among HIV-infected individuals [1–4]. Whereas the level of adherence to HAART is closely associated with suppression of the HIV viral load in plasma [5–14], a relationship between adherenc

Multiple Validated Measures of Adherence Indicate High Levels of Adherence to Generic Hiv Antiretroviral Therapy in a Resource-limited Setting

Background:There are no validated measures of adherence to HIV antiretroviral therapy in resource-poor settings. Such measures are essential to understand the unique barriers to adherence as access to HIV antiretroviral therapy expands. Methods:We assessed correspondence between multiple measures of adherence and viral load suppression in 34 patients purchasing generic Triomune antiretroviral therapy (coformulated stavudine, lamivudine, and nevirapine; CIPLA, Ltd., Mumbai, India) in Kampala, Uganda. Measures included 3-day patient self-report, 30-day visual analog scale, electronic medication monitoring, and unannounced home pill count. HIV-1 load was determined at baseline and 12 weeks. Results:Mean adherence was 91%–94% by all measures. Seventy-six percent of subjects had a viral load of <400 copies/mL at 12 weeks. All measures were closely correlated with each other (R = 0.77–0.89). Each measure was also significantly associated with 12-week HIV load. There was no significant difference between patient-reported and objective measures of adherence. Conclusions:This sample of patients purchasing generic HIV antiretroviral therapy has among the highest measured adherence reported to date. Patient-reported measures were closely associated with objective measures. The relative ease of administration of the 30-day visual analog scale suggests that this may be the preferred method to assess adherence in resource-poor settings.

High levels of adherence do not prevent accumulation of HIV drug resistance mutations.

Objectives: To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence. Methods: Adherence was measured with unannounced pill counts performed at the participants usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2. Results: High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92–100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79–100%). Conclusion: Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.

Measuring Adherence to Antiretroviral Therapy in a Diverse Population Using a Visual Analogue Scale

Abstract Purpose: To examine the performance of an instrument to assess adherence based on a visual analogue scale, compared to an instrument based on 3-day recall, using unannounced pill counts in the place of residence as the gold standard. Method: We prospectively assessed adherence to antiretroviral therapy in 84 marginally housed indigent HIV-infected patients who were receiving stable antiretroviral therapy in San Francisco, California, with three adherence assessments over no more than 4 months. Results: Mean adherence using the visual analogue scale, 3-day recall, and unannounced pill count methods were 82.5%, 84.2%, and 75.9%, respectively. The correlation between visual analogue scale and unannounced pill count was high (r = 0.76) and was not statistically different from that between 3-day recall and unannounced pill count (r = 0.71; p = .52). Both methods were also similarly inversely correlated with HIV viral load (r = -0.49 and -0.34, respectively; p = .22 for the difference in the correlations). The visual analogue scale correlation with unannounced pill count was stable over time and remained high in all subpopulations examined. Conclusion: A visual analogue scale to assess adherence was performed as well as a more complicated 3-day recall instrument in this diverse population. Given its simplicity, the visual analogue scale adherence instrument will be useful in research and may be useful in routine patient care.

Population-based community prevalence of methicillin-resistant Staphylococcus aureus in the urban poor of San Francisco

The study objective was to determine the prevalence and risk factors for nasal colonization with Staphylococcus aureus and methicillin resistance among the urban poor and to compare antibiotic resistance and genetic similarity to concurrently collected clinical isolates of methicillin-resistant S. aureus (MRSA). A population-based community sample of 833 homeless and marginally housed adults were cultured and compared with 363 clinical isolates of MRSA; 22.8% of the urban poor were colonized with S. aureus. Of S. aureus isolates, 12.0% were methicillin resistant. Overall prevalence of MRSA was 2.8%. Significant multivariate risk factors for MRSA were injection drug use (odds ratio [OR], 9.7), prior endocarditis (OR, 4.1), and prior hospitalization within 1 year (OR, 2.4). Resistance to antimicrobials other than beta-lactams was uncommon. Only 2 individuals (0.24%) with MRSA had no known risk factors. A total of 22 of 23 community MRSA genotypically matched clinical MRSA isolates, with 15 of 23 isolates identical to MRSA clones endemic among hospitalized patients.

Community-Adapted Methicillin-Resistant Staphylococcus aureus (MRSA): Population Dynamics of an Expanding Community Reservoir of MRSA

To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the community and their population dynamics, we studied the molecular epidemiology of a random sample (n=490) from a collection of 2154 inpatient and outpatient MRSA isolates during a 7-year period in San Francisco. We noted a progressive replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing isolates with type IV SCCmec-bearing isolates, which coincided with >4-fold increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing isolates involved in the increase in methicillin resistance belonged to 4 molecular genotypes. These 4 genotypes were associated predominantly with community-onset disease, rather than hospital- or long-term-care facility-onset disease (76.9% vs. 19.4% vs. 3.7%; P=.0005), suggesting that they are not feral descendants of hospital isolates. The longitudinal results linked the dramatic increase in MRSA infections to an expanding community reservoir of MRSA genotypes with intrinsic community survival advantage.

Provider assessment of adherence to HIV antiretroviral therapy.

Background: Adherence assessment is an essential component of monitoring HIV antiretroviral therapy. Prior studies suggest that medical providers frequently estimate individual patient adherence inaccurately. Objective: We compared provider estimates of nonadherence to antiretroviral therapy with unannounced pill counts and structured patient interviews to determine the accuracy of adherence information obtained by providers and patients. Design, setting, and participants: Comparison of three adherence measures in homeless or marginally housed persons receiving HIV antiretroviral therapy (n = 45) and their providers (n = 35). Measurements: Provider estimate of percentage of pills taken; three successive patient structured reports of number of doses missed in the last 3 days; and three successive unannounced pill counts. Results: 13% (95% confidence interval [CI], 4%‐22%) of patients were not fol lowing their regimen as directed. Provider‐adherence estimate explained only 26% (95% CI, 6%‐47%) of the variation in pill count adherence, whereas patient report explained 72% (95% CI, 52%‐96%). The sensitivity and specificity of provider esti mates of nonadherence, defined as < 80% of pills taken by pill count, were 40% and 85%, respectively. The sensitivity and specificity of patient interview were 72% and 95%, respectively. Conclusions: Provider estimate of adherence was inaccurate whereas structured patient report was more closely related to pill count. Structured assessment over several short intervals may improve accuracy of adherence assessment in clinical practice.

HIV Seroprevalence Among Homeless and Marginally Housed Adults in San Francisco

OBJECTIVES We report HIV seroprevalence and risk factors for urban indigent adults. METHODS A total of 2508 adults from shelters, meal programs, and low-cost hotels received interviews, blood tests, and tuberculosis screening. RESULTS Seroprevalence was 10.5% overall, 29.6% for men reporting sex with men (MSM), 7.7% for non-MSM injection drug users (IDUs), and 5.0% for residual non-MSM/non-IDUs. Risk factors were identified for MSM (sex trade among Whites, non-White race, recent receptive anal sex, syphilis), non-MSM IDUs (syphilis, lower education, prison, syringe sharing, transfusion), and residual subjects (> or = 5 recent sexual partners, female crack users who gave sex for drugs). CONCLUSIONS HIV seroprevalence was 5 times greater for indigent adults than in San Francisco generally. Sexual behavior predicted HIV infection better than drug use, even among IDUs.

Increasing Prevalence of Methicillin-Resistant Staphylococcus aureus Infection in California Jails

Staphylococcus aureus clinical isolates obtained from patients who were inmates of the San Francisco County jail system showed an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) from 29%, in 1997, to 74%, in 2002; 91% of the MRSA isolates carried staphylococcal chromosomal cassette mec (SCCmec) type IV. Pulsed field gel electrophoresis and multilocus sequence typing demonstrated 2 major clonal groups. One of these clonal groups is genetically indistinguishable from the strain responsible for an outbreak of MRSA in the Los Angeles County jail system in 2002.