Andrew R. Moss

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

Transmission of Tuberculosis in New York City -- An Analysis by DNA Fingerprinting and Conventional Epidemiologic Methods

BACKGROUND The incidence of tuberculosis and drug resistance is increasing in the United States, but it is not clear how much of the increase is due to reactivation of latent infection and how much to recent transmission. METHODS We performed DNA fingerprinting using restriction-fragment-length polymorphism (RFLP) analysis of at least one isolate from every patient with confirmed tuberculosis at a major hospital in the Bronx, New York, from December 1, 1989, through December 31, 1992. Medical records and census-tract data were reviewed for relevant clinical, social, and demographic data. RESULTS Of 130 patients with tuberculosis, 104 adults (80 percent) had complete medical records and isolates whose DNA fingerprints could be evaluated. Isolates from 65 patients (62.5 percent) had unique RFLP patterns, whereas isolates from 39 patients (37.5 percent) had RFLP patterns that were identical to those of an isolate from at least 1 other study patient; the isolates in the latter group were classified into 12 clusters. Patients whose isolates were included in one of the clusters were inferred to have recently transmitted disease. Independent risk factors for having a clustered isolate included seropositivity for the human immunodeficiency virus (HIV) (odds ratio for Hispanic patients, 4.31; P = 0.02; for non-Hispanic patients, 3.12; P = 0.07), Hispanic ethnicity combined with HIV seronegativity (odds ratio, 5.13; P = 0.05), infection with drug-resistant tuberculosis (odds ratio, 4.52; P = 0.005), and younger age (odds ratio, 1.59; P = 0.02). Residence in sections of the Bronx with a median household income below

Seropositivity for HIV and the development of AIDS or AIDS related condition: three year follow up of the San Francisco General Hospital cohort

20,000 was also associated with having a clustered isolate (odds ratio, 3.22; P = 0.04). CONCLUSIONS In the inner-city community we studied, recently transmitted tuberculosis accounts for approximately 40 percent of the incident cases and almost two thirds of drug-resistant cases. Recent transmission of tuberculosis, and not only reactivation of latent disease, contributes substantially to the increase in tuberculosis.

The intrinsic transmission dynamics of tuberculosis epidemics.

The three year actuarial progression rate to the acquired immune deficiency syndrome (AIDS) in a cohort of men in San Francisco who were seropositive for the human immuno-deficiency virus (HIV) was 22%. An additional 26 (19%) developed AIDS related conditions. β2 Microglobulin concentration, packed cell volume, HIV p24 antigenaemia, and the proportion and number of T4 lymphocytes each independently predicted progression to AIDS. β2 Microglobulin was the most powerful predictor. The 111 subjects tested who were normal by all predictors (40%) had a three year progression rate of 7%, and the 68 subjects who were abnormal by two or more predictors (24%) had a progression rate of 57%. Two thirds of all men who progressed to AIDS were in the last group. The median T4 lymphocyte count in subjects who did not progress to AIDS fell from 626 × 106 to 327 × 106/1. HIV p24 antigenaemia developed in 7% of the subjects per year. The proportion who were abnormal by two or more predictive variables rose to 41%. At three years an estimated two thirds of the seropositive subjects showed clinical AIDS, an AIDS related condition, or laboratory results that were highly predictive of AIDS. It is concluded from the observed rates and the distribution of predictive variables at three years that half of the men who were seropositive for HIV will develop AIDS by six years after the start of the study, and three quarters will develop AIDS or an AIDS related condition.

Hepatitis C Virus Seroconversion among Young Injection Drug Users: Relationships and Risks

In developed countries the major tuberculosis epidemics declined long before the disease became curable in the 1940s. We present a theoretical framework for assessing the intrinsic transmission dynamics of tuberculosis. We demonstrate that it takes one to several hundred years for a tuberculosis epidemic to rise, fall and reach a stable endemic level. Our results suggest that some of the decline of tuberculosis is simply due to the natural behaviour of an epidemic. Although other factors must also have contributed to the decline, these Causal factors were constrained to operate within the slow response time dictated by the intrinsic dynamics.

Emergency department use among the homeless and marginally housed: Results from a community-based study

The present study examined reasons for the high incidence of hepatitis C virus (HCV) infection among young injection drug users (IDUs). IDUs <30 years old who tested negative for HCV antibody were enrolled in a prospective cohort. Risk factors for seroconversion were examined using time-dependent regression analyses: 48 of 195 IDUs seroconverted to HCV, for an incidence rate of 25.1/100 person-years (95% confidence interval, 18.7-32.9/100 person-years). Independent risk factors included sharing needles with an HCV-infected sex partner (borderline statistical significance, P=.11) or a person who was not a sex partner, sharing nonsterile drug-preparation equipment, pooling money with another IDU to buy drugs, and exchanging sex for money. Ubiquitous behaviors among young IDUs, such as the forming of injecting or sexual partnerships and consequent sharing of needles and drug preparation equipment, are risk factors for HCV. Interventions to reduce HCV transmission must recognize the importance of relationships on injecting risk.

Gender differences in sexual and injection risk behavior among active young injection drug users in San Francisco (the UFO Study).

OBJECTIVES This study examined factors associated with emergency department use among homeless and marginally housed persons. METHODS Interviews were conducted with 2578 homeless and marginally housed persons, and factors associated with different patterns of emergency department use were assessed in multivariate models. RESULTS Findings showed that 40.4% of respondents had 1 or more emergency department encounters in the previous year; 7.9% exhibited high rates of use (more than 3 visits) and accounted for 54.5% of all visits. Factors associated with high use rates included less stable housing, victimization, arrests, physical and mental illness, and substance abuse. Predisposing and need factors appeared to drive emergency department use. CONCLUSIONS Efforts to reduce emergency department use among the homeless should be targeted toward addressing underlying risk factors among those exhibiting high rates of use.

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

Female injection drug users (IDUs) represent a large proportion of persons infected with HIV in the United States, and women who inject drugs have a high incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) injection. Therefore, it is important to understand the role of gender in injection risk behavior and the transmission of blood-borne virus. In 2000–2002, 844 young (<30 years old) IDUs were surveyed in San Francisco. We compared self-reported risk behavior between 584 males and 260 female participants from cross-sectional baseline data. We used logistic regression to determine whether demographic, structural, and relationship variables explained increased needle borrowing, drug preparation equipment sharing, and being injected by another IDU among females compared to males. Females were significantly younger than males and were more likely to engage in needle borrowing, ancillary equipment sharing, and being injected by someone else. Females were more likely than males to report recent sexual intercourse and to have IDU sex partners. Females and males were not different with respect to education, race/ethnicity, or housing status. In logistic regression models for borrowing a used needle and sharing drug preparation equipment, increased risk in females was explained by having an injection partner who was also a sexual partner. Injecting risk was greater in the young female compared to male IDUs despite equivalent frequency of injecting. Overlapping sexual and injection partnerships were a key factor in explaining increased injection risk in females. Females were more likely to be injected by another IDU even after adjusting for years injecting, being in a relationship with another IDU, and other potential confounders. Interventions to reduce sexual and injection practices that put women at risk of contracting hepatitis and HIV are needed.

The prevalence of oral lesions in HIV-infected homosexual and bisexual men : three San Francisco epidemiological cohorts

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.