Search

The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral therapy (HAART). The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20 %) was used for data interpretation. At baseline, 9/12 subjects (75.0 %) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5–X4, one X4–R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism. [ABSTRACT FROM AUTHOR]

Predictors of non-response were investigated in a 15-year follow-up (1981-1996) of 3,481 individuals in a probability sample from the household population of East Baltimore. Demographics (age, sex, race, education, marital status, and unemployment), household factors (living arrangements, household income, household size, and number of children), cultural variables (ancestral ethnicity and foreign language), social variables (social support and networks, committing felony, carrying a weapon, using an alias, and wandering), health factors (physical illness, health insurance, medical assistance, Medicare, receiving disability benefits, social security, and welfare), interviewer's observation, and psychopathologic variables (mental disorders, suicide behavior, comorbidity, and drug use) were collected at baseline in 1981 and in 1982, then linked to follow-up data between 1993 and 1996. A tracing process involving mail, phone, criss-cross directories, motor vehicle administration records, a commercial credit bureau, the state criminal justice system, hospital records, the US National Death Index, and field tracing were used to locate the original sample. A total of 3,066 respondents of the original sample (88.1%) were traced. Non-response was categorized into Sample Mortality (that part of the original sample that died during follow-up), Sample Loss (that part of the original sample that survived but could not be found) and Refusal (that part of the original sample that survived and was found but refused to participate). Stratified analysis and adjusted multiple logistic regression modeling found sample mortality and sample loss were strongly influenced by individual and household variables and by psychopathology. Sample mortality was influenced by specific mental disorders or conditions as mania, drug abuse/dependency, antisocial personality, cognitive impairment, alcohol abuse/dependency, phobia, drug use (except PCP), and comorbidity. Household factors protective against mortality include higher household income, not living as extended members in a married couple family, and living with children in the household. Persons who were unemployed, widowed or single, without high school education, male, and 65 years of age or older were more likely to die. Sample loss was influenced by cognitive impairment, antisocial personality, and cocaine use. Household factors linked to sample loss include living in female-headed families, or non-family households, and living alone. Young nonwhite, divorced/separated, without high school education, and unemployed were also harder to find. Refusal was associated with being white, with incomplete elementary education, living as a spouse in traditional married couple families, or as a child in female-headed families. Psychopathology did not influence refusal. [ABSTRACT FROM AUTHOR]