abacavir and Chronic-Disease

This review will discuss emerging evidence for the possibility that AIDS dementia complex (ADC) has changed in the era of highly active antiretroviral therapy (HAART). The consequences of not considering these possibilities at the patient level and at the level of research are considerable. Data will be discussed that are derived from epidemiological studies, neuropsychological and positron emission tomography studies, as well as analyses from the abacavir ADC trial. These will then be assessed to develop the concept that there are now different forms of ADC: an inactive form, a chronic variety and a 'transformed' variant. Whereas the latter relates to the compounding influence of a number of other processes on ADC, such as hepatitis C, particular discussion will focus upon Alzheimer's disease and whether HIV may lead to Alzheimer-like changes. It is certainly recognized that some of the concepts discussed here are highly speculative.

Topics: Age Factors; AIDS Dementia Complex; Alzheimer Disease; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chronic Disease; Cognition Disorders; Dideoxynucleosides; Humans; RNA, Viral; Severity of Illness Index

A Phase II clinical trial was designed to evaluate the efficacy and tolerability of twice-daily abacavir, amprenavir, and zidovudine (ZDV)/lamivudine (3TC) in HIV-1-infected study subjects naive to protease inhibitors and 3TC. Plasma and cerebrospinal fluid (CSF) HIV-1 RNA levels and T-cell subsets were measured. In all, 27 newly diagnosed and 12 chronically HIV-1-infected study subjects are included in the analysis. Week 48 plasma HIV-1 RNA levels were <500 copies/ml in 100% of study subjects, and <50 copies/ml in 80% of chronically infected and 100% of newly infected study subjects. The mean change in CD4 was (+)150 cells/microl (newly infected, p <.001), and (+)155 cells/microl (chronically infected, p <.001). At Week 48, evidence of cellular activation persisted in both cohorts. A twice-daily regimen of amprenavir, abacavir, and ZDV/3TC affords potent viral suppression and significant increases in total CD4(+) cells in HIV-1--infected study subjects. Patient intolerance may limit the efficacy of this combination.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS Dementia Complex; Anti-HIV Agents; Carbamates; CD4 Lymphocyte Count; Chronic Disease; Dideoxynucleosides; Digestive System; Drug Synergism; Ethnicity; Female; Furans; HIV Infections; HIV-1; Humans; Lamivudine; Lymphocyte Subsets; Male; Pregnancy; Research Design; RNA, Viral; Sulfonamides; Treatment Refusal; Zidovudine

When to start highly active antiretroviral therapy (HAART) in asymptomatic chronically HIV-1-infected subjects with CD4 cell counts of 300 x 10(6)-500 x 10(6)/l is debated extensively. Retrospective analyses of virological and immunological responses following HAART have been evaluated in both blood and lymph nodes according to pre-treatment levels of CD4 cells either above or below 500 x 10(6)/l.. Open-label, observational, non-randomized, prospective study.. Outpatients attending the Centre of Clinical Investigation in Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.. Fifty-four HIV-1-infected antiretroviral-naive subjects with CD4 cell count > or = 250 x 10(6)/l and plasma viraemia > or = 5000 copies/ml who had been treated with HAART for at least 48 weeks. Controls were 49 HIV-negative subjects.. All patients received abacavir, nelfinavir, saquinavir soft gel capsules, and amprenavir in varying combinations for 72 weeks.. The extent of immune reconstitution following HAART in 43 and 11 subjects with either more or fewer than 500 x 10(6) CD4 cells/l at baseline was evaluated in blood and lymph node, and compared with immunological measures observed in 49 HIV-negative controls.. After 48 weeks of therapy, plasma viraemia was suppressed effectively in both groups of patients. Normalization of both CD4 cell count in blood, divided equally between memory and naive cells, and percentage of CD4 cells in lymph nodes occurred in the two groups. Consistently, the net increase over baseline in CD4 cell count and in memory and naive CD4 subsets was greater in patients with fewer than 500 x 10(6) CD4 cells/l at baseline. Recovery of HIV-specific responses was similar in the two groups.. This study suggests that virological and immunological responses are comparable in asymptomatic therapy-naive HIV-1-infected subjects with CD4 cell counts above or below 500 x 10(6)/l.

Topics: Adult; Anti-HIV Agents; Antigens, Fungal; Antigens, Viral; Antiretroviral Therapy, Highly Active; Candida albicans; Carbamates; CD4 Lymphocyte Count; Chronic Disease; Cytomegalovirus; Dideoxynucleosides; Drug Therapy, Combination; Furans; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Nelfinavir; Prospective Studies; Reverse Transcriptase Inhibitors; RNA, Viral; Saquinavir; Simplexvirus; Sulfonamides; T-Lymphocyte Subsets

We report the case of an HIV-infected woman, who presented with chronic and productive cough without sign of hypersensitivity (fever, cutaneous eruption, gastrointestinal disorders), while taking abacavir. All complementary exams being negative, the involvement of abacavir has been suspected. So the drug was stopped leading to a rapid disappearance of cough. It is the first report of chronic cough with abacavir apart of a context of hypersensitivity reaction.

Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Chronic Disease; Cough; Cyclopropanes; Dideoxynucleosides; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Middle Aged; Nelfinavir; Oxazines; Reverse Transcriptase Inhibitors; Rhinitis; Sputum; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination