SUMMARYBackground: A new generation of antipsychotics was introduced over a decade ago for the

The HIV-1 biological phenotype is a practical, binary marker for progression to AIDS, which is independent of decreased CD4+ cell counts and antigenemia. Appearance of SI variants, occurring 2 years before progression to AIDS on the average, is predictive for a significantly increased rate of CD4+ cell decline.

Sumlllal'yTo gain more insight into the role of HIV-l-specific cytotoxic T lymphocytes (CTL) in the pathogenesis of AIDS, we investigated temporal relations between HIV-1 Gag-specific precursor CTL (CTLp), HIV-1 viral load, CD4 + T cell counts, and T cell function. Six HIV-l-infected subjects, who were asymptomatic for more than 8 yr with CD4 + counts >500 ceUs/mm 3, were compared with six subjects who progressed to AIDS within 5 yr after HIV-1 seroconversion. In the long-term asymptomatics, persistent HIV-1 Gag-specific CTL responses and very low numbers of HIV-l-infected CD4 + T cells coincided with normal and stable CD4 + counts and preserved CD3 mAb-induced T cell reactivity for more than 8 yr. In five out of six rapid progressors Gag-specific CTLp were also detected. However, early in infection the number of circulating HIV-l-infected CD4 + T cells increased despite strong and mounting Gag-specific CTL responses. During subsequent clinical progression to AIDS, loss of Gag-specific CTLp coincided with precipitating CD4 + counts and severe deterioration of T cell function. The possible relationships of HIV-1 Gag-specific CTLp to disease progression are discussed.

Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.

The causal relationship between HIVspecific CD4 ؉ T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4 ؉ T cells were analyzed in long-term asymptomatic individuals (LTA; n ‫؍‬ 6) and progressors to AIDS (n ‫؍‬ 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4 ؉ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gagspecific CD4 ؉ T cells producing IL-2 or IFN␥ were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2 ؉ , IFN␥ ؉ , or IL-2 ؉ IFN␥ ؉ CD4 ؉ T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4 ؉ T-cell responses, rather than HIV-specific CD4 ؉ T-cell responses controlling HIV plasma viral load. (Blood.