We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg. These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach.

Treatment with protease inhibitors is associated with peripheral insulin resistance, leading to impaired or diabetic oral glucose tolerance in some of the patients, and with hyperlipidaemia. Overall, there is a large variation in the severity and clinical presentation of protease inhibitor-associated metabolic side-effects.

The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression, significant improvements in lipid abnormalities and enhanced ease of dosing.

A drastic decrease in incidence has been observed for most human immunodeficiency virus (HIV)-related opportunistic manifestations after use of highly active antiretroviral therapy (HAART). We assessed the trend of incidence of central nervous system (CNS) diseases in a prospective multicenter observational study involving 9,803 patients across Europe in the period 1994 to 2002 and analyzed patient and treatment variables associated with these conditions. Overall, 568 patients (5.8%) received a diagnosis of a new CNS disease. Incidence decreased significantly from 5.9 per 100 person-year in 1994 to 0.5 in 2002. Overall, the decrease was 40% per calendar year, and it was similar to that of non-CNS diseases and less evident after year 1998. In multivariable models, low CD4 cell count and high plasma viral load, but not HAART or calendar year, were significantly associated with risk to develop CNS disease, indicating that the effect of HAART was likely mediated by both improved immunological conditions and inhibition of viral replication. In contrast, use of nucleoside reverse transcriptase inhibitors, irrespective of use of protease inhibitors or non-nucleoside reverse transcriptase inhibitors, appeared to protect specifically against acquired immunodeficiency disease syndrome dementia complex, suggesting that, in this condition, therapy might have a direct, additive effect in the CNS.

To determine the prevalence, incidence, and types of lung diseases that occur in association with HIV infection, 1,353 subjects, including HIV-seropositive homosexual men, injection drug users, female sexual partners of HIV-positive men, and HIV-seronegative control subjects from the first two transmission categories were evaluated prospectively in a multicenter study. Patients with AIDS at the time of initial evaluation were excluded. One thousand two-hundred ninety-four subjects who had no AIDS-defining diagnosis within 3 mo of enrollment had measurements of FVC, FEV1 and DLCO at the time of enrollment. As a group, all subjects had mean values of FVC and FEV1 close to 100% predicted. Those with CD4 counts below 200/mm3 had slightly reduced DLCO compared with the others. Subjects with a history of HIV-associated symptoms (thrush, weight loss, herpes zoster) also had a reduced DLCO compared with those without symptoms. Injection drug users had reduced FVC, FEV1 and DLCO compared with homosexual men and female sexual partners of HIV-infected men, with DLCO more substantially reduced. Part of the reduction in DLCO in drug users was attributable to factors other than HIV infection, especially cigarette smoking and race. Using predicted values that take cigarette smoking into account, the prevalence of abnormality in DLCO was higher among injection drug users (33.3%) than among homosexual men (11.2%) and female sexual partners (12.7%). These results show that advanced HIV infection, characterized by CD4 count < 200/mm3 or HIV-associated symptoms, and factors unrelated to HIV infection, including race, cigarette smoking, and injection drug use, are all associated with reductions in DLCO measurements.