Expanded Access Program for Maraviroc At Multiple Centers

AEs as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3 = severe: interrupted usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4 = very severe: events that were unacceptable and intolerable or were irreversable or caused imminent danger of death. If same participant had more than 1 occurrence in the same preferred term event category, only the most severe (grade 4) occurrence was taken. Treatment-related = investigator assessment of a reasonable possibility that the investigational product caused or contributed to the AE.

Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3, Severe =events that interrupted participants usual daily activity and traditionally required systemic drug therapy or other treatment.

Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 4, Very Severe = events which were unacceptable and intolerable or were irreversible or caused the participant to be in imminent danger of death.

Treatment-emergent AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C adverse events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 30 days after last dose of study drug.

Treatment-emergent AEs by gender that occurred up to 30 days after the last dose of study medication.

Treatment-emergent AEs by race that occurred up to 30 days after the last dose of study medication.

Treatment-emergent AEs by age that occurred up to 30 days after the last dose of study medication.

Treatment emergent AEs by hepatis B and hepatitis C serology status that occurred up to 30 days post last dose.

Defined as HIV-1 RNA levels < 400 Copies/mL or at least 0.5 Log 10-decrease from baseline in HIV-1 RNA levels.

Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference.

Defined as HIV-1 RNA levels < 400 copies/mL or at least 1.0 Log 10-decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference.

Limit of quantification defined as <400 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference.

Limit of quantification defined as <50 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference.

Change from baseline in cluster of differentiation 4 helper T cells (CD4) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value.

Change from baseline in CD4 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value.

Change from baseline in cluster of differentiation 8 suppressor T cells (CD8) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value.

Change from baseline in CD8 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value.

Computed as time from the first dose of study medication to the loss of virologic response. Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥ 0.5 log10 copies /mL by the second viral load determination (unless viral load was below the lower limit level of quantification [LLOQ]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving a HIV 1 RNA reduction from BL >0.5 log10 copies/mL; or a HIV 1 RNA level of >1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ.

Reasons for virologic failure: A) failure to achieve a reduction in HIV-1 RNA>=0.5 log10 copies/ml from baseline (BL) by second viral load determination (unless below level of quantification [LOQ]); B) >=0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from BL >0.5 log10 copies/ml ; C) HIV-1 RNA >1000 copies/ml after having achieved an HIV-1 RNA below LOQ.

Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable [NR]) at Screening (Scr) and time of virologic failure (V fail). Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥0.5 log10 copies/mL by second viral load determination (unless viral load was below lower limit level of quantification [LLOQ]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving HIV 1 RNA reduction from BL >0.5 log10 copies/mL; or a HIV 1 RNA level of >1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ.

Resistance to maravroc in viruses from participants failing therapy with R5 virus was investigated using the in vitro phenotypic (drug susceptibility) assay. The number of participants who failed with R5 virus were assessed successfully for maraviroc susceptibility at Baseline and Last on--treatment (Week 144). Samples were analyzed for change from Baseline to time of virologic failure in IC 50 and presence of plateau. A maximal percent inhibition (MPI) <95% established as a plateau in inhibition at high concentrations of maraviroc was used to identify viruses which had reduced phenotypic susceptibility to maraviroc.

Virus from participants who experienced virologic failure was analyzed for resistance to maraviroc. Resistance testing was performed on archived samples of participants which were available pre--treatment at time of virologic failure. For participants who met definition of virologic failure during the trial, the sequencing of the V3 loop of HIV--1 viral envelope gp 120 was evaluated to identify any amino acid changes concomitant with decreased susceptibility to maraviroc.