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Hardy et al J Acquir Immune Defic Syndr  Volume 55, Number 5, December 15, 2010 FIGURE 3. Adverse events occurring in $5% of patients at end of blinded therapy. Includes all patients who received at least 1 dose of study medication. If the same patient in a given treatment had more than 1 occurrence in the same preferred term event category, only the most severe occurrence is taken. Event counts are adjusted to 100 years of patient exposure. Includes data up to 7 days after last dose of study drug. RTI, respiratory tract infection. respectively, had plasma HIV-1 RNA,50 copies per milliliter at 96 weeks. More specifically, 86.7% and 81.4% of maraviroc twice a day or every day recipients with ,50 copies per milliliter atweek 48 also had undetectable HIV-1 RNAatweek 96. Moreover, well over half of the 10% of patients with plasma HIV-1 RNAbetween 50 and 400 copies per milliliter at week 96 subsequently resuppressed to ,50 copies per milliliter beyond week 96. Few subjects originally assigned to maraviroc treatment- experienced virologic failure between weeks 48 and 96. Coreceptor tropism screening before enrollment for this study was done using the original Trofile assay. During the first 48 weeks of the study, the suboptimal sensitivity of this assay may have contributed to virologic failures associated with emergence of previously undetected CXCR4-using virus.11,12 In the 83 subjects who had dual or mixed tropism at screening (n = 4) or at baseline (n = 79), the rate of virologic suppression (HIV-1 RNA ,50 copies/mL) was 18% in the placebo group (3 of 17 patients), as compared with 30% in the group receiving maraviroc once daily (10 of 33 patients) and 27% in the group receiving maraviroc twice daily (9 of 33 patients). The test for an interaction between treatment and tropism at baseline was not significant (P = 0.54). Among 228 patients with an R5 tropism result at baseline who were deemed virologic failures, 76 of 133 patients who received maraviroc had a dual or mixed or X4 tropism result (57%) and 57 patients had an R5 tropism result (43%). By comparison, 6 of 95 patients who received placebo (6%) had virus binding to CXCR4 that was detectable at treatment failure.4 Results from detailed virologic analyses of isolates from FIGURE 4. Incidence of A, total malignancies at week 48 and at end of blinded therapy, and B, exposure-adjusted malignancies by type at end of blinded therapy. *Includes anal cancer stage 0; **T-cell, B-cell and diffuse large B-cell lymphoma; †Includes testicular and tongue neoplasms; §Includes bone, liver and peritoneum; ‡Includes squamous cell carcinoma of the skin. 562 | www.jaids.com study patients failing a maraviroc regimen through week 48 revealed the following: (1) 115 of 160 (72%) of patients receiving maraviroc with a wOBTSS (weighted OBT susceptibility score)_. 2 were TLOVR ,50 responders with HIV-1 RNA ,50 copies per milliliter at week 48; (2) excluding non-R5 failures and those without matched maraviroc susceptibility data, R5 virologic failure occurred in 62 of 331 (19%) patients, with maraviroc-resistant HIV-1 seen in 22 of 62 (35%) of these; (3) functional monotherapy or a single active nucleoside reverse transcriptase inhibitor (wOBTSS ,1) accounted for 16 of 22 (73%) maraviroc resistance associated failures, and no maraviroc-resistant virus was found in patients with a wOBTSS of .2 who failed maraviroc treatment with an R5 tropism result; and (4) 16 of 80 (20%) patients who received functional monotherapy or q 2010 Lippincott Williams & Wilkins http://www.jaids.com

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JAIDS_55(5)558#564_RCI1AL4155