Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study.

BACKGROUND: Patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma for whom treatment has failed with both Bruton tyrosine kinase (BTK) inhibitor and venetoclax have few treatment options and poor outcomes. We aimed to evaluate the efficacy and safety of lisocabtagene maraleucel (liso-cel) at the recommended phase 2 dose in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma. METHODS: We report the primary analysis of TRANSCEND CLL 004, an open-label, single-arm, phase 1-2 study conducted in the USA. Patients aged 18 years or older with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma and at least two previous lines of therapy, including a BTK inhibitor, received an intravenous infusion of liso-cel at one of two target dose levels: 50 × 106 (dose level 1) or 100 × 106 (dose level 2, DL2) chimeric antigen receptor-positive T cells. The primary endpoint was complete response or remission (including with incomplete marrow recovery), assessed by independent review according to the 2018 International Workshop on Chronic Lymphocytic Leukemia criteria, in efficacy-evaluable patients with previous BTK inhibitor progression and venetoclax failure (the primary efficacy analysis set) at DL2 (null hypothesis of ≤5%). This trial is registered with ClinicalTrials.gov, NCT03331198. FINDINGS: Between Jan 2, 2018, and June 16, 2022, 137 enrolled patients underwent leukapheresis at 27 sites in the USA. 117 patients received liso-cel (median age 65 years [IQR 59-70]; 37 [32%] female and 80 [68%] male; 99 [85%] White, five [4%] Black or African American, two [2%] other races, and 11 [9%] unknown race; median of five previous lines of therapy [IQR 3-7]); all 117 participants had received and had treatment failure on a previous BTK inhibitor. A subset of patients had also experienced venetoclax failure (n=70). In the primary efficacy analysis set at DL2 (n=49), the rate of complete response or remission (including with incomplete marrow recovery) was statistically significant at 18% (n=9; 95% CI 9-32; p=0·0006). In patients treated with liso-cel, grade 3 cytokine release syndrome was reported in ten (9%) of 117 (with no grade 4 or 5 events) and grade 3 neurological events were reported in 21 (18%; one [1%] grade 4, no grade 5 events). Among 51 deaths on the study, 43 occurred after liso-cel infusion, of which five were due to treatment-emergent adverse events (within 90 days of liso-cel infusion). One death was related to liso-cel (macrophage activation syndrome-haemophagocytic lymphohistiocytosis). INTERPRETATION: A single infusion of liso-cel was shown to induce complete response or remission (including with incomplete marrow recovery) in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma, including patients who had experienced disease progression on a previous BTK inhibitor and venetoclax failure. The safety profile was manageable. FUNDING: Juno Therapeutics, a Bristol-Myers Squibb Company.

Clinical validation of three-dimensional ultrasound for abdominal aortic aneurysm.

OBJECTIVE: Three-dimensional ultrasound (3D-US) examination is a relatively new modality that can be used for abdominal aortic aneurysm (AAA) surveillance, and may offer improved reproducibility over conventional two-dimensional ultrasound (2D-US) examination. The aim of this study was to evaluate the interoperator reproducibility of maximum anterior-to-posterior diameter by nonphysician ultrasound technicians in a typical vascular laboratory setting, on patients with infrarenal AAAs using 3D-US and 2D-US examination. METHODS: A total of 134 consecutive patients with asymptomatic infrarenal AAAs were screened. Of the 134 patients, 28 (21%) were screen failures. From the remaining 106 patients, 3 (2.8%) had missing data and 13 (12.3%) had technically unacceptable image quality. As a result, 90 patients were included for final analysis. Ultrasound image acquisitions were performed during the single visit. The 2D-US images were evaluated at the time of examination by the respective ultrasound technicians who acquired them. All 3D-US images were evaluated offline by both ultrasound technicians after a wash-out period of at least 6 weeks. RESULTS: Excellent interoperator reproducibility was observed for measuring maximum diameter using 3D-US (intraclass correlation coefficient, 0.97), and good agreement among ultrasound technicians (mean difference, -0.08 mm; limits of agreement, -3.17; 3.00 mm). When using 3D-US examination, 74 of the 90 patients (82%) were estimated within 2 mm of interoperator variability. Of 90 patients, 52 (58%) were estimated to be within the same variability by 2D-US examination. Estimating AAA diameter using 3D-US was superior to 2D-US with respect to interoperator reproducibility. CONCLUSIONS: Both 3D-US and 2D-US examination demonstrated good reproducibility among two vascular ultrasound technicians with superior agreement from 3D-US examination. The present results support the broader use of 3D-US in standard AAA surveillance programs.

A Comparison of the Effect of Two Power Toothbrushes on the Reduction of Gingival Inflammation and Supragingival Plaque.

OBJECTIVES: To compare the effect of the Philips Sonicare DiamondClean Smart and Oral-B Genius 8000 powered toothbrushes on gingivitis, gingival bleeding, and supragingival plaque reduction following 42 days of home use. METHODS: This was a randomized, parallel, examiner-blinded, prospective clinical trial with two treatment groups. Eligible participants were generally healthy volunteers who were manual toothbrush users, non-flossers, 18-65 years of age. The subject panel included non-smokers with = 50 sites of gingival bleeding according to the Gingival Bleeding Index (GBI), and a supragingival plaque score of = 1.8 per Modified Plaque Index (MPI) at 3-6 hours following last tooth brushing encounter. Eligible subjects were randomized to use either a Philips Sonicare DiamondClean Smart with Premium Plaque Control brush head (DCS) or an Oral-B Genius 8000 with FlossAction brush head (OBG) for home use. Each toothbrush was used twice daily for two minutes. All subjects used a standardized fluoride-containing dentifrice. All other oral hygiene measures were prohibited. Subjects returned at Day 14 for an interim compliance and safety assessment, and at Day 42 for the final safety and efficacy assessments. RESULTS: Of 222 enrolled and eligible subjects, 219 completed (112 in the SDC group, 107 in the OBG group) the study. The least squares (LS) mean and 95% confidence interval (CI) estimates for gingivitis reduction and percent reduction per Modified Gingival Index (MGI) following 42 days of product home use were 1.38 (1.30, 1.46) and 51.32% (48.45%, 54.19%) for DCS, and 0.53 (0.45, 0.61) and 20.07% (17.14%, 23.00%) for OBG. The differences, expressed as either reduction or percent reduction, were statistically significant between the two groups, p < 0.001. Statistically significant differences were also observed between products at Day 42 for the gingival bleeding and supragingival plaque reduction endpoints, p < 0.001. There were two reported adverse events. CONCLUSIONS: The Philips Sonicare DiamondClean Smart powered toothbrush reduced gingival inflammation, gingival bleeding, and supragingival plaque significantly more than the Oral-B Genius 8000 powered toothbrush following a 42-day home-use period. Both products were safe for use.

The Effects of Use of a Powered and a Manual Home Oral Hygiene Regimen on Plaque and Gum Health in an Orthodontic Population.

OBJECTIVES: The objective of this study was to compare the effect of two home use oral hygiene regimens on plaque, gingivitis, and gingival bleeding on subjects undergoing orthodontic treatment with fixed appliances. METHODS: This was a randomized, parallel, single-center clinical trial. Eligible study subjects fit the following profile: age 12-65 years; nonsmoker; plaque score of = 2.0 per Bonded Bracket Index (BBI) on dentition with fixed orthodontic hardware; minimum of 10 orthodontic brackets in each arch or on all teeth from first molar to first molar; presenting with mild to moderate gingivitis, defined as a score of = 1 on at least 20 sites per Gingival Bleeding Index (GBI). Subjects with advanced periodontal disease or gingival recession were not eligible. Eligible subjects were randomized to one of two home use oral hygiene regimens: manual toothbrush plus string floss (used with a threading device) for interdental cleaning (MTF regimen); or Philips Sonicare EasyClean power toothbrush with InterCare brush head and AirFloss Pro powered device, used with BreathRx mouthrinse for interdental cleaning (Sonicare Orthodontic Regimen or SOR). All subjects brushed twice daily with standard fluoridated dentifrice and performed interdental cleaning once daily. Efficacy and safety examinations were performed at Baseline and following three and six weeks of home use of the study products, and included assessments of BBI, GBI, Modified Gingival Index (MGI), and Modified Plaque Index (MPI). RESULTS: Of 228 enrolled subjects, 223 were included in the primary analysis. For the primary endpoint, reduction in BBI score following three weeks of product use, the overall least squares (LS) mean (95% CI) reduction was 0.89 (0.84, 0.95) for SOR and 0.06 (0.01, 0.12) for MTF. Expressed as percent reduction (95% CI) from Baseline, this was 33.1% (31.1%, 35.2%) for SOR and 2.01% (-0.06%, 4.07%) for MTF. The differences between regimens were statistically significant, p < 0.0001. Statistically significant differences between regimens were observed in BBI following six weeks of product use, and also for all other efficacy variables (GBI, MGI, MPI) at Week 3 and Week 6. CONCLUSIONS: The powered oral hygiene regimen was significantly more effective than a manual regimen in reducing plaque on bracketed and non-bracketed teeth, and in reducing gingival bleeding and gingival inflammation in orthodontic subjects following three weeks of use and persisting following six weeks of use. All products were safe on oral tissues and fixed orthodontic appliances.

A Randomized Parallel Study to Compare the Effects of Powered and Manual Tooth Brushing on Gingival Health and Plaque.

OBJECTIVES: To compare the effect of powered and manual tooth brushing on plaque and gingivitis following two and six weeks of home use. METHODS: This was a randomized, three-arm, parallel-design clinical trial. Eligible participants were manual toothbrush users who were generally healthy non-smokers, aged 18-65 years, with a plaque score of = 1.8 per Lobene and Soparkar Modified Plaque Index (MPI), and mild to moderate gingivitis, defined as a Gingival Bleeding Index (GBI) = 1 on at least 20 sites. Subjects with advanced periodontal disease, excessive gingival recession, and heavy deposits of calculus or rampant decay were excluded. Enrolled participants were randomly dispensed one of three devices: a powered toothbrush (Philips Sonicare DiamondClean Smart with Premium Gum Care brush head) used in either Gum Heath mode (DC-GH) or Clean mode (DC-C), or an ADA reference manual toothbrush (MTB). Efficacy and safety variables were assessed at Baseline, and at two and six weeks following twice-daily product home use. RESULTS: For the primary endpoint, reduction in gingivitis per Modified Gingival Index (MGI) at Week 2, 188 subjects completed and were included in the analysis. Expressed as percent reduction from Baseline, the adjusted mean reduction and Standard Error (SE) estimates were 60.31% (1.95%) for DC-GH, 53.08% (1.95%) for DC-C, and 16.59% (1.96%) for MTB. The difference between each power toothbrush group and the manual toothbrush was statistically significant (p < 0.0001). Statistically significant differences were also observed between DC-GH, DC-C, and manual tooth brushing for MGI at Week 6, as well as for MPI and GBI at Weeks 2 and 6. CONCLUSIONS: The powered toothbrush, used in either Gum Health or Clean mode, was statistically significantly superior to a manual tooth brush in reducing gingival inflammation, gingival bleeding, and plaque following two and six weeks of home use.

Assessment of contamination and misclassification biases in a randomized controlled trial of a social network peer education intervention to reduce HIV risk behaviors among drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand.

Controlled trials of HIV prevention and care interventions are susceptible to contamination. In a randomized controlled trial of a social network peer education intervention among people who inject drugs and their risk partners in Philadelphia, PA and Chiang Mai, Thailand, we tested a contamination measure based on recall of intervention terms. We assessed the recall of test, negative and positive control terms among intervention and control arm participants and compared the relative odds of recall of test versus negative control terms between study arms. The contamination measures showed good discriminant ability among participants in Chiang Mai. In Philadelphia there was no evidence of contamination and little evidence of diffusion. In Chiang Mai there was strong evidence of diffusion and contamination. Network structure and peer education in Chiang Mai likely led to contamination. Recall of intervention materials can be a useful method to detect contamination in experimental interventions.

HPTN 062: a feasibility and acceptability pilot intervention to reduce HIV transmission risk behaviors among individuals with acute and early HIV infection in Lilongwe, Malawi.

Acute HIV infection (AHI) is a relatively brief period of time when individuals are highly infectious and the opportunity to intervene to prevent forward transmission is extremely limited. HPTN 062 partnered with CHAVI 001 to evaluate the feasibility and acceptability of a motivational interviewing (MI)-based counseling intervention to reduce HIV-transmission risk behaviors among individuals with acute and early HIV infection in Lilongwe, Malawi. Participants were randomized to receive either (1) brief education sessions about HIV and AHI; or (2) the same brief education sessions plus an MI-based counseling intervention called Uphungu Wanga. Although Uphungu Wanga was determined to be feasible and acceptable, few major differences existed between the two arms with regard to acceptability, feasibility, and self-reported sexual behaviors. We therefore conclude that an additional MI-based counseling intervention may not be needed during the short period of AHI. Instead, we recommend that individuals with AHI receive frequent, but brief, counseling immediately after diagnosis and then transition to receiving counseling at less frequent intervals until they can initiate antiretroviral therapy. Other recommendations are provided.

Undisclosed antiretroviral drug use in a multinational clinical trial (HIV Prevention Trials Network 052).

The HIV Prevention Trials Network 052 study enrolled serodiscordant couples. Index participants infected with human immunodeficiency virus reported no prior antiretroviral (ARV) treatment at enrollment. ARV drug testing was performed retrospectively using enrollment samples from a subset of index participants. ARV drugs were detected in 45 of 96 participants (46.9%) with an undetectable viral load, 2 of 48 (4.2%) with a low viral load, and 1 of 65 (1.5%) with a high viral load (P < .0001); they were also detected in follow-up samples from participants who were not receiving study-administered treatment. ARV drug testing may be useful in addition to self-report of ARV drug use in some clinical trial settings.

Differences in substance use, psychosocial characteristics and HIV-related sexual risk behavior between Black men who have sex with men only (BMSMO) and Black men who have sex with men and women (BMSMW) in six US cities.

We assessed associations in substance use, psychosocial characteristics, and HIV-related sexual risk behaviors, comparing characteristics of Black men who only have sex with other men only (BMSMO; n = 839) to Black men who have sex with men and women (BMSMW; n = 590). The study analyzed baseline data from the HIV Prevention Trials Network Brothers Study (HPTN 061), a feasibility study of a multi-component intervention for Black MSM in six US cities. Bivariate analyses compared BMSMO to BMSMW along demographics, substance use, psychosocial characteristics, and HIV-related sexual risk behaviors. Logistic regression models then assessed multivariable associations between being BMSMW and the odds of engaging in HIV-related sexual risk behaviors. Adjusted analyses revealed that BMSMW remained more likely to have unprotected anal intercourse while under the influence of alcohol (AOR: 1.45; 95 % CI:1.11-1.90) and were more likely to receive money/drugs for sex (AOR: 2.11; 95 % CI:1.48-3.03), compared to BMSMO. Substance use is an important factor to be considered when developing risk-reduction interventions for BMSMW. Structural interventions that address factors that may contribute to exchange sex among these men are also warranted.

Comparison of a high-resolution melting assay to next-generation sequencing for analysis of HIV diversity.

Next-generation sequencing (NGS) has recently been used for analysis of HIV diversity, but this method is labor-intensive, costly, and requires complex protocols for data analysis. We compared diversity measures obtained using NGS data to those obtained using a diversity assay based on high-resolution melting (HRM) of DNA duplexes. The HRM diversity assay provides a single numeric score that reflects the level of diversity in the region analyzed. HIV gag and env from individuals in Rakai, Uganda, were analyzed in a previous study using NGS (n = 220 samples from 110 individuals). Three sequence-based diversity measures were calculated from the NGS sequence data (percent diversity, percent complexity, and Shannon entropy). The amplicon pools used for NGS were analyzed with the HRM diversity assay. HRM scores were significantly associated with sequence-based measures of HIV diversity for both gag and env (P < 0.001 for all measures). The level of diversity measured by the HRM diversity assay and NGS increased over time in both regions analyzed (P < 0.001 for all measures except for percent complexity in gag), and similar amounts of diversification were observed with both methods (P < 0.001 for all measures except for percent complexity in gag). Diversity measures obtained using the HRM diversity assay were significantly associated with those from NGS, and similar increases in diversity over time were detected by both methods. The HRM diversity assay is faster and less expensive than NGS, facilitating rapid analysis of large studies of HIV diversity and evolution.

A phase II study of estramustine, docetaxel, and exisulind in patients with hormone- refractory prostate cancer: results of cancer and leukemia group B trial 90004.

PURPOSE: Docetaxel/estramustine is a known active regimen in hormonerefractory prostate cancer (HRPC). A phase II study was conducted to assess the safety and efficacy of docetaxel/estramustine combined with exisulind, an apoptotic antineoplastic drug. PATIENTS AND METHODS: Eighty men with chemotherapy-naive HRPC were enrolled in a multicenter, cooperative group study. The treatment regimen consisted of oral estramustine (280 mg 3 times daily for 5 days), docetaxel 70 mg/m2, oral exisulind (250 mg twice daily), oral dexamethasone (8 mg twice daily for 3 days), and oral warfarin (2 mg daily). RESULTS: Seventy-five eligible patients were treated with a median of 6 cycles of therapy. Fortyseven patients (62.7%; 95% CI, 50.7%-73.6%) had a > or = 50% decline in prostate-specific antigen levels. Forty-six patients had measurable disease with 6 partial responses (13%; 95% CI, 4.9%-26.3%). The main grade 3/4 toxicities were neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time to first progression was 5.1 months (95% CI, 4.4-6.3 months) and the median survival time was 17.8 months (95% CI, 14.7-20.1 months). CONCLUSION: The combination of estramustine/docetaxel/exisulind was associated with significant thomboembolic toxicity despite prophylactic warfarin. The contribution of exisulind to toxicity is uncertain. Prostate-specific antigen decline, response rates, and progression-free and overall survival are similar to those reported with docetaxel/estramustine.

Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer and leukemia group B study.

PURPOSE: Adrenal androgens activate the androgen receptor and stimulate prostate cancer growth. Ketoconazole is used as an inhibitor of adrenal androgen synthesis in men with androgen-independent prostate cancer. This study analyzes the relationship between pretreatment androgen levels and outcome following ketoconazole treatment. EXPERIMENTAL DESIGN: Baseline levels of three adrenal androgens (androstenedione, dehydroepiandrostenedione, and dehydroepiandrostenedione-sulfate) and testosterone were measured. Regression models (logistic and proportional hazard) were used to assess the prognostic significance of these levels in predicting overall survival and prostate-specific antigen (PSA) response defined by Consensus Criteria. RESULTS: In 103 patients with available levels, PSA response rate was 28% and median response duration was 4.8 months. The median baseline androstenedione level was 0.64 ng/mL and was 0.88 ng/mL versus 0.53 ng/mL for those with and without a PSA response, respectively (P = 0.034). In univariate analysis, elevation of baseline androstenedione levels was predictive of PSA response [odds ratio, 2.26; 95% confidence interval (95% CI), 1.03-4.96; P = 0.043]. In multivariate analysis, both the uppermost and the middle tertile of baseline androstenedione level were associated with an improved overall survival compared with those in the lower tertile (hazard ratio, 0.59; 95% CI, 0.36-0.98; P = 0.40; hazard ratio, 0.53; 95% CI, 0.32-0.90; P = 0.018, respectively). A linear correlation was observed among all androgen levels. CONCLUSIONS: Higher androstenedione levels predict likelihood of response to ketoconazole and improved survival compared with patients with lower levels. These data suggest that therapy with ketoconazole is less effective in patients with low levels of androgen at baseline.

Differential Patterns of Risk and Vulnerability Suggest the Need for Novel Prevention Strategies for Black Bisexual Men in the HPTN 061 Study.

BACKGROUND: Black men who have sex with men (BMSM) and some who also have sex with women (BMSMW) account for over 70% of new HIV infections in the United States representing an elevated HIV risk in this group, also informing risks of HIV transmission to other BMSM and female sexual partners. SETTINGS: We examined trajectories of self-reported substance use, HIV-related sexual risk behaviors, and psychosocial vulnerabilities among BMSMW versus BMSM over a 1-year study period. METHODS: We analyzed baseline, 6-, and 12-month follow-up data from the HIV Prevention Trials Network "BROTHERS" Study (HPTN 061; n = 1126). Categorizing participants by sexual partner type across 3 time points: (1) BMSMO: having male and no female partners across assessments and (2) BMSMW: having sex with male and one or more female partners at least at 1 time point. Using generalized estimating equations, we estimated associations between being BMSMW (versus BMSMO) and changes in psychosocial vulnerability, substance use, and HIV-related sexual risk behaviors. RESULTS: Generalized estimating equation models controlling for sociodemographics, time-varying effects, and intervention status showed that BMSMW versus BMSMO had 50% increased odds of crack use, 71% increased odds of alcohol use during condomless anal intercourse (CAI), 51% greater odds of using drugs at last CAI, and twice the odds of receiving goods at last CAI. CONCLUSIONS: Findings show stable and comparatively elevated illicit drugs, alcohol, and exchange sex during last CAI among BMSMW. Future intervention research should focus on ways to address changes in substance-related HIV-transmission behaviors over time in this population of men.

Comparison of Hepatitis B Virus Infection in HIV-Infected and HIV-Uninfected Participants Enrolled in a Multinational Clinical Trial: HPTN 052.

OBJECTIVE: Data comparing hepatitis B virus (HBV) infection in HIV-infected [HIV(+)], and HIV-uninfected [HIV(-)] individuals recruited into the same study are limited. HBV infection status and chronic hepatitis B (cHB) were characterized in a multinational clinical trial: HIV Prevention Trials Network (HPTN 052). METHOD: HBV infection status at enrollment was compared between HIV(+) (N = 1241) and HIV(-) (N = 1232) from 7 HBV-endemic countries. Hepatitis B e antigen and plasma HBV DNA were determined in cHB. Median CD4, median plasma HIV RNA, and prevalence of transaminase elevation were compared in HIV(+) with and without cHB. Significance was assessed with χ, Fisher exact, and median tests. RESULTS: Among all participants, 33.6% had HBV exposure without cHB (8.9% isolated HBV core antibody, "HBcAb"; 24.7% HBcAb and anti-HB surface antibody positive, "recovered"), 4.3% had cHB, 8.9% were vaccinated, and 53.5% were uninfected. Data were similar among HIV(+) and HIV(-) except for isolated HBcAb, which was more prevalent in HIV(+) than HIV(-) [10.1% vs. 7.7%, P = 0.046]. Median HBV DNA trended higher in HIV(+) than in HIV(-). In HIV(+) with cHB versus those without cHB, transaminase elevations were more prevalent (alanine aminotransferase ≤ grade 2, 12% vs. 5.2%, P = 0.037; aspartate aminotransferase ≤ grade 2, 26% vs. 6.0%, P < 0.001), CD4 trended lower, and HIV RNA was similar. CONCLUSIONS: HBV infection status did not differ by HIV infection status. HIV co-infection was associated with isolated HBcAb and a trend of increased HBV DNA. In HIV, cHB was associated with mild transaminase elevations and a trend toward lower CD4.

Virologic outcomes in early antiretroviral treatment: HPTN 052.

INTRODUCTION: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. OBJECTIVE: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. METHODS: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. RESULTS: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. CONCLUSIONS: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

Treatment as Prevention: Characterization of Partner Infections in the HIV Prevention Trials Network 052 Trial.

HIV Prevention Trials Network 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner's infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: 4 near the time of ART initiation and 4 after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART.

Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study.

PURPOSE: Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients. MATERIAL AND METHODS: Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow biopsies were obtained from 184 patients who underwent an office-based, unguided bone marrow biopsy of the posterior iliac crest. RESULTS: Forty-seven of the 184 patients (25.5%) had a positive bone marrow biopsy. When considered in a multivariate logistic regression analysis, lower hemoglobin levels, higher alkaline phosphatase, and higher lactate dehydrogenase levels were associated with a higher likelihood of a positive BMBx. The median survival time was 11 months (95% confidence interval, 8.0-14) among patients with a positive BMBx compared with 23 months (95% confidence interval, 19-27) with a negative BMBx. The median time to progression and time to prostate-specific antigen progression-free survival were also significantly decreased among positive BMBx patients. No patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137 patients with a negative BMBx survived beyond 5 years. DISCUSSION: Using common laboratory values, a specific patient cohort can be defined from whom the yield of a nonguided BMBx would be high enough to justify this approach. For studies that require broader entry criteria, a more directed approach with image guidance is recommended.

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

HPTN 062: A Pilot Randomized Controlled Trial Exploring the Effect of a Motivational-Interviewing Intervention on Sexual Behavior among Individuals with Acute HIV Infection in Lilongwe, Malawi.

OBJECTIVE: We pilot tested a Motivational Interviewing (MI) -based counseling intervention for individuals with Acute HIV Infection (AHI) to reduce risky sexual behavior in Lilongwe, Malawi. METHODS: Twenty-eight individuals diagnosed with AHI were randomized to receive either brief education alone, or the brief education plus the MI-based intervention, called Uphungu Wanga. Participants in Uphungu Wanga received four sessions delivered on the day of diagnosis, three days later and at weeks 1 and 2 with a booster session at week 8; participants were followed for 24 weeks from diagnosis. An interviewer administered quantitative questionnaire was conducted at baseline and at weeks 2, 4, 8, 12, 16, 20 and 24. Semi-structured qualitative interviews (SSI) were conducted at weeks 2, 8, 12, and 24. RESULTS: The majority of participants in both arms reported rapid and sustained behavior change following diagnosis with AHI. Very few participants reported having sex without a condom after diagnosis. Participants reported a trend towards fewer sex partners and abstaining from sex during study follow-up. Participants in the MI-based arm provided concrete examples of risk reduction strategies in the SSIs while those in the brief education arm primarily described reducing risk behavior, suggesting that the MI-based group may have acquired more risk reduction skills. CONCLUSIONS: Individuals in both study arms reduced risky sexual behaviors after diagnosis with AHI. We found few major differences between study arms during the 6-month follow up period in self-reported sexual behaviors therefore a MI-based intervention may not be needed to trigger behavior change following AHI. However, comparing the MI-based intervention to repeated brief education sessions made it difficult to assess the potential benefit of an MI-based intervention in a setting where standard counseling often consists of one post-test session. Nevertheless, provision of counseling immediately following diagnosis with HIV to support behavior change should remain a priority. TRIAL REGISTRATION: ClinicalTrials.gov NCT01197027.

Adherence to Early Antiretroviral Therapy: Results From HPTN 052, a Phase III, Multinational Randomized Trial of ART to Prevent HIV-1 Sexual Transmission in Serodiscordant Couples.

BACKGROUND: Combination antiretroviral therapy (ART) for HIV-1-infected individuals prevents sexual transmission if viral load is suppressed. METHODS: Participants were HIV-1-infected partners randomized to early ART (CD4 350-550) in HPTN052 (n = 886, median follow-up = 2.1 years), a clinical trial of early ART to prevent sexual transmission of HIV-1 in serodiscordant couples at 13 sites in 9 countries. Adherence was assessed through pill count (dichotomized at <95%) and through self-report items. Predictors of adherence were mental health and general health perceptions, substance use, binge drinking, social support, sexual behaviors, and demographics. Viral suppression was defined as HIV plasma viral load <400 copies per milliliter. Adherence counseling and couples' counseling about safer sex were provided. Logistic and linear regression models using generalized estimating equation for repeated measurements were used. FINDINGS: Through pill count, 82% of participants were adherent at 1 month and 83.3% at 1 year. Mental health was the only psychosocial variable associated with adherence [pill count, odds ratios (OR) = 1.05, 95% confidence intervals (CIs): 1.00 to 1.11; self-report parameter estimate, OR = 0.02, 95% CI: 0.01 to 0.04], although regional differences emerged. Pill count (OR = 1.19, 95% CI: 1.10 to 1.30) and self-report (OR = 1.42, 95% CI: 1.14 to 1.77) adherence were associated with viral suppression. INTERPRETATION: Although adherence was high among individuals in stable relationships taking ART for prevention, mental health and adherence covaried. Assessing and intervening on mental health in the context of promoting adherence to ART as prevention should be explored. Adherence and couples' counseling, feedback about viral suppression, and/or altruism may also help explain the magnitude of adherence observed.