This multicenter phase I study aimed to establish the recommended dose (RD) of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, given as monotherapy or with radiotherapy to children with malignant brain tumors. Group 1 included patients with refractory or relapsing brain tumors receiving erlotinib alone, and group 2 included newly diagnosed patients with brainstem gliomas receiving radiotherapy and erlotinib. A conventional 3 + 3 dose escalation and a continual reassessment method, respectively, were utilized in 4 dose levels: 75, 100, 125, and 150 mg/m² per day. Fifty-one children were enrolled (30 and 21, respectively); 50 received treatment. The RD of erlotinib was 125 mg/m² per day as monotherapy or in combination with radiotherapy. Overall, 230 adverse events in 44 patients were possibly treatment related (216, grades 1 and 2; 9, grade 3; 1, grade 4; 4, grade 5). Dermatologic and neurologic symptoms were common; intratumoral hemorrhage was confirmed in 3 patients. In group 1, 8 of 29 patients (28%) had stable disease with tumor regression approaching 50% in a malignant glioma and an anaplastic oligoastrocytoma. In group 2, overall survival was 12.0 months. EGFR overexpression by immunohistochemistry was found in 17 of 38 (45%) tumor samples analyzed, with a partial gain of 7p11.2 in 1 glioblastoma; phosphate and tensin homolog loss was frequent in brainstem glioma (15 of 19). Mean (95% CI) apparent clearance and volume of distribution for erlotinib were 4.0 L/h (3.4-4.5 L/h) and 98.6 L (69.8-127.0 L), respectively, and were independent of the dose level; mean half-life was 16.6 hours. Thus, erlotinib 125 mg/m² per day has an acceptable tolerability profile in pediatric patients with brain tumors and can be combined with radiotherapy.

The Senegal pre-exposure prophylaxis (PrEP) Demonstration Project was an open-label cohort study assessing the delivery of daily oral PrEP to HIV-negative female sex workers (FSWs) in four Ministry of Health (MoH)-run clinics in Dakar, Senegal. We assessed uptake, retention in care, and adherence over up to 12 months of follow-up as well as HIV infection rates. Between July and November 2015, 350 individuals were approached and 324 (92.6%) were preliminarily eligible. Uptake was high, with 82.4% of eligible participants choosing to enroll and take PrEP. The mean age of those enrolled was 37.7 years (SD = 8.7), and approximately half had not attended school (41.2%). Among the 267 participants who were prescribed PrEP, 79.9 and 73.4% were retained in PrEP care at 6 and 12 months, respectively. Older age among FSWs was found to be the only significant predictor of lower discontinuation. We did not find significant differences in retention by site, education, condom use, or HIV risk perception. There were no new HIV infections at follow-up. Our results showed evidence of high interest in PrEP and very good PrEP retention rates among FSWs at 12-month follow-up when offered in MoH-run clinics, with older age as the only significant predictor of higher PrEP retention. This highlights the role that these clinics can play in expanding PrEP access nationwide.

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PurposeCancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA.MethodsWe established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array.ResultsWe used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories.ConclusionWe provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

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Background Preexposure prophylaxis (PrEP) can reduce HIV acquisition among female sex workers (FSWs). However, changes in condomless sex frequency after PrEP initiation could reduce PrEP effectiveness when PrEP adherence is suboptimal as well as increase the risk of acquiring other sexually transmitted infections. Objective measures of condomless sex may be more accurate for determining changes in sexual behavior than self-reported measures. Methods We longitudinally measured self-reported condom use, number of clients, and presence of Y-chromosomal DNA (Yc-DNA) in vaginal swabs among 267 FSWs accessing PrEP at 4 clinics in Senegal between 2015 and 2016. We assessed trends in sexual behavior over time since PrEP initiation using generalized estimating equations and evaluated predictors of Yc-DNA detection. Results We found no increase in self-reported condomless sex with clients (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89–1.00), main partners (OR, 0.99; 95% CI, 0.96–1.02), or Yc-DNA detection (OR, 0.99; 95% CI, 0.90–1.08) over time since initiation. Y-chromosomal DNA was detected in 34 (22%) of 154 swabs tested and in 15 (26%) of 58 swabs from FSW reporting consistent condom use among both clients and main partners. Self-reported condom use with clients or main partners did not predict Yc-DNA detection. Conclusions In a FSW PrEP demonstration project in Senegal, we found no evidence of risk compensation among FSWs on PrEP as measured by self-reported behavior or through Yc-DNA detection. Y-chromosomal DNA detection was frequently detected among FSWs reporting consistent condom use, highlighting limitations of self-reported sexual behavioral measures.