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Competing Interests: The authors declare no conflicts of interest.

During antiretroviral therapy (ART) that suppresses HIV replication to below the limit-of-quantification, virions produced during ART can be detected at low frequencies in the plasma, termed residual viremia (RV). We hypothesized that a reservoir of HIV-infected cells actively produce and release virions during ART that are potentially infectious, and that following ART-interruption, these virions can complete full-cycles of replication and contribute to rebound viremia. Therefore, we studied the dynamics of RV sequence variants in 3 participants who initiated ART after ~3 years of infection and were ART-suppressed for >6 years prior to self-initiated ART-interruptions. Longitudinal RV C2V5env sequences were compared to sequences from pre-ART plasma, supernatants of quantitative viral outgrowth assays (QVOA) of cells collected during ART, post-ART-interruption plasma, and ART-re-suppression plasma. Identical, "putatively clonal," RV sequences comprised 8-84% of sequences from each timepoint. The majority of RV sequences were genetically similar to those from plasma collected just prior to ART-initiation, but as the duration of ART-suppression increased, an increasing proportion of RV variants were similar to sequences from earlier in infection. Identical sequences were detected in RV over a median of 3 years (range: 0.3-8.2) of ART-suppression. RV sequences were identical to pre-ART plasma viruses (5%), infectious viruses induced in QVOA (4%) and rebound viruses (5%) (total n = 21/154 (14%) across the 3 participants). RV sequences identical to ART-interruption "rebound" sequences were detected 0.1-7.4 years prior to ART-interruption. RV variant prevalence and persistence were not associated with detection of the variant among rebound sequences. Shortly after ART-re-suppression, variants that had been replicating during ART-interruptions were detected as RV (n = 5). These studies show a dynamic, virion-producing HIV reservoir that contributes to rekindling infection upon ART-interruption. The persistence of identical RV variants over years suggests that a subpopulation of HIV-infected clones frequently or continuously produce virions that may resist immune clearance; this suggests that cure strategies should target this active as well as latent reservoirs., Competing Interests: The authors have declared that no competing interests exist.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) are evidence- and consensus-based clinical practice guidelines addressing malignancies that affect more than 97% of all patients with cancer in the United States. The NCCN Guidelines are used extensively in the United States and globally. Use of the guidelines outside the United States has driven the need to adapt the guidelines based on local, regional, or national resources. The NCCN Guidelines Panels created, vetted, and continually update the NCCN Guidelines based on published scientific data on cancer detection, diagnosis, and treatment efficacy. The guidelines are developed within the context of commonly available resources, methods of payment, societal and cultural expectations, and governmental regulations as they exist in the United States. Although many of the cancer management recommendations contained in the NCCN Guidelines apply broadly from a global perspective, not all do. Disparities in availability and access to health care exist among countries, within countries, and among different social groups in the same country, especially regarding resources for cancer prevention, early detection, and treatment. In addition, different drug approval and payment processes result in regional variation in availability of and access to cancer treatment, especially highly expensive agents and radiation therapy. Differences in cancer risk, predictive biomarker expression, and pharmacogenetics exist across ethnic and racial groups, and therefore across geographic locations. Cultural and societal expectations and requirements may also require modification of NCCN Guidelines for use outside the United States. This article describes the adaptation process, using the recent Latin American adaptation of the 2013 NCCN Guidelines for Colorectal Cancer as an example.

The NCCN developed clinical practice guidelines for oncology that set the standard of cancer care in the United States. Because of wide acceptance of, need for, and interest in standardized treatment practices across the world, NCCN launched initiatives to help international groups adapt these guidelines. This article describes the initiative in the Middle East and North Africa (MENA) region. A group of oncology experts and key opinion leaders were assembled into 7 specific committees to develop treatment guidelines for breast cancer, lung cancer, colon cancer, prostate cancer, hepatobiliary cancer, lymphoma, and palliative care. The committees reviewed the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to identify any modifications required for them to be more applicable to the MENA region based on available evidence and regional experience. These modifications were discussed with NCCN experts and summarized for each specific area. The development of these guidelines generated a strong interest in the region to develop more evidence-based practice and create further networking and collaboration.

Background: Studies of adherence to breast cancer guidelines have often focused on primary therapies, but concordance with other guideline recommendations has not been examined as extensively. This study assesses the knowledge and practice patterns of medical oncologists in the United States to inform education and quality improvement initiatives that can improve breast cancer care., Methods: A survey containing case vignettes and related questions was developed to examine oncologists' clinical decision-making in evaluating and treating women with early breast cancer. The instrument was distributed to a random sample of 742 oncologists in the United States and yielded 205 responses (27.6% response rate). Responses from 184 practicing medical oncologists were analyzed relative to the 2007 NCCN Clinical Practice Guidelines in Oncology: Breast Cancer., Results: Most oncologists made guideline-consistent choices in clarifying indeterminate human epidermal growth factor 2 (HER2) status (85%), initial treatment for early breast cancer (95%), and postsurgical management of locally advanced breast cancer (82%). Guideline-discordant choices were seen in the lack of clip placement before neoadjuvant chemotherapy (36%), unnecessary use of PET scanning for initial assessment (34%), inappropriate assessment of menopausal status (33%), inappropriate use of tumor markers (22%), and use of chest imaging (16%) during posttherapeutic surveillance., Conclusions: Oncologists often make guideline-consistent choices, but discordant clinical decisions may occur in important aspects of care for early breast cancer. Broadening the diffusion and adoption of guideline recommendations is an important mechanism for addressing these gaps and may substantially improve the quality of breast cancer care.

Background: Longitudinal patient-provider relationships are a cornerstone of primary care. For many prevention services, better continuity of provider has been associated with better adherence to recommended practice. Our objective was to examine the relationship between continuity of care and chlamydia screening in adolescent and young women, a preventive service where large performance gaps exist., Methods: The study population included 4117 sexually active women aged 14-25 years continuously enrolled at a large U.S. HMO. Administrative data from 2000 to 2002 were used to document chlamydia testing, provider continuity, and selected covariates. We used logistic regression to examine the relationship between provider continuity and chlamydia testing after controlling for potential confounders., Results: 57.2% of eligible young women received a chlamydia test over the 2-year period. After controlling for utilization and other confounders, we found women in the lowest continuity of care quartile had 41% greater odds of being tested than those in the highest quartile (OR 1.41, 95% CI 1.14-1.76)., Conclusions: For adolescents and young women, the likelihood of testing for chlamydia was reduced when care was concentrated with a usual provider. Potential implications for health service delivery are discussed.