These guidelines were developed by CDC staff who worked with subject matter experts with expertise in STI clinical management from other federal agencies, nongovernmental academic and research institutions, and professional medical organizations. CDC staff identified governmental and nongovernmental subject matter experts on the basis of their expertise and assisted them in developing questions to guide individual literature reviews. CDC staff informed the subject matter experts that they were being consulted to exchange information and observations and to obtain their individual input. All subject matter experts disclosed potential conflicts of interest. STI Treatment Guidelines, 2021, Work Group members are listed at the end of this report.

In 2018, CDC staff identified key questions about treatment and clinical management to guide an update of the 2015 STD treatment guidelines (1). To answer these questions and synthesize new information available since publication of the 2015 guidelines, subject matter experts and CDC staff collaborated to conduct systematic literature reviews by using an extensive MEDLINE database evidence-based approach for each section of the 2015 guidelines (e.g., using English-language published abstracts and peer reviewed journal articles). These systematic reviews were focused on four principal outcomes of STI therapy for each disease or infection: 1) treatment of infection on the basis of microbiologic eradication; 2) alleviation of signs and symptoms; 3) prevention of sequelae; and 4) prevention of transmission, including advantages (e.g., cost-effectiveness, single-dose formulations, and directly observed therapy) and disadvantages (e.g., adverse effects) of specific regimens. The outcome of the literature reviews guided development of background materials, including tables of evidence from peer-reviewed publications summarizing the type of study (e.g., randomized controlled trial or case series), study population and setting, treatments or other interventions, outcome measures assessed, reported findings, and weaknesses and biases in study design and analysis.

In June 2019, the subject matter experts presented their assessments of the literature reviews at an in-person meeting of governmental and nongovernmental participants. Each key question was discussed and pertinent publications were reviewed in terms of strengths, weaknesses, and relevance. Participants evaluated the quality of evidence, provided their input, and discussed findings in the context of the modified rating system used by the U.S. Preventive Services Task Force (USPSTF). The discussions were informal and not structured to reach consensus. CDC staff also reviewed the publications from other professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), USPSTF, the American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP), and the Advisory Committee on Immunization Practices (ACIP). The discussion culminated in a list of participants’ opinions on all the key STI topic areas for consideration by CDC. (More detailed descriptions of the key questions, search terms, systematic search, evidence tables, and review process are available at

CDC staff then independently reviewed the tables of evidence prepared by the subject matter experts, individual comments from the participants and professional organizations, and existing guidelines from other organizations to determine whether revisions to the 2015 STD treatment guidelines were warranted. CDC staff ranked evidence as high, medium, and low on the basis of each study’s strengths and weaknesses according to the USPSTF ratings ( icon). CDC staff then developed draft recommendations that were peer reviewed by public health and clinical experts as defined by the Office of Management and Budget for influential scientific information. A public webinar was held to provide an overview of the draft recommendations and invite questions and comments on the draft recommendations. The peer review comments, webinar, questions, and responses were considered by CDC staff in developing the final recommendations for the updated STI treatment guidelines. Recommendations for HIV, hepatitis C, cervical cancer screening, STI screening in pregnancy, human papillomavirus (HPV) testing, and hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination were developed after CDC staff reviewed existing published recommendations. The English-language literature was searched periodically by CDC staff to identify subsequently published articles warranting consideration.

Throughout this report, the evidence used as the basis for specific recommendations is discussed briefly. Publication of comprehensive, annotated discussions of such evidence is planned in a supplemental issue of the journal Clinical Infectious Diseases after publication of the treatment guidelines. When more than one therapeutic regimen is recommended and the listed regimens have similar efficacy and similar rates of intolerance or toxicity, the recommendations are listed alphabetically. If differences are specified, regimens are prioritized on the basis of these differences. Recommended regimens should be used primarily; alternative regimens can be considered in instances of notable drug allergy or other medical contraindications to the recommended regimens. Alternative regimens are considered inferior to recommended regimens on the basis of available evidence regarding the principal outcomes and disadvantages of the regimens.