The Respond pillar of the Ending the HIV Epidemic in the U.S. initiative, which consists of activities also known as cluster and outbreak detection and response, offers a framework to guide tailored implementation of proven HIV prevention strategies where transmission is occurring most rapidly. Cluster and outbreak response involves understanding the networks in which rapid transmission is occurring; linking people in the network to essential services; and identifying and addressing gaps in programs and services such as testing, HIV and other medical care, pre-exposure prophylaxis, and syringe services programs. This article reviews the experience gained through 30 HIV cluster and outbreak responses in North America during 2000-2020 to describe approaches for implementing these core response strategies. Numerous jurisdictions that have implemented these response strategies have demonstrated success in improving outcomes related to HIV care and viral suppression, testing, use of prevention services, and reductions in transmission or new diagnoses. Efforts to address important gaps in service delivery revealed by cluster and outbreak detection and response can strengthen prevention efforts broadly through multidisciplinary, multisector collaboration. In this way, the Respond pillar embodies the collaborative, data-guided approach that is critical to the overall success of the Ending the HIV Epidemic in the U.S. initiative.

BACKGROUND: Transmitted HIV drug resistance can threaten the efficacy of antiretroviral therapy (ART) and preexposure prophylaxis (PrEP). Drug resistance testing is recommended at entry to HIV care in the United States and provides valuable insight for clinical decision-making and population-level monitoring. METHODS: We assessed transmitted drug resistance-associated mutation (TDRM) prevalence and predicted susceptibility to common HIV drugs among U.S. persons with HIV diagnosed during 2014-2018 who had a drug resistance test performed ≤3 months after HIV diagnosis and reported to the National HIV Surveillance System and who resided in 28 jurisdictions where ≥20% of HIV diagnoses had an eligible sequence during this period. RESULTS: Of 50,747 persons in the analysis, 9,616 (18.9%) had ≥1 TDRM. TDRM prevalence was 0.8% for integrase strand transfer inhibitors (INSTI), 4.2% for protease inhibitors, 6.9% for nucleoside reverse transcriptase inhibitors, and 12.0% for non-nucleoside reverse transcriptase inhibitors. Most individual mutations had a prevalence <1.0% including M184V (0.9%) and K65R (0.1%); K103N was most prevalent (8.6%). TDRM prevalence did not increase or decrease significantly during 2014-2018 overall, for individual drug classes, or for key individual mutations except for M184V (12.9% increase per year, 95% CI=5.6-20.6). CONCLUSIONS: TDRM prevalence overall and for individual drug classes remained stable during 2014-2018; transmitted INSTI resistance was uncommon. Continued population-level monitoring of INSTI and NRTI mutations, especially M184V and K65R, is warranted amidst expanding use of second-generation INSTI and PrEP.

Molecular cluster detection analyzes HIV sequences to identify rapid HIV transmission and inform public health responses. We describe changes in the capability to detect molecular clusters and in geographic variation in transmission dynamics. We examined the reporting completeness of HIV-1 polymerase sequences in quarterly National HIV Surveillance System datasets from December 2015 to December 2019. Priority clusters were identified quarterly. To understand populations recently affected by rapid transmission, we described the transmission risk and race/ethnicity of people in clusters first detected in 2018-2019. During December 2015 to December 2019, national sequence completeness increased from 26% to 45%. Of the 1212 people in the 136 clusters first detected in 2018-2019, 69% were men who have sex with men (MSM) and 11% were people who inject drugs (PWID). State-by-state analysis showed substantial variation in transmission risk and racial/ethnic groups in clusters of rapid transmission. HIV sequence reporting has increased nationwide. Molecular cluster analysis identifies rapid transmission in varied populations and identifies emerging patterns of rapid transmission in specific population groups, such as PWID, who, in 2015-2016, comprised only 1% of people in such molecular clusters. These data can guide efforts to focus, tailor, and scale up prevention and care services for these populations.

In 2014, persons aged 13-29 years represented 23% of the U.S. population, yet accounted for 40% of diagnoses of human immunodeficiency virus (HIV) infection during the same year (1). During 2010-2014, the rates of diagnosis of HIV infection decreased among persons aged 15-19 years, were stable among persons aged 20-24 years, and increased among persons aged 25-29 years (1). However, these 5-year age groups encompass multiple developmental stages and potentially mask trends associated with the rapid psychosocial changes during adolescence through young adulthood. To better understand HIV infection among adolescents aged 13-17 years and young adults aged 18-29 years in the United States and identify ideal ages to target primary HIV prevention efforts, CDC analyzed data from the National HIV Surveillance System (NHSS)* using narrow age groups. During 2010-2014, rates of diagnosis of HIV infection per 100,000 population varied substantially among persons aged 13-15 years (0.7), 16-17 years (4.5), 18-19 years (16.5), and 20-21 years (28.6), and were higher, but less variable, among persons aged 22-23 years (34.0), 24-25 years (33.8), 26-27 years (31.3), and 28-29 years (28.7). In light of the remarkable increase in rates between ages 16-17, 18-19, and 20-21 years, and a recent study revealing that infection precedes diagnosis for young persons by an average of 2.7 years (2), these findings demonstrate the importance of targeting primary prevention efforts to persons aged <18 years and continuing through the period of elevated risk in their mid-twenties.

PURPOSE: To assess the optimal age at which a one-time HIV screen should begin for adolescents and young adults (AYA) in the U.S. without identified HIV risk factors, incorporating clinical impact, costs, and cost-effectiveness. METHODS: We simulated HIV-uninfected 12-year-olds in the U.S. without identified risk factors who faced age-specific risks of HIV infection (.6-71.3/100,000PY). We modeled a one-time screen ($36) at age 15, 18, 21, 25, or 30, each in addition to current U.S. screening practices (30% screened by age 24). Outcomes included retention in care, virologic suppression, life expectancy, lifetime costs, and incremental cost-effectiveness ratios in $/year-of-life saved (YLS) from the health-care system perspective. In sensitivity analyses, we varied HIV incidence, screening and linkage rates, and costs. RESULTS: All one-time screens detected a small proportion of lifetime infections (.1%-10.3%). Compared with current U.S. screening practices, a screen at age 25 led to the most favorable care continuum outcomes at age 25: proportion diagnosed (77% vs. 51%), linked to care (71% vs. 51%), retained in care (68% vs. 44%), and virologically suppressed (49% vs. 32%). Compared with the next most effective screen, a screen at age 25 provided the greatest clinical benefit, and was cost-effective ($96,000/YLS) by U.S. standards (<$100,000/YLS). CONCLUSIONS: For U.S. AYA without identified risk factors, a one-time routine HIV screen at age 25, after the peak of incidence, would optimize clinical outcomes and be cost-effective compared with current U.S. screening practices. Focusing screening on AYA ages 18 or younger is a less efficient use of a one-time screen among AYA than screening at a later age.

The Department of Health and Human Services recommends drug resistance testing at linkage to HIV care. Because receipt and timing of testing are not well characterized, we examined testing patterns among persons with diagnosed HIV who are linked to care. Using surveillance data in six jurisdictions for persons aged ≥13 years with HIV infection diagnosed in 2013, we assessed the proportion receiving testing, and among these, the proportion receiving testing at linkage. Multivariable log-binomial regression modeling estimated associations between selected characteristics and receipt of testing (1) overall, and (2) at linkage among those tested. Of 9,408 persons linked to care, 66% received resistance testing, among whom 68% received testing at linkage. Less testing was observed among male persons who inject drugs (PWID), compared with men who have sex with men (adjusted prevalence ratio [aPR]: 0.88; 95% confidence interval [CI]: 0.81-0.97) and persons living in areas with population <500,000 compared with those in areas with population ≥2,500,000 (aPR: 0.88; CI: 0.84-0.93). In certain jurisdictions, testing was lower for persons with initial CD4 counts ≥500 cells/mm3, compared with those with CD4 counts <200 cells/mm3 (aPR range: 0.80-0.85). Of those tested, testing at linkage was lower among male PWID (aPR: 0.85; CI: 0.75-0.95) and, in some jurisdictions, persons with CD4 counts ≥500 cells/mm3 (aPR range: 0.63-0.73). Two-thirds of persons with diagnosed HIV who were linked to care received resistance testing, and most received testing at linkage as recommended. Improving receipt and timing of testing among male PWID, persons in less populous settings, and in all jurisdictions, regardless of CD4 count, may improve care outcomes.