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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.

BackgroundDetecting recent and rapid spread of HIV can help prioritize prevention and early treatment for those at highest risk of transmission. HIV genetic sequence data can identify transmission clusters, but previous approaches have not distinguished clusters of recent, rapid transmission. We assessed an analytic approach to identify such clusters in the United States.MethodsWe analyzed 156,553 partial HIV-1 polymerase sequences reported to the National HIV Surveillance System and inferred transmission clusters using 2 genetic distance thresholds (0.5% and 1.5%) and 2 periods for diagnoses (all years and 2013-2015, ie, recent diagnoses). For rapidly growing clusters (with ≥5 diagnoses during 2015), molecular clock phylogenetic analysis estimated the time to most recent common ancestor for all divergence events within the cluster. Cluster transmission rates were estimated using these phylogenies.ResultsA distance threshold of 1.5% identified 103 rapidly growing clusters using all diagnoses and 73 using recent diagnoses; at 0.5%, 15 clusters were identified using all diagnoses and 13 using recent diagnoses. Molecular clock analysis estimated that the 13 clusters identified at 0.5% using recent diagnoses had been diversifying for a median of 4.7 years, compared with 6.5-13.2 years using other approaches. The 13 clusters at 0.5% had a transmission rate of 33/100 person-years, compared with previous national estimates of 4/100 person-years.ConclusionsOur approach identified clusters with transmission rates 8 times those of previous national estimates. This method can identify groups involved in rapid transmission and help programs effectively direct and prioritize limited public health resources.

BackgroundIn the United States (US), foreign-born persons are disproportionately affected by HIV and differ epidemiologically from US-born persons with diagnosed HIV infection. Understanding HIV transmission dynamics among foreign-born persons is important to guide HIV prevention efforts for these populations. We conducted molecular transmission network analysis to describe HIV transmission dynamics among foreign-born persons with diagnosed HIV.MethodsUsing HIV-1 polymerase nucleotide sequences reported to the US National HIV Surveillance System for persons with diagnosed HIV infection during 2001-2013, we constructed a genetic distance-based transmission network using HIV-TRACE and examined the birth region of potential transmission partners in this network.ResultsOf 77,686 people, 12,064 (16%) were foreign born. Overall, 28% of foreign-born persons linked to at least one other person in the transmission network. Of potential transmission partners, 62% were born in the United States, 31% were born in the same region as the foreign-born person, and 7% were born in another region of the world. Most transmission partners of male foreign-born persons (63%) were born in the United States, whereas most transmission partners of female foreign-borns (57%) were born in their same world region.DiscussionThese finding suggests that a majority of HIV infections among foreign-born persons in our network occurred after immigrating to the United States. Efforts to prevent HIV infection among foreign-born persons in the United States should include information of the transmission networks in which these individuals acquire or transmit HIV to develop more targeted HIV prevention interventions.

Test-and-treat programs are central to the global control of HIV, but transmitted drug resistance threatens the effectiveness of these programs. HIV mutations conferring resistance to antiretroviral drugs reduce replicative fitness in vitro, but their effect on propagation in vivo is less understood. Here, we estimate transmission fitness of these mutations in antiretroviral-naïve populations in the U.S. National HIV Surveillance System by comparing their frequency of clustering in a genetic transmission network relative with wild-type viruses. The large dataset (66,221 persons), comprising 30,196 antiretroviral-naïve persons, permitted the evaluation of sixty-nine resistance mutations. Decreased transmission fitness was demonstrated for twenty-three mutations, including M184V. In contrast, many high prevalence mutations (e.g. K103N, Y181C, and L90M) had transmission fitness that was indistinguishable from or exceeded wild-type fitness, permitting the establishment of large, self-sustaining drug resistance reservoirs. We highlight implications of these findings on strategies to preserve global treatment effectiveness.

The majority of HIV infections in the United States can be traced back to a single introduction in late 1960s or early 1970s. However, it remains unclear whether subsequent introductions of HIV into the United States have given rise to onward transmission. Genetic transmission networks can aid in understanding HIV transmission. We constructed a genetic distance-based transmission network using HIV-1 pol sequences reported to the U.S. National HIV Surveillance System (n = 41,539) and all publicly available non-U.S. HIV-1 pol sequences (n = 86,215). Of the 13,145 U.S. persons clustered in the network, 457 (3.5%) were genetically linked to a potential transmission partner outside the United States. For internationally connected persons residing in but born outside the United States, 61% had a connection to their country of birth or to another country that shared a language with their country of birth. Bayesian molecular clock phylogenetic analyses indicate that introduced nonsubtype B infections have resulted in onward transmission within the United States.

BackgroundStudying HIV transmission networks provides insight into the spread of HIV and opportunities for intervention. We identified transmission dynamics among risk groups and racial/ethnic groups in the United States.MethodsFor HIV-1 pol sequences reported to the US National HIV Surveillance System during 2001-2012, we calculated pairwise genetic distance, identified linked pairs of sequences (those with distance ≤1.5%), and examined transmission category and race/ethnicity of these potential transmission partners.ResultsOf 40,950 sequences, 12,910 (32%) were linked to ≥1 other sequence. Of men who have sex with men (MSM) who were linked to ≥1 sequence, 88% were linked to other MSM and only 4% were linked to heterosexual women. Of heterosexual women for whom we identified potential transmission partners, 29% were linked to MSM, 21% to heterosexual men, and 12% to persons who inject drugs. Older and black MSM were more likely to be linked to heterosexual women. Assortative mixing was present for all racial/ethnic groups; 81% of blacks/African Americans linked to other blacks.ConclusionsThis analysis is the first use of US surveillance data to infer an HIV transmission network. Our data suggest that HIV infections among heterosexual women predominantly originate from MSM, followed by heterosexual men. Although few MSM were linked to women, suggesting that a minority of MSM are involved in transmission with heterosexual women, these transmissions represent a substantial proportion of HIV acquisitions by heterosexual women. Interventions that reduce transmissions involving MSM are likely to also reduce HIV acquisition among other risk groups.

The Centers for Disease Control and Prevention (CDC) and state, territorial, and local health departments have expanded efforts to detect and respond to HIV clusters and outbreaks in the United States. In July 2017, CDC created the HIV Outbreak Coordination Unit (OCU) to ensure consistent and collaborative assessment of requests from health departments for consultation or support on possible HIV clusters and outbreaks of elevated concern. The HIV OCU is a multidisciplinary, cross-organization functional unit within CDC's Division of HIV/AIDS Prevention. HIV OCU members have expertise in areas such as outbreak detection and investigation, prevention, laboratory services, surveillance and epidemiology, policy, communication, and operations. HIV OCU discussions facilitate problem solving, coordination, and situational awareness. Between HIV OCU meetings, designated CDC staff members communicate regularly with health departments to provide support and assessment. During July 2017–December 2019, the HIV OCU reviewed 31 possible HIV clusters and outbreaks (ie, events) in 22 states that were detected by CDC, health departments, or local partners; 17 events involved HIV transmission associated with injection drug use, and other events typically involved sexual transmission or overall increases in HIV diagnoses. CDC supported health departments remotely or on site with planning and prioritization; data collection, management, and analysis; communications; laboratory support; multistate coordination; and expansion of HIV prevention services. The HIV OCU has augmented CDC's support of HIV cluster and outbreak assessment and response at health departments and had important internal organizational benefits. Health departments may benefit from developing or strengthening similar units to coordinate detection and response efforts within and across public health agencies and advance the national Ending the HIV Epidemic initiative. [ABSTRACT FROM AUTHOR]

Background Transmitted human immunodeficiency virus (HIV) drug resistance can threaten the efficacy of antiretroviral therapy and pre-exposure 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 US 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, 9616 (18.9%) had ≥1 TDRM. TDRM prevalence was 0.8% for integrase strand transfer inhibitors (INSTIs), 4.2% for protease inhibitors, 6.9% for nucleoside reverse transcriptase inhibitors (NRTIs), and 12.0% for non-NRTIs. 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% confidence interval, 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 INSTIs and PrEP. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) accounted for two thirds of new HIV infections in the United States in 2019 despite representing approximately 2% of the adult population., Methods: CDC analyzed surveillance data to determine trends in estimated new HIV infections and to assess measures of undiagnosed infection and HIV prevention and treatment services including HIV testing, preexposure prophylaxis (PrEP) use, antiretroviral therapy (ART) adherence, and viral suppression, as well as HIV-related stigma., Results: The estimated number of new HIV infections among MSM was 25,100 in 2010 and 23,100 in 2019. New infections decreased significantly among White MSM but did not decrease among Black or African American (Black) MSM and Hispanic/Latino MSM. New infections increased among MSM aged 25-34 years. During 2019, approximately 83% of Black MSM and 80% of Hispanic/Latino MSM compared with 90% of White MSM with HIV had received an HIV diagnosis. The lowest percentage of diagnosed infection was among MSM aged 13-24 years (55%). Among MSM with a likely PrEP indication, discussions about PrEP with a provider and PrEP use were lower among Black MSM (47% and 27%, respectively) and Hispanic/Latino MSM (45% and 31%) than among White MSM (59% and 42%). Among MSM with an HIV diagnosis, adherence to ART and viral suppression were lower among Black MSM (48% and 62%, respectively) and Hispanic/Latino MSM (59% and 67%) compared with White MSM (64% and 74%). Experiences of HIV-related stigma among those with an HIV diagnosis were higher among Black MSM (median = 33; scale = 0-100) and Hispanic/Latino MSM (32) compared with White MSM (26). MSM aged 18-24 years had the lowest adherence to ART (45%) and the highest median stigma score (39)., Conclusion: Improving access to and use of HIV services for MSM, especially Black MSM, Hispanic/Latino MSM, and younger MSM, and addressing social determinants of health, such as HIV-related stigma, that contribute to unequal outcomes will be essential to end the HIV epidemic in the United States., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

By June 2020, Marshallese and Hispanic or Latino (Hispanic) persons in Benton and Washington counties of Arkansas had received a disproportionately high number of diagnoses of coronavirus disease 2019 (COVID-19). Despite representing approximately 19% of these counties' populations (1), Marshallese and Hispanic persons accounted for 64% of COVID-19 cases and 57% of COVID-19-associated deaths. Analyses of surveillance data, focus group discussions, and key-informant interviews were conducted to identify challenges and propose strategies for interrupting transmission of SARS-CoV-2, the virus that causes COVID-19. Challenges included limited native-language health messaging, high household occupancy, high employment rate in the poultry processing industry, mistrust of the medical system, and changing COVID-19 guidance. Reducing the COVID-19 incidence among communities that suffer disproportionately from COVID-19 requires strengthening the coordination of public health, health care, and community stakeholders to provide culturally and linguistically tailored public health education, community-based prevention activities, case management, care navigation, and service linkage., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Life expectancy for persons with human immunodeficiency virus (HIV) infection who receive recommended treatment can approach that of the general population, yet HIV remains among the 10 leading causes of death among certain populations. Using surveillance data, CDC assessed progress toward reducing deaths among persons with diagnosed HIV (PWDH)., Methods: CDC analyzed National HIV Surveillance System data for persons aged ≥13 years to determine age-adjusted death rates per 1,000 PWDH during 2010-2018. Using the International Classification of Diseases, Tenth Revision, deaths with a nonmissing underlying cause were classified as HIV-related or non-HIV-related. Temporal changes in total deaths during 2010-2018 and deaths by cause during 2010-2017 (2018 excluded because of delays in reporting), by demographic characteristics, transmission category, and U.S. Census region of residence at time of death were calculated., Results: During 2010-2018, rates of death decreased by 36.6% overall (from 19.4 to 12.3 per 1,000 PWDH). During 2010-2017, HIV-related death rates decreased 48.4% (from 9.1 to 4.7), whereas non-HIV-related death rates decreased 8.6% (from 9.3 to 8.5). Rates of HIV-related deaths during 2017 were highest by race/ethnicity among persons of multiple races (7.0) and Black/African American persons (5.6), followed by White persons (3.9) and Hispanic/Latino persons (3.9). The HIV-related death rate was highest in the South (6.0) and lowest in the Northeast (3.2)., Conclusion: Early diagnosis, prompt treatment, and maintaining access to high-quality care and treatment have been successful in reducing HIV-related deaths and remain necessary for continuing reductions in HIV-related deaths., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Detecting recent and rapid spread of HIV can help prioritize prevention and early treatment for those at highest risk of transmission. HIV genetic sequence data can identify transmission clusters, but previous approaches have not distinguished clusters of recent, rapid transmission. We assessed an analytic approach to identify such clusters in the United States., Methods: We analyzed 156,553 partial HIV-1 polymerase sequences reported to the National HIV Surveillance System and inferred transmission clusters using 2 genetic distance thresholds (0.5% and 1.5%) and 2 periods for diagnoses (all years and 2013-2015, ie, recent diagnoses). For rapidly growing clusters (with ≥5 diagnoses during 2015), molecular clock phylogenetic analysis estimated the time to most recent common ancestor for all divergence events within the cluster. Cluster transmission rates were estimated using these phylogenies., Results: A distance threshold of 1.5% identified 103 rapidly growing clusters using all diagnoses and 73 using recent diagnoses; at 0.5%, 15 clusters were identified using all diagnoses and 13 using recent diagnoses. Molecular clock analysis estimated that the 13 clusters identified at 0.5% using recent diagnoses had been diversifying for a median of 4.7 years, compared with 6.5-13.2 years using other approaches. The 13 clusters at 0.5% had a transmission rate of 33/100 person-years, compared with previous national estimates of 4/100 person-years., Conclusions: Our approach identified clusters with transmission rates 8 times those of previous national estimates. This method can identify groups involved in rapid transmission and help programs effectively direct and prioritize limited public health resources.

Non-Hispanic blacks/African Americans (blacks) represent 12% of the U.S., Population: * However, in 2014 an estimated 43% (471,500) of persons living with diagnosed and undiagnosed human immunodeficiency virus (HIV) infection were blacks (1). In 2016, blacks accounted for 44% of all new HIV diagnoses (2). Although antiretroviral therapy (ART) prescriptions among persons in HIV care increased overall from 89% in 2009 to 94% in 2013, fewer blacks than Hispanics or Latinos (Hispanics) and non-Hispanic whites (whites) were on ART and had a suppressed viral load (<200 HIV RNA copies/mL) in their most recent viral load test result (3). Blacks also might be less likely to have sustained viral suppression over time and to experience longer periods with viral loads >1,500 HIV RNA copies/mL, a level that increases the risk for transmitting HIV (4-7). National HIV Surveillance System (NHSS) data are among those used to monitor progress toward reaching the national goal of reducing health disparities. CDC analyzed NHSS data to describe sustained viral suppression and transmission risk potential by race/ethnicity. Among 651,811 persons with HIV infection diagnosed through 2013 and who were alive through 2014 in 38 jurisdictions with complete laboratory reporting, a lower percentage of blacks had sustained viral suppression (40.8%), than had Hispanics (50.1%) and whites (56.3%). Among persons who were in care (i.e., had at least one viral load test in 2014) and had not achieved sustained viral suppression in 2014, blacks experienced longer periods (52.1% of the 12-month period) with viral loads >1,500 copies/mL, than did Hispanics (47.2%) and white (40.8%). Blacks aged 13-24 years had the lowest prevalence of sustained viral suppression, a circumstance that might increase transmission risk potential. Strengthening interventions that improve access to ART, promote adherence, and address barriers to clinical care and supportive services for all persons with diagnosed HIV infection is important for achieving the national goal of reducing health disparities., Competing Interests: No conflicts of interest were reported.

Background: In the United States (US), foreign-born persons are disproportionately affected by HIV and differ epidemiologically from US-born persons with diagnosed HIV infection. Understanding HIV transmission dynamics among foreign-born persons is important to guide HIV prevention efforts for these populations. We conducted molecular transmission network analysis to describe HIV transmission dynamics among foreign-born persons with diagnosed HIV., Methods: Using HIV-1 polymerase nucleotide sequences reported to the US National HIV Surveillance System for persons with diagnosed HIV infection during 2001-2013, we constructed a genetic distance-based transmission network using HIV-TRACE and examined the birth region of potential transmission partners in this network., Results: Of 77,686 people, 12,064 (16%) were foreign born. Overall, 28% of foreign-born persons linked to at least one other person in the transmission network. Of potential transmission partners, 62% were born in the United States, 31% were born in the same region as the foreign-born person, and 7% were born in another region of the world. Most transmission partners of male foreign-born persons (63%) were born in the United States, whereas most transmission partners of female foreign-borns (57%) were born in their same world region., Discussion: These finding suggests that a majority of HIV infections among foreign-born persons in our network occurred after immigrating to the United States. Efforts to prevent HIV infection among foreign-born persons in the United States should include information of the transmission networks in which these individuals acquire or transmit HIV to develop more targeted HIV prevention interventions.

Background: Persons unaware of their human immunodeficiency virus (HIV) infection account for approximately 40% of ongoing transmissions in the United States. Persons are unaware of their infection because of delayed HIV diagnoses that represent substantial missed opportunities to improve health outcomes and prevent HIV transmission., Methods: Data from CDC's National HIV Surveillance System were used to estimate, among persons with HIV infection diagnosed in 2015, the median interval (and range) from infection to diagnosis (diagnosis delay), based on the first CD4 test after HIV diagnosis and a CD4 depletion model indicating disease progression and, among persons living with HIV in 2015, the percentage with undiagnosed infection. Data from CDC's National HIV Behavioral Surveillance were analyzed to determine the percentage of persons at increased risk for HIV infection who had tested in the past 12 months and who had missed opportunities for testing., Results: An estimated 15% of persons living with HIV in 2015 were unaware of their infection. Among the 39,720 persons with HIV infection diagnosed in 2015, the estimated median diagnosis delay was 3.0 years (interquartile range = 0.7-7.8 years); diagnosis delay varied by race/ethnicity (from 2.2 years among whites to 4.2 years among Asians) and transmission category (from 2.0 years among females who inject drugs to 4.9 years among heterosexual males). Among persons interviewed through National HIV Behavioral Surveillance, 71% of men who have sex with men, 58% of persons who inject drugs, and 41% of heterosexual persons at increased risk for HIV infection reported testing in the past 12 months. In each risk group, at least two thirds of persons who did not have an HIV test had seen a health care provider in the past year., Conclusions: Delayed HIV diagnoses continue to be substantial for some population groups and prevent early entry to care to improve health outcomes and reduce HIV transmission to others., Implications for Public Health Practice: Health care providers and others providing HIV testing can reduce HIV-related adverse health outcomes and risk for HIV transmission by implementing routine and targeted HIV testing to decrease diagnosis delays.

Gay, bisexual, and other men who have sex with men (MSM) continue to be the population most affected by human immunodeficiency virus (HIV) in the United States. In 2014, 81% of diagnoses of HIV infection were among adult and adolescent males, and among these, 83% of infections were attributable to male-to-male sexual contact (1). Since 2006, CDC has recommended HIV testing at least annually for sexually active MSM to foster early detection of HIV infection and prevent HIV transmission (2,3). Several initiatives and strategies during the past decade have aimed to expand HIV testing among MSM to increase early diagnosis and treatment and reduce transmission. To better understand HIV testing patterns among MSM with diagnosed HIV infection, CDC analyzed data for 2007-2013 from jurisdictions conducting HIV incidence surveillance as part of CDC's National HIV Surveillance System (NHSS). Findings from this analysis suggest that increasing percentages of MSM have had a negative HIV test during the 12 months before diagnosis (48% in 2007, 56% in 2013, among those with a known date of previous negative HIV test), indicating a trend toward increased HIV testing and earlier HIV diagnosis among persons most at risk for HIV.

Background: Studying HIV transmission networks provides insight into the spread of HIV and opportunities for intervention. We identified transmission dynamics among risk groups and racial/ethnic groups in the United States., Methods: For HIV-1 pol sequences reported to the US National HIV Surveillance System during 2001-2012, we calculated pairwise genetic distance, identified linked pairs of sequences (those with distance ≤1.5%), and examined transmission category and race/ethnicity of these potential transmission partners., Results: Of 40,950 sequences, 12,910 (32%) were linked to ≥1 other sequence. Of men who have sex with men (MSM) who were linked to ≥1 sequence, 88% were linked to other MSM and only 4% were linked to heterosexual women. Of heterosexual women for whom we identified potential transmission partners, 29% were linked to MSM, 21% to heterosexual men, and 12% to persons who inject drugs. Older and black MSM were more likely to be linked to heterosexual women. Assortative mixing was present for all racial/ethnic groups; 81% of blacks/African Americans linked to other blacks., Conclusions: This analysis is the first use of US surveillance data to infer an HIV transmission network. Our data suggest that HIV infections among heterosexual women predominantly originate from MSM, followed by heterosexual men. Although few MSM were linked to women, suggesting that a minority of MSM are involved in transmission with heterosexual women, these transmissions represent a substantial proportion of HIV acquisitions by heterosexual women. Interventions that reduce transmissions involving MSM are likely to also reduce HIV acquisition among other risk groups.