Transmitted Drug Resistance Among Human Immunodeficiency Virus (HIV)-1 Diagnoses in the United States, 2014-2018.

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.

HIV Cluster and Outbreak Detection and Response: The Science and Experience.

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.

Increasing Capacity to Detect Clusters of Rapid HIV Transmission in Varied Populations-United States.

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.

Characteristics and Care Outcomes Among Persons Living With Perinatally Acquired HIV Infection in the United States, 2015.

BACKGROUND: Medical advancements have improved the survival of persons with perinatally acquired HIV infection (PHIV). We describe persons living with diagnosed PHIV and assess receipt of HIV care, retention in care, and viral suppression. METHODS: Data reported to the National HIV Surveillance System through December 2017 were used to characterize persons living with diagnosed PHIV by year-end 2015 in the United States and 6 dependent areas. National HIV Surveillance System data from 40 jurisdictions with complete laboratory reporting were used to assess receipt of HIV care (≥1 CD4 or viral load during 2015), retention in HIV care (≥2 CD4 or viral load tests ≥3 months apart during 2015) and viral suppression (<200 copies/mL during 2015) among persons with PHIV diagnosed by year-end 2014 and alive at year-end 2015. RESULTS: By year-end 2015, 11,747 persons were living with PHIV and half were aged 18-25 years. Of 9562 persons with HIV diagnosed by year-end 2014 and living with PHIV at year-end 2015 in the 40 jurisdictions, 75.4% received any care, 61.1% were retained in care, and 49.0% achieved viral suppression. Persons aged ≤17 years had a significantly higher prevalence of being retained in care (prevalence ratio = 1.2, 95% confidence interval = 1.2 to 1.3) and virally suppressed (prevalence ratio = 1.4, 95% confidence interval = 1.3 to 1.5) than persons aged 18-25 years. CONCLUSIONS: Efforts to improve care outcomes among persons with PHIV are needed. Enhanced collaboration between pediatric and adult medical providers may ensure continuity of care during the transition from adolescence to adulthood.

Transmission Patterns in a Low HIV-Morbidity State - Wisconsin, 2014-2017.

Public health interviews (i.e., partner services), during which persons with diagnosed human immunodeficiency virus (HIV) infection name their sexual or needle-sharing partners (named partners), are used to identify HIV transmission networks to guide and prioritize HIV prevention activities. HIV sequence data, generated from provider-ordered drug resistance testing, can be used to understand characteristics of molecular clusters, a group of sequences for which each sequence is highly similar (linked) to all other sequences, and assess whether named partners are plausible HIV transmission partners. Although molecular data in higher HIV-morbidity states have been analyzed (1-3), few analyses exist for lower morbidity states (4), such as Wisconsin, which reported 4.6 HIV diagnoses per 100,000 persons aged ≥13 years in 2016 (5). The Wisconsin Division of Public Health (DPH) analyzed HIV sequence data generated from provider-ordered drug resistance testing and collected through routine HIV surveillance to identify molecular clusters and describe demographic and transmission risk characteristics among pairs of persons whose sequences were highly genetically similar (i.e., molecular linkages). In addition, overlap between partner linkages identified during public health interviews and molecular linkages was assessed. Overall, characteristics of molecular clusters in Wisconsin mirrored those from states with more HIV diagnoses, particularly in that most molecular linkages were observed among persons of the same race (78.2% of non-Hispanic blacks [blacks] linked to other blacks), the same transmission risk (90.2% of men who have sex with men [MSM] linked to other MSM), and the same age group (59.2% of persons aged 20-29 years linked to other persons aged 20-29 years). Among named partner linkages identified during interviews in which both persons also had a reported sequence, overlap of named partner and molecular linkages was moderate: 33.8% of named partners were plausible transmission partners according to available molecular data. Analysis of HIV sequence data is a useful tool for characterizing transmission patterns not immediately apparent using traditional public health interview data, even in a state with lower HIV morbidity. Prevention recommendations generated from national data (e.g., targeting preexposure prophylaxis for HIV-negative persons at high risk and implementing measures to maintain viral suppression among persons with HIV infection) also are relevant in a lower HIV-morbidity state.

Identifying Clusters of Recent and Rapid HIV Transmission Through Analysis of Molecular Surveillance Data.

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.

A programmatic approach to address increasing HIV diagnoses among Hispanic/Latino MSM, 2010-2014.

From 2010 to 2015, young (13-24 years) Hispanic/Latino gay, bisexual and other men who have sex with men (MSM) experienced the largest increase (18%) in numbers of HIV diagnoses among all racial/ethnic groups. In 2016, the Centers for Disease Control and Prevention (CDC) assembled a team of scientists and public health analysts to develop a programmatic approach for addressing the increasing HIV diagnosis among Hispanic/Latino MSM. The team used a data driven review process, i.e., comprehensive review of surveillance, epidemiologic, and programmatic data, to explore key questions from the literature on factors associated with HIV diagnoses among Hispanic/Latino MSM and to inform the approach. This paper describes key findings from the review and discusses the approach. The approach includes the following activities: increase awareness and support testing by expanding existing campaigns targeting Hispanic/Latino MSM to jurisdictions where diagnoses are increasing; strengthen existing efforts that support treatment as prevention and increase engagement in care and viral suppression among Hispanic/Latino MSM living with HIV and promote prevention, e.g., PrEP uptake and condom use, among Hispanic/Latino MSM who are at high-risk for HIV infection.

HIV Diagnoses Among Persons Aged 13-29 Years - United States, 2010-2014.

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.

The Optimal Age for Screening Adolescents and Young Adults Without Identified Risk Factors for HIV.

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.

Receipt and timing of HIV drug resistance testing in six U.S. jurisdictions.

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.

Use of Blood Donor Screening Data to Estimate Zika Virus Incidence, Puerto Rico, April-August 2016.

Puerto Rico has been heavily impacted by Zika virus, a mosquitoborne flavivirus that emerged in the Americas during 2015. Although most persons with Zika virus show no symptoms, the virus can cause neurologic and other complications, including fetal microcephaly. Local Zika virus transmission in Puerto Rico has been reported since December 2015. To prevent transfusion-associated transmission, local blood collection ceased in March 2016 but resumed in April 2016 after Zika virus screening of blood donations became available. Using data from screening of blood donations collected by the 2 largest blood centers in Puerto Rico during April 3-August 12, 2016, and assuming a 9.9-day duration of viremia, we estimated that 469,321 persons in Puerto Rico were infected during this period, for an estimated cumulative incidence of 12.9%. Results from blood donation screening during arboviral outbreaks can supplement routine clinical and surveillance data for improved targeting of prevention efforts.

Increasing HIV-1 subtype diversity in seven states, United States, 2006-2013.

PURPOSE: The aim of the analysis was to explore HIV-1 subtype diversity in the United States and understand differences in prevalence of non-B subtypes and circulating recombinant forms (CRFs) between demographic/risk groups and over time. METHODS: We included HIV-1 polymerase sequences reported to the National HIV Surveillance System for HIV infections diagnosed during 2006-2013 in seven states. We assigned subtype or CRF using the automated subtyping tool COMET, assessed subtype/CRF prevalence by demographic characteristics and country of birth, and determined changes in subtype/CRF by HIV diagnosis year. RESULTS: Of 32,968 sequences, 30,757 (93.3%) were subtype B. The most common non-B subtypes and CRFs were C (1.6%), CRF02_AG (1.4%), A (0.6%), CRF01_AE (0.5%), and G (0.3%). Elevated percentages of non-B infections occurred among persons aged <13 years at diagnosis (40.9%), Asians (32.1%), persons born outside the United States (22.6%), and persons with infection attributable to heterosexual contact (12.0%-15.0%). Prevalence of non-B infections increased from 5.9% in 2006 to 8.5% in 2013. CONCLUSIONS: Subtype B continues to predominate in the United States. However, the percentage of non-B infections has grown in recent years, and numerous demographic subgroups have much higher prevalence. Subgroups and areas with high prevalence of non-B infections might represent sub-epidemics meriting further investigation.

The International Dimension of the U.S. HIV Transmission Network and Onward Transmission of HIV Recently Imported into the United States.

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.

Young Sexual Minority Males in the United States: Sociodemographic Characteristics And Sexual Attraction, Identity and Behavior.

CONTEXT: HIV incidence is increasing among 13-24-year-old U.S. men who have sex with men, yet limited research is available to guide HIV prevention efforts for this population. METHODS: National Survey of Family Growth data collected in 2002, in 2006-2010 and in 2011-2013 from 8,068 males aged 15-24 were analyzed to describe the population of U.S. young sexual minority males (i.e., males reporting same-sex attraction, identity or behavior). Correlates of sexual minority classification were assessed in logistic regression models. RESULTS: An estimated 10% of young males, representing a population of 2.1 million, were sexual minorities. Males had an elevated likelihood of being sexual minorities if they were aged 18-19 or 20-24, rather than 15-17 (prevalence ratio, 1.7 for each); belonged to nonblack, non-Hispanic racial or ethnic minority groups (1.6); had no religious affiliation, rather than considering religion very important (1.9); or lived below the federal poverty level (1.3). They had a reduced likelihood of being sexual minorities if they lived in metropolitan areas outside of central cities (0.7). Among young sexual minority males, 44% were 15-19 years old, 29% were poor and 59% resided outside central cities. Forty-seven percent had engaged in same-sex behavior. Of those with data on all measured dimensions of sexuality, 24% reported same-sex attraction, identity and behavior; 22% considered themselves heterosexual, yet had had a male sex partner. CONCLUSION: Future investigations can further explore subpopulations of young sexual minority males and assess sexual trajectories, resilience and HIV risk.

The status of the National HIV Surveillance System, United States, 2013.

The burden of HIV disease in the United States is monitored by using a comprehensive surveillance system. Data from this system are used at the federal, state, and local levels to plan, implement, and evaluate public health policies and programs. Implementation of HIV reporting has differed by area, and for the first time in early 2013, estimated data on diagnosed HIV infection were available from all 50 states, the District of Columbia, and six U.S. dependent areas. The newly available data for the entire U.S. as well as several other key changes to the surveillance system support the need to provide an updated summary of the status of the National HIV Surveillance System.

Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008.

BACKGROUND: Most sexually active people will be infected with a sexually transmitted infection (STI) at some point in their lives. The number of STIs in the United States was previously estimated in 2000. We updated previous estimates to reflect the number of STIs for calendar year 2008. METHODS: We reviewed available data and literature and conservatively estimated incident and prevalent infections nationally for 8 common STIs: chlamydia, gonorrhea, syphilis, herpes, human papillomavirus, hepatitis B, HIV, and trichomoniasis. Where available, data from nationally representative surveys such as the National Health and Nutrition Examination Survey were used to provide national estimates of STI prevalence or incidence. The strength of each estimate was rated good, fair, or poor, according to the quality of the evidence. RESULTS: In 2008, there were an estimated 110 million prevalent STIs among women and men in the United States. Of these, more than 20% of infections (22.1 million) were among women and men aged 15 to 24 years. Approximately 19.7 million incident infections occurred in the United States in 2008; nearly 50% (9.8 million) were acquired by young women and men aged 15 to 24 years. Human papillomavirus infections, many of which are asymptomatic and do not cause disease, accounted for most of both prevalent and incident infections. CONCLUSIONS: Sexually transmitted infections are common in the United States, with a disproportionate burden among young adolescents and adults. Public health efforts to address STIs should focus on prevention among at-risk populations to reduce the number and impact of STIs.

Emergency survey methods in acute cryptosporidiosis outbreak.

In August 2003, a communitywide outbreak of cryptosporidiosis occurred in Kansas. We conducted a case-control study to assess risk factors associated with Cryptosporidium infection by using the telephone survey infrastructure of the Behavioral Risk Factor Surveillance System. Using existing state-based infrastructure provides an innovative means for investigating acute outbreaks.