Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: Wertheim JO [original query] |
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Recommendations on data sharing in HIV drug resistance research
Inzaule SC , Siedner MJ , Little SJ , Avila-Rios S , Ayitewala A , Bosch RJ , Calvez V , Ceccherini-Silberstein F , Charpentier C , Descamps D , Eshleman SH , Fokam J , Frenkel LM , Gupta RK , Ioannidis JPA , Kaleebu P , Kantor R , Kassaye SG , Kosakovsky Pond SL , Kouamou V , Kouyos RD , Kuritzkes DR , Lessells R , Marcelin AG , Mbuagbaw L , Minalga B , Ndembi N , Neher RA , Paredes R , Pillay D , Raizes EG , Rhee SY , Richman DD , Ruxrungtham K , Sabeti PC , Schapiro JM , Sirivichayakul S , Steegen K , Sugiura W , van Zyl GU , Vandamme AM , Wensing AMJ , Wertheim JO , Gunthard HF , Jordan MR , Shafer RW . PLoS Med 2023 20 (9) e1004293 Author summary • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV. |
Increasing Capacity to Detect Clusters of Rapid HIV Transmission in Varied Populations-United States.
Oster AM , Panneer N , Lyss SB , McClung RP , Watson M , Saduvala N , Ocfemia MCB , Linley L , Switzer WM , Wertheim JO , Campbell E , Hernandez AL , France AM . Viruses 2021 13 (4) 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. |
Addressing ethical challenges in US-based HIV phylogenetic research.
Dawson L , Benbow N , Fletcher FE , Kassaye S , Killelea A , Latham SR , Lee LM , Leitner T , Little SJ , Mehta SR , Martinez O , Minalga B , Poon A , Rennie S , Sugarman J , Sweeney P , Torian LV , Wertheim JO . J Infect Dis 2020 222 (12) 1997-2006 In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials; in molecular epidemiology; and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in United States-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) community engagement; (4) legal issues; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research. |
Incident infection in high-priority HIV molecular transmission clusters in the united states.
Wertheim JO , Panneer N , France AM , Saduvala N , Oster AM . AIDS 2020 34 (8) 1187-1193 OBJECTIVE: To identify correlates of incident HIV infection in rapidly growing HIV molecular clusters. DESIGN: Phylogenetic analysis of HIV public health surveillance data. METHODS: High-priority HIV genetic transmission clusters with evidence of rapid growth in 2012 (i.e., clusters with a pairwise genetic distance </=0.005 substitutions/site and at least 3 cases diagnosed in 2012) were identified using HIV-TRACE. Then, we investigated cluster growth, defined as HIV cases diagnosed in the following 5 years that were genetically linked to these clusters. For clusters that grew during the follow-up period, Bayesian molecular clock phylogenetic inference was performed to identify clusters with evidence of incident HIV infection (as opposed to diagnosis of previously infected cases) during this follow-up period. RESULTS: Of the 116 rapidly growing clusters identified, 73 (63%) had phylogenetic evidence for an incident HIV case during the 5-year follow-up period. Correlates of an incident HIV case arising in clusters included a greater number of diagnosed but virally unsuppressed cases in 2012, a greater number of inferred undiagnosed cases in the cluster in 2012, and a younger time of most recent common ancestor for the cluster. CONCLUSIONS: These findings suggest that incident infections in rapidly growing clusters originate equally from diagnosed but unsuppressed cases and undiagnosed infections. These results highlight the importance of promoting retention in care and viral suppression as well as partner notification and other case-finding activities when investigating and intervening on high-priority molecular transmission clusters. |
Temporal Changes in HIV Transmission Patterns among Young Men Who Have Sex with Men, United States, 2009-2016.
Panneer N , France AM , Whiteside YO , Zhang T , Wertheim JO , Oster AM . J Acquir Immune Defic Syndr 2020 84 (1) 1-4 BACKGROUND: In the United States (U.S.), young (aged 13-24 years) men who have sex with men (MSM) bear a disproportionate burden of HIV. Transmission among MSM has been found to be disassortative by age. METHODS: We analyzed HIV-1 pol sequences reported to the U.S. National HIV Surveillance System from MSM with HIV diagnosed during 2009-2016. Using an HIV genetic transmission network, we identified persons with closely related viruses (i.e., genetic distance </=1.5%) and used multivariable logistic regression to examine changes from 2009-2012 to 2013-2016 in proportions of MSM linked to young MSM who were > 5 years older or of the same race/ethnicity. RESULTS: Among 9,510 young MSM linked to another MSM with a closely related virus, 37% linked to an older MSM and 62% linked to a MSM of the same race/ethnicity. Comparing 2013-2016 with 2009-2012, we found increases in linkage of older MSM to young MSM, with the most substantial increases seen in Hispanic/Latinos aged 13-19 (adjusted prevalence ratio [APR]=1.31, 95% confidence interval [CI]=1.11-1.56) and blacks aged 13-19 (APR=1.23, CI=1.06-1.41) and 20-24 (APR=1.14, CI=1.02-1.28). In contrast, change in linkage patterns among racial/ethnic groups was unremarkable. CONCLUSIONS: We found evidence of increased age mixing among MSM with respect to HIV transmission over time, which coincides temporally with changes in partner-seeking behavior such as increased use of mobile applications. These findings indicate the importance of social factors on HIV sexual and transmission networks and suggest that prevention efforts need to effectively reach MSM of all ages. |
Natural selection favoring more transmissible HIV detected in United States molecular transmission network.
Wertheim JO , Oster AM , Switzer WM , Zhang C , Panneer N , Campbell E , Saduvala N , Johnson JA , Heneine W . Nat Commun 2019 10 (1) 5788 HIV molecular epidemiology can identify clusters of individuals with elevated rates of HIV transmission. These variable transmission rates are primarily driven by host risk behavior; however, the effect of viral traits on variable transmission rates is poorly understood. Viral load, the concentration of HIV in blood, is a heritable viral trait that influences HIV infectiousness and disease progression. Here, we reconstruct HIV genetic transmission clusters using data from the United States National HIV Surveillance System and report that viruses in clusters, inferred to be frequently transmitted, have higher viral loads at diagnosis. Further, viral load is higher in people in larger clusters and with increased network connectivity, suggesting that HIV in the United States is experiencing natural selection to be more infectious and virulent. We also observe a concurrent increase in viral load at diagnosis over the last decade. This evolutionary trajectory may be slowed by prevention strategies prioritized toward rapidly growing transmission clusters. |
Transmission patterns in a low HIV-morbidity state - Wisconsin, 2014-2017
Grande KM , Schumann CL , Banez Ocfemia MC , Vergeront JM , Wertheim JO , Oster AM . MMWR Morb Mortal Wkly Rep 2019 68 (6) 149-152 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. |
Maintenance and reappearance of extremely divergent intra-host HIV-1 variants.
Wertheim JO , Oster AM , Murrell B , Saduvala N , Heneine W , Switzer WM , Johnson JA . Virus Evol 2018 4 (2) vey030 Understanding genetic variation in human immunodeficiency virus (HIV) is clinically and immunologically important for patient treatment and vaccine development. We investigated the longitudinal intra-host genetic variation of HIV in over 3,000 individuals in the US National HIV Surveillance System with at least four reported HIV-1 polymerase (pol) sequences. In this population, we identified 149 putative instances of superinfection (i.e. an individual sequentially infected with genetically divergent, polyphyletic viruses). Unexpectedly, we discovered a group of 240 individuals with consecutively sampled viral strains that were >0.015 substitutions/site divergent, despite remaining monophyletic in the phylogeny. Viruses in some of these individuals had a maximum genetic divergence approaching that found between two random, unrelated HIV-1 subtype-B pol sequences within the US population. Individuals with these highly divergent viruses tended to be diagnosed nearly a decade earlier in the epidemic than people with superinfection or virus with less intra-host genetic variation, and they had distinct transmission risk factor profiles. To better understand this genetic variation in cases with extremely divergent, monophyletic viruses, we performed molecular clock phylogenetic analysis. Our findings suggest that, like Hepatitis C virus, extremely divergent HIV lineages can be maintained within an individual and reemerge over a period of years. |
Identifying Clusters of Recent and Rapid HIV Transmission Through Analysis of Molecular Surveillance Data.
Oster AM , France AM , Panneer N , Banez Ocfemia MC , Campbell E , Dasgupta S , Switzer WM , Wertheim JO , Hernandez AL . J Acquir Immune Defic Syndr 2018 79 (5) 543-550 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 two genetic distance thresholds (0.5% and 1.5%) and two time periods for diagnoses (all years and 2013-2015, i.e., 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. |
HIV Transmission Dynamics among Foreign-born Persons in the United States.
Valverde EE , Oster AM , Xu S , Wertheim JO , Hernandez AL . J Acquir Immune Defic Syndr 2017 76 (5) 445-452 BACKGROUND: In the United States (U.S.), foreign-born persons are disproportionately affected by HIV and differ epidemiologically from U.S.-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 U.S. 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. The majority of transmission partners of male foreign-born persons (63%) were born in the United States, whereas the majority of transmission partners of female foreign-born (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 U.S. should include information of the transmission networks in which these individuals acquire or transmit HIV in order to develop more targeted HIV prevention interventions. |
Transmission fitness of drug-resistant HIV revealed in a surveillance system transmission network.
Wertheim JO , Oster AM , Johnson JA , Switzer WM , Saduvala N , Hernandez AL , Hall HI , Heneine W . Virus Evol 2017 3 (1) vex008 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-naive 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-naive 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. |
Increasing HIV-1 subtype diversity in seven states, United States, 2006-2013.
Oster AM , Switzer WM , Hernandez AL , Saduvala N , Wertheim JO , Nwangwu-Ike N , Ocfemia MC , Campbell E , Hall HI . Ann Epidemiol 2017 27 (4) 244-251 e1 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.
Wertheim JO , Oster AM , Hernandez AL , Saduvala N , Banez Ocfemia MC , Hall I . AIDS Res Hum Retroviruses 2016 32 1046-1053 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 analysis indicates that introduced non-subtype B infections have resulted in onward transmission within the United States. |
Molecular analysis allows inference into HIV transmission among young men who have sex with men in the United States.
Whiteside YO , Song R , Wertheim JO , Oster AM . AIDS 2015 29 (18) 2517-22 OBJECTIVE: The objective of this study is to understand the spread of HIV among and between age and racial/ethnic groups of men who engage in male-to-male sexual contact (MSM) in the United States. DESIGN: An analysis of HIV-1 pol sequences for MSM collected through the US National HIV Surveillance System (NHSS) during 2001-2012. METHODS: Pairwise genetic distance was calculated to determine potential transmission partners (those with very closely related nucleotide sequences, i.e. distance ≤1.5%). We described race/ethnicity and age of potential transmission partners of MSM. RESULTS: Of 23 048 MSM with HIV sequences submitted to NHSS during 2000-2012, we identified potential transmission partners for 8880 (39%). Most potential transmission partners were of the same race/ethnicity (78% for blacks/African-Americans, 64% for whites and 49% for Hispanics/Latinos). This assortative mixing was even more pronounced in the youngest age groups. Significantly fewer young black/African-American and Hispanic/Latino MSM had older potential transmission partners than young white MSM. CONCLUSION: Black/African-American MSM, who are more profoundly affected by HIV, were more likely to have potential HIV transmission partners who were of the same race/ethnicity and similar in age, suggesting that disparities in HIV infections are in large part not due to age-disassortative relationships. Concerted efforts to increase access to preexposure prophylaxis, quality HIV care and effective treatment are needed to interrupt transmission chains among young, black/African-American MSM. |
Using Molecular HIV Surveillance Data to Understand Transmission Between Subpopulations in the United States.
Oster AM , Wertheim JO , Hernandez AL , Banez Ocfemia MC , Saduvala N , Hall HI . J Acquir Immune Defic Syndr 2015 70 (4) 444-51 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 U.S. 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%) linked to ≥1 other sequence. Of men who have sex with men (MSM) who 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% 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 U.S. 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. |
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