Epidemiology of HIV among American Indians and Alaska Natives – United States, 2008-2011

American Indians/Alaska Natives (AI/AN) diagnosed with HIV infection have poorer survivorship and a higher percentage of Stage 3 (AIDS] diagnoses within one year of HIV diagnosis, compared to most race/ethnicity groups. National HIV surveillance data for 2008-2011 were used to determine diagnosis rates of HIV infection, persons living with HIV, and persons with a late diagnosis (Stage 3 within three months of HIV diagnosis) by selected characteristics for AI/AN and a combined other race/ethnicity group. The highest percentages of 862 AI/AN diagnosed with HIV infection were among males (75.7%), AI/AN aged 25-34 years (32.9%), persons living in large metropolitan areas (53.4%), and those diagnosed in outpatient facilities (39.4%). Among males, the majority of infections were attributed to male-to-male sexual contact (MSM) (71.8%). The percentage of infections attributed to injection drug use (IDU) for AI/AN females (28.5%) was greater than the other race/ethnicity group (15.2%). Probability of late diagnosis among AI/AN males was associated with: age \u3e35 years, and diagnosis in emergency room or hospital, or outpatient settings, and among AI/AN females, diagnosis in hospital or emergency room. Early detection of HIV infection along with linkage to and retention in care are important for all populations, including AI/AN. Routine HIV screening at a variety of public health and outpatient facilities, and linkage to care are important to decrease HIV transmission and improve survival

Natural selection favoring more transmissible HIV detected in United States molecular transmission network.

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

Incident infection in high-priority HIV molecular transmission clusters in the United States.

ObjectiveTo identify correlates of incident HIV infection in rapidly growing HIV molecular clusters.DesignPhylogenetic analysis of HIV public health surveillance data.MethodsHigh-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 three 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.ResultsOf 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.ConclusionThese 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

Maintenance and reappearance of extremely divergent intra-host HIV-1 variants.

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

Using Molecular HIV Surveillance Data to Understand Transmission Between Subpopulations in 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 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

Transmission fitness of drug-resistant HIV revealed in a surveillance system transmission network

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

Natural selection favoring more transmissible HIV detected in United States molecular transmission network.

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 fitness of drug-resistant HIV revealed in a surveillance system transmission network.

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 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