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