HIV population-level adaptation can rapidly diminish the impact of a partially effective vaccine

Herbeck, Joshua T.; Peebles, Kathryn; Edlefsen, Paul T.; Rolland, Morgane; Murphy, James T.; Gottlieb, Geoffrey S.; Abernethy, Neil F.; Mullins, James I.; Mittler, John E.; Goodreau, Steven M.

doi:10.1016/j.vaccine.2017.12.004

Cited by 15 publications

(17 citation statements)

References 48 publications

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“…2016 ), along with behaviors that impact transmission potential at different stages, such as the timing of coital cessation during AIDS. Our base model, using only data-derived parameters, generated incident MSPVL of 4.7, consistent with previous models that share some similarities ( Herbeck et al. 2018 ).…”

Section: Discussionsupporting

confidence: 86%

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Relational concurrency, stages of infection, and the evolution of HIV set point viral load

Goodreau

Stansfield

Murphy³

et al. 2018

Virus Evolution

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HIV viral load (VL) predicts both transmission potential and rate of disease progression. For reasons that are still not fully understood, the set point viral load (SPVL) established after acute infection varies across individuals and populations. Previous studies have suggested that population mean SPVL (MSPVL) has evolved near an optimum that reflects a trade-off between transmissibility and host survival. Sexual network structures affect rates of potential exposure during different within-host phases of infection marked by different transmission probabilities, and thus affect the number and timing of transmission events. These structures include relational concurrency, which has been argued to explain key differences in HIV burden across populations. We hypothesize that concurrency will alter the fitness landscape for SPVL in ways that differ from other network features whose impacts accrue at other times during infection. To quantitatively test this hypothesis, we developed a dynamic, stochastic, data-driven network model of HIV transmission, and evolution to assess the impact of key sexual network phenomena on MSPVL evolution. Experiments were repeated in sensitivity runs that made different assumptions about transmissibility during acute infection, SPVL heritability, and the functional form of the relationship between VL and transmissibility. For our main transmission model, scenarios yielded MSPVLs ranging from 4.4 to 4.75 log10 copies/ml, covering much of the observed empirical range. MSPVL evolved to be higher in populations with high concurrency and shorter relational durations, with values varying over a clinically significant range. In linear regression analyses on these and other predictors, main effects were significant (P < 0.05), as were interaction terms, indicating that effects are interdependent. We also noted a strong correlation between two key emergent properties measured at the end of the simulations—MSPVL and HIV prevalence—most clearly for phenomena that affect transmission networks early in infection. Controlling for prevalence, high concurrency yielded higher MSPVL than other network phenomena. Interestingly, we observed lower prevalence in runs in which SPVL heritability was zero, indicating the potential for viral evolution to exacerbate disease burden over time. Future efforts to understand empirical variation in MSPVL should consider local HIV burden and basic sexual behavioral and network structure.

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Section: Discussionsupporting

confidence: 86%

“…We adapted a stochastic, dynamic, agent-, and network-based model that builds on model components, code and parametrizations previously described (see MSM model in Herbeck et al. 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Relational concurrency, stages of infection, and the evolution of HIV set point viral load

Goodreau

Stansfield

Murphy³

et al. 2018

Virus Evolution

View full text Add to dashboard Cite

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“…Moreover, it could not account for the fact that transmissions are a linked system: changes in VL in one generation of transmission changes the source VLs for the next. To explicitly address these points in a more realistic and empirically-parameterized context, we extended a stochastic, dynamic, network-based model described previously (Herbeck et al, 2018). This code builds upon the EpiModel (Jenness et al, 2016a) and statnet (Handcock et al, 2008, 2016) R packages and is available at github/EvoNetHIV/RoleSPVL.…”

Section: Methodsmentioning

confidence: 99%

“…VL varied continuously through time, following a set of parameters described in the Supplement (section S6) and in Herbeck et al (2018). We modeled four CD4+ cell categories, with transition times dependent on SPVL; CD4+ cell category governed progression and mortality.…”

Section: Methodsmentioning

confidence: 99%

Sexual role and HIV-1 set point viral load among men who have sex with men

et al. 2019

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“…We used the Evonet_HIV package (https://github.com/EvoNetHIV), a stochastic, agent-based HIV epidemic model that accounts for a broad set of virological, immunological, behavioral, and epidemiological phenomena [33–35]. Each agent has attributes such as age, sex, HIV status, viral load, CD4 count (discretized into 5 bins), and HIV diagnosis status.…”

Section: Methodsmentioning

confidence: 99%

Large benefits to youth-focused HIV treatment-as-prevention efforts in generalized heterosexual populations: An agent-based simulation model

et al. 2019

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Predominantly heterosexual HIV-1 epidemics like those in sub-Saharan Africa continue to have high HIV incidence in young people. We used a stochastic, agent-based model for age-disparate networks to test the hypothesis that focusing uptake and retention of ART among youth could enhance the efficiency of treatment as prevention (TasP) campaigns. We used the model to identify strategies that reduce incidence to negligible levels (i.e., < 0.1 cases/100 person-years) 20–25 years after initiation of a targeted TasP campaign. The model was parameterized using behavioral, demographic, and clinical data from published papers and national reports. To keep a focus on the underlying age effects we model a generalized heterosexual population with average risks (i.e., no MSM, no PWIDs, no sex workers) and no entry of HIV+ people from other regions. The model assumes that most people (default 95%, range in variant simulations 60–95%) are “linkable”; i.e., could get linked to effective care given sufficient resources. To simplify the accounting, we assume a rapid jump in the number of people receiving treatment at the start of the TasP campaign, followed by a 2% annual increase that continues until all linkable HIV+ people have been treated. Under historical scenarios of CD4-based targeted ART allocation and current policies of untargeted (random) ART allocation, our model predicts that viral replication would need to be suppressed in 60–85% of infected people at the start of the TasP campaign to drive incidence to negligible levels. Under age-based strategies, by contrast, this percentage dropped by 18–54%, depending on the strength of the epidemic and the age target. For our baseline model, targeting those under age 30 halved the number of people who need to be treated. Age-based targeting also minimized total and time-discounted AIDS deaths over 25 years. Age-based targeting yielded benefits without being highly exclusive; in a model in which 60% of infected people were treated, ~87% and ~58% of those initiating therapy during a campaign targeting those <25 and <30 years, respectively, fell outside the target group. Sensitivity analyses revealed that youth-focused TasP is beneficial due to age-related risk factors (e.g. shorter relationship durations), and an age-specific herd immunity (ASHI) effect that protects uninfected adolescents entering the sexually active population. As testing rates increase in response to UNAIDS 90-90-90 goals, efforts to link all young people to care and treatment could contribute enormously to ending the HIV epidemic.

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HIV population-level adaptation can rapidly diminish the impact of a partially effective vaccine

Abstract: These findings suggest that approaches to HIV vaccine development, program implementation, and epidemic modeling may require attention to viral adaptation in response to vaccination.

Cited by 15 publications

References 48 publications

Relational concurrency, stages of infection, and the evolution of HIV set point viral load

Relational concurrency, stages of infection, and the evolution of HIV set point viral load

Sexual role and HIV-1 set point viral load among men who have sex with men

Large benefits to youth-focused HIV treatment-as-prevention efforts in generalized heterosexual populations: An agent-based simulation model

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