Evolutionary Dynamics of Complex Networks of HIV Drug-Resistant Strains: The Case of San Francisco

Smith, Robert J.; Okano, Justin T; Kahn, James S.; Bodine, Erin; Blower, Sally

doi:10.1126/science.1180556

Cited by 106 publications

(119 citation statements)

References 29 publications

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“…This model had been parameterized using epidemiological, clinical, and behavioral data to reflect the HIV epidemic in the MSM The black line delimits the threshold at which a PrEP intervention would have no effect on increasing the number of resistant infections; below the line the number decreases, and above the line the number increases. community in San Francisco (16). Consequently, we used the same parameter values in our current analysis as had been used in ref.…”

Section: Methodsmentioning

confidence: 99%

“…Consequently, we used the same parameter values in our current analysis as had been used in ref. 16. For completeness, we include these parameter values in the tables in SI Appendix, SI Text.…”

Section: Methodsmentioning

confidence: 99%

“…To do this, we used a model that one of us (S.B.) had published previously which specifies the transmission dynamics of wild-type and resistant strains in the presence of therapeutic programs (16). This model had been parameterized using epidemiological, clinical, and behavioral data to reflect the HIV epidemic in the MSM The black line delimits the threshold at which a PrEP intervention would have no effect on increasing the number of resistant infections; below the line the number decreases, and above the line the number increases.…”

Section: Methodsmentioning

confidence: 99%

“…In the absence of PrEP interventions, the PrEP intervention model is similar in structure to the model described in ref. 16 …”

mentioning

confidence: 99%

See 3 more Smart Citations

HIV, transmitted drug resistance, and the paradox of preexposure prophylaxis

Supervie

Garcı́a-Lerma²,

Heneine³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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101

129

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The administration of antiretrovirals before HIV exposure to prevent infection (i.e., preexposure prophylaxis; PrEP) is under evaluation in clinical trials. Because PrEP is based on antiretrovirals, there is considerable concern that it could substantially increase transmitted resistance, particularly in resource-rich countries. Here we use a mathematical model to predict the effect of PrEP interventions on the HIV epidemic in the men-who-have-sex-with-men community in San Francisco. The model is calibrated using Monte Carlo filtering and analyzed by constructing nonlinear response hypersurfaces. We predict PrEP interventions could substantially reduce transmission but significantly increase the proportion of new infections caused by resistant strains. Two mechanisms can cause this increase. If risk compensation occurs, the proportion increases due to increasing transmission of resistant strains and decreasing transmission of wild-type strains. If risk behavior remains stable, the increase occurs because of reduced transmission of resistant strains coupled with an even greater reduction in transmission of wild-type strains. We define this as the paradox of PrEP (i.e., resistance appears to be increasing, but is actually decreasing). We determine this paradox is likely to occur if the efficacy of PrEP regimens against wild-type strains is greater than 30% and the relative efficacy against resistant strains is greater than 0.2 but less than the efficacy against wildtype. Our modeling shows, if risk behavior increases, that it is a valid concern that PrEP could significantly increase transmitted resistance. However, if risk behavior remains stable, we find the concern is unfounded and PrEP interventions are likely to decrease transmitted resistance.mathematical model | men who have sex with men | prevention | epidemics | antiretrovirals T he administration of antiretroviral drugs (ARVs) before HIV exposure to prevent infection (i.e., preexposure prophylaxis; PrEP) is currently under evaluation in clinical trials (1). The PrEP regimens under consideration are based on tenofovir (TDF) alone or in combination with emtricitabine (FTC). Results from phase III efficacy trials are expected in 2010 and several additional trials will begin soon (SI Appendix, Table S1) (2). The results from these trials are widely anticipated because, if PrEP is shown to be safe and effective, it will become an important biomedical intervention for controlling the HIV pandemic. A phase II study of TDF-based PrEP showed daily TDF in HIV-uninfected women to be safe (3). However, because PrEP is based on ARVs, there is concern that wide-scale usage could lead to a substantial increase in transmission of ARV-resistant strains (4). Such an increase would have significant clinical repercussions [as individuals infected with these strains would be limited in their future treatment options (5)], as well as exacerbate the difficulty of controlling the pandemic. In particular, increases in resistance in high-risk communities in resource-rich countries...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…In the absence of PrEP interventions, the PrEP intervention model is similar in structure to the model described in ref. 16 …”

mentioning

confidence: 99%

See 2 more Smart Citations

HIV, transmitted drug resistance, and the paradox of preexposure prophylaxis

Supervie

Garcı́a-Lerma²,

Heneine³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

101

129

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“…In the UARTO pilot study (Kampala/AMU), a total of 62% participants were female with a median age of 36 years (IQR [30][31][32][33][34][35][36][37][38][39][40], baseline log viral load of 5.5 (IQR 4.9-5.8), and baseline CD4 count of 60 (IQR 12-136). All AMU participants received generic fixed dose combinations of d4T/3TC/ NVP as a first regimen.…”

Section: Baseline Characteristicsmentioning

confidence: 99%

Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

Lee

Bangsberg

Muzoora

et al. 2014

AIDS Research and Human Retroviruses

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Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n = 81 and n = 491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002(AMU -2004 and main cohort in Mbarara (MBA 2005(MBA -2010. TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (£ 400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p = 0.2 and 0.1); time to suppression (log-rank p = 0.3 and p = 0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure.

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Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection

Ray

George

et al. 2011

Cochrane Database of Systematic Reviews

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Evolutionary Dynamics of Complex Networks of HIV Drug-Resistant Strains: The Case of San Francisco

Cited by 106 publications

References 29 publications

HIV, transmitted drug resistance, and the paradox of preexposure prophylaxis

HIV, transmitted drug resistance, and the paradox of preexposure prophylaxis

Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection

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