Clinical Utility of HIV Standard Genotyping among Antiretroviral-Naive Individuals with Unknown Duration of Infection

Smith, Davey M.; Moini, Niousha; Pesano, Rick L.; Cachay, Edward R.; Aiem, Heidi; Lie, Yolanda; Richman, Douglas D.; Little, Susan J.

doi:10.1086/510748

Cited by 41 publications

(39 citation statements)

References 15 publications

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“…Macaques that failed PrEP were first infected with wild-type virus and only developed resistance after a few weeks (17). This is similar to how resistance is selected when an individual is receiving treatment (28). Rapid reversions of acquired TDF and FTC mutations have been observed in humans after stopping therapeutic treatment (29)(30)(31).…”

Section: (Materials and Methods)mentioning

confidence: 90%

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

Supervie

Garcı́a-Lerma²,

Heneine³

et al. 2010

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

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: (Materials and Methods)mentioning

confidence: 90%

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

Supervie

Garcı́a-Lerma²,

Heneine³

et al. 2010

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

101

129

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“…Susceptibility to antiretroviral (ARV) drugs is a critical component of HIV-1 treatment success and survival [1][2][3]. In Europe and North America, the estimated prevalence of primary ARV drug-resistant (ARV-DR) HIV infection is 5-26.7% in the ARV era, prompting international recommendations for baseline ARV-DR testing prior to initiation of therapy [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Antiretroviral drug resistance among antiretroviral‐naïve persons with recent HIV infection in Thailand

Thatrimontrichai

Jirayasethpong²,

Sa-nguansilp

et al. 2008

HIV Medicine

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ObjectivesTo evaluate the prevalence and patterns of antiretroviral (ARV) drug resistance (ARV-DR) among ARV drug-naïve, recently infected persons with HIV in the 4-year interval (2003)(2004)(2005)(2006) after the inception of the National Access to ARV Programme for People who have AIDS in Thailand. MethodsCross-sectional study of patients with recent HIV infection for HIV risks, ARV-DR risks and baseline ARV-DR. ResultsSeven of the 305 patients (2%) had baseline ARV-DR. Via contract tracing, all seven patients with transmitted ARV-DR identified sexual partners with prior ARV treatment failure and had documented low (o75%) ARV adherence. Annual ARV-DR increased from 0 to 5.2% (P 5 0.06) between 2003 and 2006. ConclusionsReport of sexual partners with potential HIV and ARV drug exposures can prompt baseline ARV-DR testing of at-risk individuals, while behavioural interventions for adherence and safer sex are refined to minimize the emergence of resistance to generic, fixed-dose combination stavudine, lamivudine and nevirapine (GPO-VIR) therapy.

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“…Not knowing the duration of infection in our cohort could be a methodological limitation because any reversion of a drug-resistance mutation to wild-type would cause an underestimation of the prevalence of TDR, and this may occur more frequently in other drug classes [12,37]. However, not knowing the exact duration of HIV infection is often the case in most clinical scenarios, and without knowing the duration of infection in our cohort, we still found a rate of HIV TDR comparable to that seen with primary HIV infection [9,10,13], which is entirely consistent with the long duration of TDR, particularly with NNRTI [12,37].…”

Section: Discussionmentioning

confidence: 99%

“…In the United States, reported rates of TDR to at least one class of ARV medications ranges from 8 to 24% [9][10][11][12][13]. In California, the majority of HIV TDR results in decreased susceptibility to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of ARV medications [12,14].…”

Section: Introductionmentioning

confidence: 99%

“…*Address correspondence to this author at the University of California, San Diego Medical Center, 200 West Arbor Drive, San Diego, CA 92103-8681, USA; Tel: (619) 543-3939; Fax: (619) 543-7841; E-mail: ecachay@ucsd.edu Among MSM, there is a confluence of high prevalence of HIV infection, TDR and methamphetamine use [12,15]. Indeed, frequent methamphetamine use among recently HIV infected MSM is associated with TDR to NNRTI [16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Active Methamphetamine Use is Associated with Transmitted Drug Resistance to Non-Nucleoside Reverse Transcriptase Inhibitors in Individuals with HIV Infection of Unknown Duration

Moini¹,

Pond²,

Pesano³

et al. 2007

TOAIDJ

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Abstract:Background: Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration.Design: Cross-sectional analysis.Methods: Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq™, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models.Results: Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Conclusion:Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI.

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Clinical Utility of HIV Standard Genotyping among Antiretroviral-Naive Individuals with Unknown Duration of Infection

Cited by 41 publications

References 15 publications

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

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

Antiretroviral drug resistance among antiretroviral‐naïve persons with recent HIV infection in Thailand

Active Methamphetamine Use is Associated with Transmitted Drug Resistance to Non-Nucleoside Reverse Transcriptase Inhibitors in Individuals with HIV Infection of Unknown Duration

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