Prevalence and Predictive Value of Intermittent Viremia With Combination HIV Therapy

Havlir, Diane V.; Bassett, Roland L.; Levitan, Diane; Gilbert, Peter B.; Tebas, Pablo; Collier, Ann C.; Hirsch, Martin S.; Ignacio, Caroline; Condra, Jon H.; Günthard, Huldrych F.; Richman, Douglas D.; Wong, Joseph K.

doi:10.1001/jama.286.2.171

Cited by 328 publications

(292 citation statements)

References 39 publications

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“…The assay-detection threshold of 500 copies/mL was commonly used when many of our participants started HAART, but it has recently decreased to 50 copies/mL. 33,34 In summary, we found that among HIV-infected injection drug users who were on antiretroviral therapy, any alcohol use and incarceration in the 6 months prior to initiating antiretroviral therapy were negatively associated with achieving HIV-1 RNA suppression. High level of adherence in the first year of therapy, longer time on therapy, lower baseline HIV-1 RNA level, and the use of HAART were also independently associated with superior virologic outcome.…”

Section: Discussionmentioning

confidence: 69%

Alcohol Use and Incarceration Adversely Affect HIV-1 RNA Suppression Among Injection Drug Users Starting Antiretroviral Therapy

Palepu

Tyndall

et al. 2003

Journal of Urban Health: Bulletin of the New York Academy of Me

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Section: Discussionmentioning

confidence: 69%

Alcohol Use and Incarceration Adversely Affect HIV-1 RNA Suppression Among Injection Drug Users Starting Antiretroviral Therapy

Palepu

Tyndall

et al. 2003

Journal of Urban Health: Bulletin of the New York Academy of Me

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“…Prolonged breaks in adherence may thus represent islands of infectivity where host infectiousness relates positively to pretreatment SPVL. Finally, viral “blips” (brief and intermittent periods of detectable viral load despite adherence to ART) are observed more often in hosts with high baseline SPVL (Havlir et al., 2001; Leierer et al., 2015), and infections with large or frequent blips are more likely to experience virologic failure (Easterbrook et al., 2002; Grennan et al., 2012; Laprise, De Pokomandy, Baril, Dufresne, & Trottier, 2013) and achieve higher viral rebound upon treatment interruption (Castro et al., 2013). These observations span drug types, host populations and viral clades, but collectively support the intuitive assumption that infections with high SPVL are more infectious than those with low SPVL when imperfectly treated.…”

Section: Discussionmentioning

confidence: 99%

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Mideo

2017

Evolutionary Applications

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Average HIV‐1 virulence appears to have evolved in different directions in different host populations since antiretroviral therapy first became available, and models predict that HIV drugs can select for either higher or lower virulence, depending on how treatment is administered. However, HIV virulence evolution in response to “leaky” therapy (treatment that imperfectly suppresses viral replication) and the use of preventive drugs (pre‐exposure prophylaxis) has not been explored. Using adaptive dynamics, we show that higher virulence can evolve when antiretroviral therapy is imperfectly effective and that this evolution erodes some of the long‐term clinical and epidemiological benefits of HIV treatment. The introduction of pre‐exposure prophylaxis greatly reduces infection prevalence, but can further amplify virulence evolution when it, too, is leaky. Increasing the uptake rate of these imperfect interventions increases selection for higher virulence and can lead to counterintuitive increases in infection prevalence in some scenarios. Although populations almost always fare better with access to interventions than without, untreated individuals could experience particularly poor clinical outcomes when virulence evolves. These findings predict that antiretroviral drugs may have underappreciated evolutionary consequences, but that maximizing drug efficacy can prevent this evolutionary response. We suggest that HIV virulence evolution should be closely monitored as access to interventions continues to improve.

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“…Other reports have described successful modifications of the Abbot Real Time assay and the Amplicor Ultrasensitive assays, including an ultra-centrifugation step and increased sample volumes [19,21], but did not evaluate amplification of different subtypes. To our knowledge this is the first report of an ultrasensitive detection of various subtypes by a modified commercial HIV-1 RNA assay.…”

Section: Discussionmentioning

confidence: 99%

“…Eleven patients were infected with HIV-1 subtype B. Four patients crease their sensitivity [19][20][21]. For example, Havlir, et al increased the sensitivity by using ultra-centrifugation prior to amplification with the Roche Amplicor Ultrasensitive assay [19].…”

Section: Clinical Specimensmentioning

confidence: 99%

“…Four patients crease their sensitivity [19][20][21]. For example, Havlir, et al increased the sensitivity by using ultra-centrifugation prior to amplification with the Roche Amplicor Ultrasensitive assay [19]. Another, more recent study showed a single-copy sensitivity by increasing the sample volume, and adding an ultra-centrifugation step to the Abbott Real Time assay [21].…”

Section: Clinical Specimensmentioning

confidence: 99%

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Sensitive, Subtype Independent HIV-1 PCR Assays for Assessment of Residual Viremia and Total HIV-1 DNA

Mellberg¹

2017

Int J Virol AIDS

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Background: Correct measurements of residual viremia and reservoir size are crucial in HIV-1 eradication trials and there is a need for sensitive and automated assays. The increasing worldwide diversity of HIV-1 subtypes stresses the importance of subtype independent assays. Methods:We added an ultra-centrifugation step to the COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0 and evaluated assay sensitivity. A previously published method for quantification of total HIV-1 DNA was also evaluated. Nineteen clinical samples from virologically suppressed cART treated patients infected with various HIV-1 subtypes were analysed. The relationship between plasma HIV-1 RNA and HIV-1 DNA in Peripheral Blood Mononuclear Cells (PBMC) was studied. Results:The HIV-1 RNA PCR assay reached a limit of quantification of 3 copies/ml of plasma. The total HIV-1 DNA assay allowed quantification to 3 copies/million cells with an intra-and inter-assay coefficient of variation of 13.2% and 23.2% respectively. All subtypes studied were quantified by the HIV-1 RNA PCR assay and the HIV-1 DNA assay quantified all subtypes except CRF_AE. No significant correlation was observed between plasma HIV-1 RNA and total HIV-1 DNA in PBMC.Conclusions: By modification of a commercial assay, we achieved a sensitive quantification of plasma HIV-1 RNA that could be used to assess residual viremia. Sensitive quantification of total HIV-1 DNA in PBMC was also demonstrated. The assays were subtype independent to a large extent, making them useful for research and clinical use in settings where a variety of HIV-1 subtypes is present.

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Prevalence and Predictive Value of Intermittent Viremia With Combination HIV Therapy

Cited by 328 publications

References 39 publications

Alcohol Use and Incarceration Adversely Affect HIV-1 RNA Suppression Among Injection Drug Users Starting Antiretroviral Therapy

Alcohol Use and Incarceration Adversely Affect HIV-1 RNA Suppression Among Injection Drug Users Starting Antiretroviral Therapy

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Sensitive, Subtype Independent HIV-1 PCR Assays for Assessment of Residual Viremia and Total HIV-1 DNA

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