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HIV-1 DNA predicts disease progression and post-treatment virological control.

ABSTRACT: In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.

SUBMITTER: Williams JP

PROVIDER: S-EPMC4199415 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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HIV-1 DNA predicts disease progression and post-treatment virological control.

Williams James P JP Hurst Jacob J Stöhr Wolfgang W Robinson Nicola N Brown Helen H Fisher Martin M Kinloch Sabine S Cooper David D Schechter Mauro M Tambussi Giuseppe G Fidler Sarah S Carrington Mary M Babiker Abdel A Weber Jonathan J Koelsch Kersten K KK Kelleher Anthony D AD Phillips Rodney E RE Frater John J

eLife 20140912

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of indi ...[more]

PMID: 25217531

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Project description:INTRODUCTION:Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated. METHODS:We modeled HIV disease progression as a function of changes in viral load and CD4 count over time among ART naïve persons. The disease progression Markov model was nested within a dynamic model of HIV transmission at population level. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/?L, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to retention in HIV care. We estimated the potential impact of valacyclovir on onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. RESULTS:The average duration of HIV infection was 9.5 years. The duration of disease before reaching CD4 200cells/?L was 2.53 years longer for females than males. Relative to a baseline of ART initiation at CD4?500cells/?L, the valacyclovir scenario resulted in 167,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $5276 per HIV infection averted. A Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 350,000 fewer HIV infections at an ICER of $2822 and $812 per HIV infection averted and QALY gained, respectively. CONCLUSION:Even when compared with valacyclovir suppression, a drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment would most effectively and efficiently reduce the HIV burden.

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HIV-1 DNA predicts disease progression and post-treatment virological control.

Publications

HIV-1 DNA predicts disease progression and post-treatment virological control.

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