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No HIV RNA or DNA, Negative Western Blot, After 7-Year ART Suspension
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20th International AIDS Conference, July 20-25, 2014, Melbourne
Mark Mascolini
An Argentine woman who started antiretroviral therapy (ART) with advanced chronic infection, reached an undetectable viral load, then suspended treatment for 7 years has no detectable HIV RNA or proviral HIV DNA and tests negative for HIV antibodies [1]. The woman does not have HLA gene patterns or the CCR5 delta32 deletion linked to protection from HIV.
Functional cure--lack of HIV replication without ART--has been described after ART suspension, notably in the French VISCONTI study [2]. But the case from Argentina appears to be the first report of functional cure and negative antibody tests (seroreversion) after interruption of ART begun in advanced chronic infection. The case is all the more intriguing because the woman involved appears to carry no genetic traits known to confer protection against HIV infection or progression. Indeed, the literature is rife with reports of virologic rebound after treatment interruption, even after people test negative for proviral DNA and HIV antibody off treatment.
Researchers from Ciudad Autonoma of Buenos Aires and colleagues described the case of a 51-year-old woman admitted to the hospital in 1996 with AIDS wasting and probable toxoplasma encephalitis. Positive ELISA and western blot tests confirmed HIV infection. She began pryrimethamine, clindamycin, and leucovorin for encephalitis and three antiretrovirals--nevirapine, zidovudine, and didanosine. The investigators have no record of pretreatment viral load or CD4 count. Two weeks after treatment began, this woman had a viral load of 2200 copies and a CD4 count of 164.
The woman recovered from encephalitis but the antiretroviral regimen failed after 1 year when her viral load rebounded to 36,000 copies. In November 1997, with a CD4 count of 490 and a CD4 percent of 32%, she began indinavir plus stavudine and lamivudine. Her viral load became undetectable and remained so, except for one blip to 54 copies in August 2000. In November 2000 she replaced indinavir with abacavir, and in 2007 she stopped her antiretrovirals entirely because of lipodystrophy and abnormal lipids. But her viral load has remained undetectable ever since 2007.
The woman's CD4 count stayed between 568 and 885 since she stopped ART, and her CD4/CD8 ratio now stands at 1.4, in the normal range. Her viral load has remained below the detection limit of standard and ultrasensitive (RT-PCR Amplicor) assays since she stopped treatment. HIV DNA cannot be detected in peripheral blood mononuclear cells by real-time PCR targeting the pol gene and nested PCR targeting gag, pol, and env. Antibodies against HIV-1 and HIV-2 cannot be detected by quimioluminiscence or HIV-1 western blot. PCR confirms absence of the CCR5 delta32 deletion linked to protection against HIV, and HLA gene assessment shows no known protective variations.
The Buenos Aires team classifies this case as a functional cure with seroreversion. They plan further assessment of viral reservoirs in T cells and immunologic response to HIV-1.
References
1. Uruena A, Mangano A, Arduino R, Aulicino P, Cassetti I. Functional cure and seroreversion after advanced HIV disease following 7-years of antiretroviral treatment interruption. AIDS 2014. 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract MOPE016.
2. Saez-Cirion A, Bacchus C, Hocqueloux L, et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI study. PLoS Pathog. 2013;9:e1003211.
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