Functional cure and seroreversion after advanced HIV disease following 7-years of antiretroviral treatment interruption
Background: Very early antiretroviral treatment (ART) during
primary infection can lead to functional cure in a subset of patients called post-treatment
controllers. However, there is no evidence that functional cure can be reached
after chronic HIV-1 infection. We report a 51-year old female diagnosed with
advanced HIV-1 infection that has no detectable HIV-1 viremia and seroreverted
after 7 years off-ART.
Methods: Case report of a patient hospitalized in 1996 with
wasting syndrome and probable toxoplasma encephalitis. Two HIV-1 positive ELISA
tests and a positive Western Blot (WB) confirmed HIV-1 infection. She was
treated with pyrimetamin and clindamicin and started on zidovudine, didanosine
and nevirapine soon after diagnosis. Pre-treatment HIV-1 viral load (VL) and
CD4+ T cell count are not available.
After two weeks on ART, her CD4+ T cell count and VL were 164 cells/µl
and 2,200 RNA copies/mL (RT-PCR), respectively. She recovered without
neurologic sequel. She developed virological failure after one year with VL 36,000
copies/mL (Nasba HIV-1) and CD4+ T cell count 490 (32%) cells/µl. ART was changed
to stavudine, lamivudine and indinavir in Nov 1997 and, thereafter, VL
persisted < 50 RNA copies/mL. ART was
interrupted in 2007 due to dyslipidemia and lipodystrophy. She remains undetectable
with successive VLs less than 400, 50 or 20 copies/mL depending on the
available test (Roche® Standard or Ultrasensitive RT-PCR Amplicor -automated
Cobas-, and Cobas/Ampliprep, respectively).
Results: CD4+ T cell count remained stable between 568-885
cells/µl since 2007. Current CD4/CD8 ratio is 1.4 and VL by Cobas/Ampliprep and
bDNA CHIRON HIV-1 RNA 3.0 was < 20 and < 50 RNA copies/mL, respectively. Proviral
HIV-DNA was not detected in PBMCs by PCR targeting gag, pol and env genes. No CCR5 delta 32 deletion was
detected. HLA-B (Luminex) was 41;58. HIV-1 ELISA and WB were re-tested,
resulting no reactive in two separate samples.
Conclusions: This is the first report of a functional
cure case that also seroreverted after advanced HIV disease and suggests that post-treatment
control could be achieved following chronic HIV-1 infection. Further studies
are undergoing to assess HIV-1 reservoirs in this patient.
A. Urueña1, A. Mangano2, R. Arduino3, P. Aulicino2, I. Cassetti1
1Helios Salud, Ciudad Autónoma de Buenos Aires, Argentina, 2Hospital de Pediatría 'Prof. Dr. J.P. Garrahan', Laboratorio de Biología Celular y Retrovirus-CONICET, Ciudad Autónoma de Buenos Aires, Argentina, 3The University of Texas Health Science Center, Houston, United States