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Functional cure and seroreversion after advanced HIV disease following 7-years of antiretroviral treatment interruption
Abstract Content:
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.
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.