Good News, Bad News
The HIV cure front faces disappointment mixed with hope
by Jeannie Wraight
The past year has been a difficult one in the HIV cure arena. Several promising and widely reported cases of HIV clearance concluded with disappointing results, as the virus remerged despite high hopes and expectations to the contrary. Now two novel and interesting cases have been detailed sparking new hopes, questions, and concerns.
The Good News
An abstract, presented at the XX International AIDS Conference, described an Argentinean woman who seroreverted years after being diagnosed with advanced HIV disease. Cases (such as the Visconti cohort) have been previously reported of individuals who began antiretroviral therapy within several months of HIV infection, discontinued therapy and remain undetectable. However, this is the first case reported of a person who had progressed to AIDS and is reported “functionally cured” after discontinuation of ART.
This case puts forth an interesting question: Are there others who have seroreverted after being diagnosed with AIDS and being on therapy for years’?
According to Dr. Analia Uruena of Helios Salud, Buenos Aires, Argentina, and colleagues, the fifty-one-year-old woman was hospitalized in 1997 with wasting syndrome and toxoplasma encephalitis. At the time of hospitalization, the woman tested HIV-positive on two Western Blot tests. No baseline viral load measurement or CD4 counts are available.
The woman was treated for toxoplasma encephalitis and was provided AZT, ddI, and nevarapine, a standard-of-care HIV regimen at the time. She subsequently experienced treatment failure one year after initiating therapy.
She was then started on D4T, 3TC, and indinavir and achieved and maintained viral suppression. Three years later, indinavir was switched to abacavir, and she remained on this regimen until discontinuation of ARVs in 2007 due to dyslipidemia and lipodystrophy.
The woman has remained undetectable since beginning D4T, 3TC, and indinavir in November of 1997, with the exception of a single viral load blip at 54 copies, in August 2000. Subsequent tests have found no remaining HIV antibodies and no HIV provirus in PBMCs (peripheral blood mononucleated cells). Her CD4 counts range from 568 to 895 and she has a current CD4/CD8 ratio of 1.4. She is reported to be absent of the delta 32 deletion and the protective HLA-B alleles.
The Bad News
Last spring the news of the reemergence of virus in the “Mississippi Baby” dashed hopes that “curing” newborns of HIV was in reach. Doctors had hoped that immediate and aggressive antiretroviral therapy in newborns might be able to clear HIV before viral reservoirs had a chance to form. A case reported in the October issue of the Lancet adds further doubt that this may be possible.
The case of an Italian baby boy who received duel HIV therapy hours following birth, presented some interesting and concerning questions in regards to immediate ART in newborns. Sensitive assays had shown that the child temporarily cleared HIV, only for the virus to reemerge three years later, shortly after the discontinuation of antiretroviral therapy. What sets this case apart from the “Mississippi Baby” is that during the time that HIV appeared to vanish, signs of immune activation, often seen in HIV patients, continued to occur.
In December of 2009 a woman with a history of intravenous drug use who was unaware of her HIV status, received care at a hospital in Milan. At forty-one weeks of pregnancy, she gave birth to a small, premature baby boy.
At twelve hours-old, the infant tested HIV-positive with the Western Blot and HIV-1 antigen P24 assays. He had a viral load of 152,560 copies per mL. He immediately received zidovudine and nevirapine as prophylaxis and, by Day 3, his viral load had dropped to 13,530. He was then given ritonavir-boosted lopinavir, zidovudine, and lamivudine and experienced viral load decreases to 3,971 copies per mL by Day 15, 49 copies after three months, and below the level of detection at six months.
ARVs were discontinued at three years of age after the child tested negative for HIV antibodies, DNA, p24, and RNA. Despite finding no trace of HIV, upon examination of PBMCs, doctors found activated CD4 and CD8 T cells, alterations of the T-cell differentiation pathway, with reduced naive and central memory, increased effector memory and terminally differentiated CD4 and CD8 T cells, all consistent with HIV infection.
After two weeks off of treatment, the child’s viral load rebounded to 36,840 copies per mL and treatment was reinitiated. Ten days later tests for HIV antibodies and antigens were once again positive. After three months back on treatment, the child’s viral load was undetectable.
This case was different from the “Mississippi Baby” in that, despite testing HIV-negative after ARVs, immune responses similar to those seen in HIV-positive people occurred. This could be an indication of ongoing HIV replication. The authors hypothesize that the low birth weight of the child, early in utero infection and high baseline viral load may have hindered ongoing viral remission.
Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody. com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in the Bronx, New York.