therapy started soon after birth can suppress HIV to extremely low levels and
severely restrict the size of the reservoir of HIV-infected cells in peripheral
blood, Canadian researchers report in the online edition of Clinical Infectious Diseases.
The findings raise
the hope that early suppressive antiretroviral therapy can achieve a "functional cure" for HIV-infected babies. However, the authors caution that
the only way to determine this would be to discontinue HIV treatment, a
strategy that is not without risks.
baby who started antiretroviral therapy within 30 hours of birth was recently
reported to have no detectable virus after treatment was stopped. The case of
the so-called “Mississippi Baby” raised the prospect of a “functional cure” for
HIV – control of viral replication after withdrawal of antiretroviral
Doctors from three
hospitals in Canada therefore investigated the impact of early antiretroviral
treatment on HIV replication and various measures of the HIV reservoir size in
children infected with HIV at birth who achieved sustained virologic
suppression with triple antiretroviral therapy.
infants were eligible for inclusion if they started treatment within 72 hours of
life because of incomplete maternal HIV suppression at delivery, the absence of
viral load results, or a history of poor adherence.
infants all had confirmed HIV infection and achieved sustained HIV suppression
with antiretroviral therapy consisting of zidovudine, lamivudine and
undertaken after 2.5-7.5 years. Assessments included HIV antibody testing, viral
load testing with a lower limit of detection of 1.5 copies/ml, monitoring of
cell-associated HIV DNA and RNA, tests for the presence of
replication-competent HIV and HLA genotype.
A total of 136
infants started combination antiretroviral therapy soon after birth; twelve (9%)
were HIV infected. Of these twelve, four achieved sustained viral suppression, whereas eight had difficulties with adherence. Analysis
focused on the four patients with sustained viral suppression. All received their first dose of therapy within
24 hours of birth. Virological suppression was first documented between 66 and
189 days of life. All four infants remained on the same regimen until follow-up
and at this time were in good health with normal CD4 counts.
At follow-up, all
four infants were HIV-negative using both ELISA and Western blot tests. Viral
load was undetectable using the ultra-sensitive assay. No detectable cell-associated HIV DNA
(below 2.6 copies/106 CD4 T-cells) was found in the peripheral blood
of any of the children. However, low levels of cell-associated HIV RNA
(19.5-130 copies/1.5 μg RNA) were
detected in all four. No virion-associated HIV RNA was detected in the patients’
CD4 cells. Culture detected replication-competent virus in one child at a
concentration of 0.1 infectious units per 106 CD4 cells.
All four children
had wild-type CCR5 virus. Three had HLA B*58. The HLA-B sequence has previously
been associated with better HIV control.
“The findings in
the four children with sustained virologic suppression show that early
initiation of cART [combination antiretroviral therapy] in infants can
dramatically reduce the level of proviral HIV-1 DNA and replication competent
virus in peripheral blood CD4+ T-cells,” comment the authors. “Given
that it is not possible to examine every cell in each infant, a structured
treatment interruption may be the only practical way to determine if HIV-1
eradication or functional cure can be achieved in such treatment.”
urge that the pros and cons of this strategy should be carefully assessed.
rebound were to occur following cART discontinuation it would likely be
accompanied by expansion of the HIV-1 reservoir, potentially making future
HIV-1 reservoir eradication more difficult,” they conclude. “Therefore, a
thorough discussion of the risks and benefits of stopping cART with patients
and caregivers is imperative and, if undertaken, will require long-term