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Recent evidence suggests that treatment very early in acute HIV infection limits seeding of viral reservoirs and — in some instances — might enable virologic control, even after discontinuation of antiretroviral therapy (ART). However, the effects of very early treatment after in utero or perinatal HIV acquisition are not well understood.
Researchers now describe the clinical course and laboratory findings of the “Mississippi child,” who — because of high-risk exposure — was started on combination ART 30 hours after birth. Testing during labor had revealed HIV infection in the mother; delivery had occurred before administration of antiretroviral prophylaxis. The mother had a relatively low viral load (2423 copies/mL).
At approximately 30 hours after birth, the child had detectable HIV DNA in peripheral blood mononuclear cells and a viral load of 19,812 copies/mL. After ART initiation, the viral load declined, as typically occurs with effective treatment of established infection; 28 days later, it was below the level of detection by commercial assay. ART was discontinued at age 18 months, according to the mother, and commercial viral load and antibody testing remained negative 12 months thereafter.
Sensitive testing was conducted to evaluate the persistence of HIV infection. Low-level, residual viremia was detected in plasma at 24 months of age but not at 26 months; co-culture assays of CD4 cells at 24 months did not yield replication-competent virus. However, low levels of HIV DNA were quantified just at the detection threshold of a sensitive assay at 24 and 26 months. Interestingly, no HIV DNA was found in resting CD4 cells, the best-described long-term HIV reservoir.
Persaud D et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med 2013 Oct 23; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1302976)
Comment
The Mississippi child is different from adults who experience antiretroviral therapy–free virologic control after very early treatment initiation, because only traces of viral genetic material remained after treatment interruption. Nonetheless, this provocative study adds to the growing body of literature suggesting that early ART may be beneficial in limiting the seeding of viral reservoirs. It is possible that restricting reservoir seeding could lead to virologic control after ART cessation in certain individuals, but the durability of remission in this child remains to be determined. All eyes are eagerly watching.