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Three in 30 Infants Treated in First 48 Hours of Life Become PCR Negative
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Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle
Mark Mascolini
Three of 30 South African infants (10%) starting antiretroviral therapy (ART) within the first 48 hours of life attained PCR-negative status, meaning HIV could no longer be detected in their blood by standard polymerase chain reaction (PCR) [1]. Ten other infants reached and maintained an undetectable viral load, but the remaining infants did not achieve or maintain undetectability or died.
The closely studied "Mississippi baby" started ART in the first 30 hours of life and maintained viral suppression for 27 months when treatment inadvertently stopped [2]. This case and others spawned intense interest in immediate ART for PCR-positive neonates in hopes of limiting viral reservoirs and perhaps inducing sustained viral remission without ART. A recent study of two South African infant cohorts found that starting ART within the first 6 months of life sustained viral suppression better than starting ART later [3]. But analysis of another three infant cohorts by the same investigators [3] found that starting ART within 6 month did not raise chances of initial viral suppression.
Although HIV infection can be identified soon after birth, there have been few reports of infants treated in the first days of life. Collaborators at the University of Witwatersrand in Johannesburg and Columbia University in New York gathered the new findings on 30 South African neonates treated within the first 48 hours of life.
All infants started treatment with nevirapine plus zidovudine/lamivudine. Six began within 24 hours of birth. They replaced nevirapine with lopinavir/ritonavir at a median age of 27 days. The study group consisted of 17 boys and 13 girls; birth weight averaged 3015 g (6.6 pounds). Pre-ART viral load stood below 400 copies in 1 infant, at 400-1000 copies in 2, at 1000-5000 copies in 4, at 5000-20,000 in 8, at 20,000-50,000 in 5, and higher in the remaining infants.
Three infants (10%), all boys, died at ages 43, 61, and 89 days. Their birth weights were 2405 g, 2950 g, and 3710 g (5.3 to 8.2 pounds). All had transitioned to lopinavir/ritonavir before dying.
The research team measured HIV RNA in plasma before ART and at weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 with an assay that has a lower detection limit of 20 copies. Eight infants (27%) never reached an undetectable viral load. Six infants (20%) reached an undetectable load and rebounded. Three infants (10%) reached and maintained an undetectable load. Seven infants (23%) had a target-not-detectable reading on their PCR. And 3 infants (10%) reverted to PCR-negative status. These 3 infants became PCR negative around days 150, 165, and 180, all after switching to lopinavir/ritonavir.
The Witwatersrand-Columbia team concludes that virologic response is variable in infants who begin ART in the first 48 hours of life. But more than one third reach and maintain an undetectable viral load. And a "nonnegligible" proportion reverts to PCR-negative status.
References
1. Kuhn L, Technau K, Strehlau R, et al. Treatment of acute HIV infection in neonates. Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle. Abstract 27.
2. Persaud D, Gay H, Ziemniak C, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013;369:1828-1835.
http://www.nejm.org/doi/full/10.1056/NEJMoa1302976
3. Shiau S, Strehlau R, Technau KG, et al. Early age at start of antiretroviral therapy associated with better virologic control after initial suppression in HIV-infected infants. AIDS. 2017;31:355-364.
http://journals.lww.com/aidsonline/Abstract/2017/01280/Early_age_at_start_of_antiretroviral_therapy.7.aspx
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