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In neonates with acquired in utero HIV infection, administration of antiretroviral therapy (ART) within 48 hours of life can lead to sustained HIV virological suppression by 2 years, a phase I/II proof-of-concept study indicated.

In two cohorts who received three-drug nevirapine-based ART regimens within two days of life and maintained protocol- defined virological control criteria to week 108 of the study, 64% of infants in cohort 1 and 71% of infants in cohort 2 had no detected HIV-1 DNA, reported Deborah Persaud, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The estimated probability of maintaining undetectable plasma RNA to 2 years was 33% for cohort 1 and 57% for cohort 2, they noted in the .

At week 108, 83% of infants in cohort 1 and 100% of infants in cohort 2 tested negative for HIV-1, and among the 54 infants initiated on very early ART, 19% met criteria for possible treatment interruption.

"We set out to test whether treating newborns who acquired HIV in utero very early -- within 48 hours of life -- would lead to sustained virologic suppression on neonatal ART and to a marked decrease in the amount of HIV-infected cells lingering on ART," Persaud told MedPage Today in an email.

"At 2 years of age, 10 of them, nearly 20% of the 54 infants, had both HIV DNA and HIV antibodies not detected in the blood -- making them eligible to consider stopping the study ART regimen to see if they have experienced ART-free remission, in which the virus doesn't return within the usual 2 to 4 weeks of stopping ART," she said. "This allows us to test the therapeutic concept of very early antiretroviral treatment of neonates to achieve ART-free remission, as we reported a decade ago on the case of a baby in Mississippi."

was infected with HIV in utero but received ART at 30 hours of age until 18 months, when treatment was withdrawn, Persaud explained. The infant achieved ART-free remission for 27 months, suggesting that early ART initiation could limit HIV viral reservoirs and even achieve a potential cure.

"The obvious clinical benefits in terms of morbidity and mortality of super early initiation of ART can no longer be ignored," wrote Philippe Van de Perre, MD, PhD, of the University of Montpelier in France, and Penny Moore, PhD, of the University of the Witwatersrand in Johannesburg, in an . "Guidelines for pediatric HIV care should urgently include super early diagnosis of neonates infected with HIV in utero and prompt initiation of ART during the window when mother-neonate pairs are still in the maternity ward. Implementation of such policies has the potential to spare some of these children from life-long ART therapy."

Persaud pointed out that it is critical to test pregnant people for HIV to not only prevent infection, but also to detect in utero HIV infection, so therapy can be initiated within the first few days of an infant's life.

"The goal of treatment remains the same, and that is to get to undetectable viral loads, stay undetectable, and keep children on their treatment regimen until we know how to get to ART-free remission, in which therapy can be stopped," she said.

"We are far from that goal, but these proof-of-concept clinical trials help us understand how to curtail these reservoirs and keep them at very low levels to help get to ART-free remission. ART is lifesaving for children, but we need better therapies to help with the challenge of adherence and long-term toxicities," she added.

The trial is an ongoing study enrolling infants with HIV acquired in utero at 30 research clinics in 11 countries, primarily in sub-Saharan Africa, but also other countries such as Brazil, Thailand, and the U.S. From January 2015 to December 2017, 34 infants were enrolled in cohort 1 (mean age at study entry 24.4 hours, 68% girls) and 20 were enrolled in cohort 2 (mean age at study entry 7.2 days, 50% girls).

Infants in cohort 1, whose mothers had HIV but were not receiving ART during pregnancy, received a three-drug oral ART regimen -- zidovudine or abacavir, lamivudine, and nevirapine. Infants in cohort 2, whose mothers had HIV and were receiving ART during pregnancy, were started on the same three-drug regimen, but with a lower dose of nevirapine that is normally used for prophylaxis. They then were switched to the same study regimen as the first group by 10 days of age.

To determine whether infants qualified for ART treatment interruption, the researchers assessed a predetermined biomarker profile at age 2 years that included undetectable RNA since week 48, HIV-1 antibody-negative, HIV-1 DNA not detected, and normal CD4 count and CD4 percentage.

Grade 3 or 4 adverse events occurred in 15 of the 34 infants in cohort 1 and seven of the 20 infants in cohort 2, most commonly reversible hematological toxicity due to zidovudine.

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