Early antiretroviral treatment of infants to attain HIV remission

Abstract

Background: Studies in adults and children suggested that starting antiretroviral therapy (ART) soon after infection positively influences early events in HIV infection raising the possibility that remission may be achieved in some.

Methods: We designed an analytic treatment interruption (ATI) trial to test the hypothesis that a sizable minority of HIV-infected neonates who initiated ART <14 days of birth and maintained on ART would be able to maintain viral suppression when ART was withdrawn. To yield the target cohort for this trial, 73 HIV-infected neonates identified at one hospital in Johannesburg, South Africa, were initiated on ART <14 days of birth and maintained on ART tracking viral load (VL) decline and immune recovery (clinicaltrials.gov # NCT02431975).

Findings: Three HIV-infected infants (4.1%) died and nine (12.3%) were lost to follow-up before 48 weeks of age. Of those surviving on study, 52.5% attained and sustained VL <50 copies/ml and half of these sustained CD4+ T-cell percentage >30% which were the primary entry criteria for the ATI trial. Proportions achieving ATI eligibility criteria were similar in the 46 infants starting ART <48 h (19.6%) to 27 infants starting 2-14 days (25.9%) (p = 0.567).

Interpretation: Very early ART on its own, using regimens available when the trial was designed, is insufficient to attain minimum entry criteria needed to justify our trial of ART interruption. Decisions about how quickly to start ART should be based on optimizing standard clinical outcomes rather than with the expectation that remission can be attained.

Funding: NICHD/NIAID (U01HD080441), South African Research Chairs Initiative of DST and NRF (South Africa).

Keywords: Antiretroviral therapy; HIV; Neonate; Remission.

Fig. 1

Flow diagram of screening to identify potential participants, their disposition prior to enrollment and follow-up after enrollment.

Fig. 2

Viral load and other characteristics of the three study participants who died on study. P indicates the timing of positive diagnostic PCR tests.

Fig. 3

Individual plots of viral load and CD4+ T-cell response to antiretroviral therapy of ten children in the study. P indicates the timing of positive, I indeterminate and N negative diagnostic PCR tests. A: Children who achieved and sustained target not detected and sustained CD4% >30% (3/61) B: Children who achieved and sustained target not detected but did not sustain CD4% >30% (7/61) C: Children who achieved and sustained <50 copies/ml and sustained CD4% >30% (13/61) D: Children who achieved and sustained <50 copies/ml but did not sustain CD4% >30% (9/61) E: Children who achieved <50 copies/ml but did not sustain this level (rebounded) and sustained CD4% >30% (6/61) F: Children who achieved <50 copies/ml but did not sustain this level (rebounded) and did not sustain CD4% >30% (8/61) G: Children who achieved and sustained <400 copies/ml but did not reach <50 copies/ml and sustained CD4% >30% (1/61) H: Children who achieved and sustained <400 copies/ml but did not reach <50 copies/ml but did not sustain CD4% >30% (1/61) I: Children who did not achieve <400 copies/ml (failure) but sustained CD4% >30% (3/61) J: Children who did not achieve <400 copies/ml (failure) and did not sustain CD4% >30% (10/61).

Fig. 3

Individual plots of viral load and CD4+ T-cell response to antiretroviral therapy of ten children in the study. P indicates the timing of positive, I indeterminate and N negative diagnostic PCR tests. A: Children who achieved and sustained target not detected and sustained CD4% >30% (3/61) B: Children who achieved and sustained target not detected but did not sustain CD4% >30% (7/61) C: Children who achieved and sustained <50 copies/ml and sustained CD4% >30% (13/61) D: Children who achieved and sustained <50 copies/ml but did not sustain CD4% >30% (9/61) E: Children who achieved <50 copies/ml but did not sustain this level (rebounded) and sustained CD4% >30% (6/61) F: Children who achieved <50 copies/ml but did not sustain this level (rebounded) and did not sustain CD4% >30% (8/61) G: Children who achieved and sustained <400 copies/ml but did not reach <50 copies/ml and sustained CD4% >30% (1/61) H: Children who achieved and sustained <400 copies/ml but did not reach <50 copies/ml but did not sustain CD4% >30% (1/61) I: Children who did not achieve <400 copies/ml (failure) but sustained CD4% >30% (3/61) J: Children who did not achieve <400 copies/ml (failure) and did not sustain CD4% >30% (10/61).