Lack of Seroconversion and Intact Proviruses in Early-Treated Perinatal HIV

Overview

An adolescent with perinatal HIV treated from 1 month of age exhibited persistent viremia until age 4 but never developed full seroconversion. Despite early treatment and viral suppression, no intact proviruses were detected at ages 11 and 18, challenging current concepts of HIV persistence and remission in children.

Background

Perinatal HIV infection is typically managed with early combined antiretroviral therapy (cART) to limit viral replication and reservoir establishment. Seroconversion, the development of detectable antibodies against HIV, is generally expected following infection. However, this case presents an adolescent who, despite early treatment and prolonged viremia, failed to develop complete seropositivity and showed no intact proviral DNA years later. Understanding such atypical immune and virologic profiles is critical for refining definitions of remission and reservoir dynamics in pediatric HIV.

Data Highlights

Key Findings

• Despite early cART initiation at 1 month, the patient experienced persistent viremia with a peak of 125,000 copies/mL at 41 months due to poor adherence, achieving viral suppression only at 4 years.
• Repeated HIV serologies from 17 months to 18 years were negative or weakly reactive, with incomplete Western blot profiles showing isolated anti-p24 antibodies but no full seroconversion.
• At 11 and 18 years, no intact proviral DNA was detected using an adapted intact proviral DNA assay, although defective proviruses persisted.
• Cell-associated HIV RNA was detectable at very low levels, likely from defective proviruses, indicating minimal transcriptional activity.
• Immunologic assessments at 11 years showed normal CD4 counts and ratios, absence of HIV-specific T-cell responses, and no major innate immune abnormalities.
• The patient demonstrated normal humoral immunity to other pathogens, confirming selective lack of HIV-specific antibody development.

Clinical Implications

This case highlights that early-treated perinatal HIV infection can result in absent or incomplete seroconversion despite prolonged initial viremia, complicating diagnosis and monitoring. The absence of intact proviruses years after treatment suggests potential for reservoir reduction but also challenges current definitions of remission and viral persistence. Clinicians should consider atypical serologic and virologic profiles in early-treated children and the need for sensitive assays to assess reservoir status.

Conclusion

Early initiation of cART in perinatal HIV may lead to unique virologic and immunologic outcomes, including lack of seroconversion and absence of intact proviruses despite initial viremia. These findings call for reevaluation of remission criteria and diagnostic approaches in pediatric HIV.

References

1. Original Article -- Lack of Seroconversion and Intact Proviruses Despite Extended Initial Viremia in an Adolescent with Early-Treated Perinatal HIV Infection