Review and feature article
Absence of detectable viremia in a perinatally HIV-1–infected teenager after discontinuation of antiretroviral therapy

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A 15-year-old girl with perinatal HIV-1 infection has remained asymptomatic with undetectable plasma HIV-1 viremia for more than 5 years after discontinuing all antiretroviral therapy. Viral sequence analysis of proviral HIV-1 DNA revealed no evident fitness-attenuating deletions or mutations. This subject exhibited an unusually robust HIV-specific T-cell response, with an intact CD4+ T cell–proliferative response to HIV-1 antigens. In addition, the subject was found to be heterozygous for the 32-bp deletion in the CCR5 gene, which encodes the primary coreceptor for HIV-1 entry into cells. This mutation mediates profound resistance to HIV infection in homozygotes and has been associated with delayed disease progression in heterozygotes after both horizontal and vertical HIV-1 infection. Although adults with long-term nonprogressive HIV disease have been studied at length, there is no prior description in the literature of a perinatally HIV-infected child whose plasma HIV-1 viremia is controlled to undetectable levels in the absence of antiretroviral therapy.

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Case presentation

A 15-year-old African American girl presented to the Infectious Disease Clinic at Children's Hospital in Boston, Massachusetts, with asymptomatic vertically acquired HIV-1 infection. The patient was born to a mother with known HIV-1 infection who had received no antiretroviral prophylaxis in the perinatal period. The child's HIV-1 ELISA and Western Blot test results remained positive at 18 months of age, and she was therefore judged to be HIV-1 infected. At that time (in 1991), she began

Differential diagnosis

Although rare, spontaneous control of HIV viremia has been well described in the adult population.1 However, lack of detectable plasma viremia in the absence of therapy has not previously been reported in a perinatally HIV-1–infected child. Much of our current understanding of the factors that govern the rate of progression to AIDS has come through the study of adult long-term nonprogressors who maintain very low viral loads in the absence of therapy. Long-term nonprogressive HIV-1 infection

Laboratory testing

Viral, immunologic, and genetic factors were all considered potential contributors to the unusual clinical phenotype of our patient. Full-genome viral sequencing was performed with previously described PCR primers and conditions to rule out the possibility that the patient was infected with an attenuated strain of HIV-1.42 The virus was readily amplified from proviral DNA extracted from PBMCs at age 12.1 years, and no deletions or previously described fitness-attenuating polymorphisms were

Pathogenesis

Detailed laboratory analysis of this patient revealed a disease-attenuating genetic polymorphism, as well as an unusually robust HIV-specific CD4+ T-cell response, both of which could be contributing to the low level of viremia observed in this child. The patient was found to be heterozygous for a deletion in the CCR5 chemokine receptor gene, which encodes the principal cellular coreceptor for HIV-1 entry into cells. Heterozygosity for this CCR5Δ32 polymorphism leads to diminished cell-surface

Summary statement

This case serves as a reminder that the clinical course of HIV-1 disease is extremely heterogeneous, and multiple viral and host factors play a role in determining the rate of progression to AIDS. Although HIV infection remains, at present, an incurable illness, an increasing number of HIV-1–infected patients have been identified who remain asymptomatic well into the second or third decade of infection, including many patients who were infected perinatally. However, control of HIV viremia to

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    Supported by the National Institutes of Health (K23-AI52078, M.E.F.), the Elizabeth Glaser Pediatric AIDS Foundation (M.E.F.), and the Harvard Medical School Center for AIDS Research. M.E.F. is an Elizabeth Glaser Scientist of the Elizabeth Glaser Pediatric AIDS Foundation.

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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