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Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge.

ABSTRACT: OBJECTIVE:Birth diagnosis of HIV-1 infection offers an ideal opportunity for early antiretroviral therapy (ART) to limit HIV-1 reservoir size and limit disease progression. Although data on cellular HIV-1 DNA decay exist for children commencing treatment from 2 to 3 months of age, data are lacking for starting shortly after birth. DESIGN:We studied infants who initiated ART within 8 days after birth to assess HIV-1 DNA levels longitudinally. METHODS:Children were recruited from public health clinics in Cape Town where birth diagnosis of HIV-1 coupled with early ART initiation occurred. Total cellular HIV-1 DNA levels were determined using a sensitive quantitative PCR targeting a conserved region in integrase. RESULTS:Of 11 infants diagnosed and beginning ART within 8 days of birth with detectable pre-ART HIV-1 DNA, three subsequently had undetectable HIV-1 DNA after 6 days, 3 months and 4 months on treatment, respectively. In seven who had virologic suppression (defined as a continuous downward trend in plasma HIV-1 RNA, and <100 copies/ml after 6 months) total HIV-1 DNA continued to decay over 12 months [mean half-life of 64.8 days (95% confidence interval: 47.9-105.7)]. CONCLUSION:In infants initiated on ART within 8 days of life the combination of maternal ART, and early ART for prophylaxis and treatment contribute to rapid decline of HIV-1 infected cells to low or undetectable levels. However, rapid decline of HIV-1 RNA and DNA may complicate definitive diagnosis when confirmatory testing is delayed.

SUBMITTER: Veldsman KA

PROVIDER: S-EPMC5834387 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge.

Veldsman Kirsten A KA Maritz Jean J Isaacs Shahieda S Katusiime Mary G MG Janse van Rensburg Anita A Laughton Barbara B Mellors John W JW Cotton Mark F MF van Zyl Gert U GU

AIDS (London, England) 20180301 5

<h4>Objective</h4>Birth diagnosis of HIV-1 infection offers an ideal opportunity for early antiretroviral therapy (ART) to limit HIV-1 reservoir size and limit disease progression. Although data on cellular HIV-1 DNA decay exist for children commencing treatment from 2 to 3 months of age, data are lacking for starting shortly after birth.<h4>Design</h4>We studied infants who initiated ART within 8 days after birth to assess HIV-1 DNA levels longitudinally.<h4>Methods</h4>Children were recruited ...[more]

PMID: 29334551

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Project description:BackgroundMortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa.Methods and findingsPatients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77).ConclusionsMortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

Project description:BackgroundIn countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial.MethodsHIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy.ResultsAt a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.ConclusionsEarly HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)

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Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge.

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Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge.

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