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Cross-sectional detection of acute HIV infection: timing of transmission, inflammation and antiretroviral therapy.

Gay C, Dibben O, Anderson JA, Stacey A, Mayo AJ, Norris PJ, Kuruc JD, Salazar-Gonzalez JF, Li H, Keele BF, Hicks C, Margolis D, Ferrari G, Haynes B, Swanstrom R, Shaw GM, Hahn BH, Eron JJ, Borrow P, Cohen MS - PLoS ONE (2011)

Bottom Line: Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.The results emphasize the difficulty in recruiting subjects early in AHI.Regardless of aggressive screening, peak viremia and inflammation occurred before enrollment and potential intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America. cynthia_gay@med.unc.edu

ABSTRACT

Background: Acute HIV infection (AHI) is a critical phase of infection when irreparable damage to the immune system occurs and subjects are very infectious. We studied subjects with AHI prospectively to develop better treatment and public health interventions.

Methods: Cross-sectional screening was employed to detect HIV RNA positive, antibody negative subjects. Date of HIV acquisition was estimated from clinical history and correlated with sequence diversity assessed by single genome amplification (SGA). Twenty-two cytokines/chemokines were measured from enrollment through week 24.

Results: Thirty-seven AHI subjects were studied. In 7 participants with limited exposure windows, the median exposure to HIV occurred 14 days before symptom onset. Lack of viral sequence diversification confirmed the short duration of infection. Transmission dates estimated by SGA/sequencing using molecular clock models correlated with transmission dates estimated by symptom onset in individuals infected with single HIV variants (mean of 28 versus 33 days). Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.

Discussion: The results emphasize the difficulty in recruiting subjects early in AHI. Viral sequence diversity proved accurate in estimating time of infection. Regardless of aggressive screening, peak viremia and inflammation occurred before enrollment and potential intervention. Given the personal and public health importance, improved AHI detection is urgently needed.

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Related in: MedlinePlus

Timeline of AHI: estimated HIV exposure, symptom onset, presentation to care, AHI diagnosis and enrollment in subjects with a narrow window of exposure based on self-report.A narrow window of exposure is defined as all patients with high or medium exposure date confidence (n = 6), plus patients with a one-time exposure in the 8 weeks prior to diagnosis with a partner of unknown status (n = 4).
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pone-0019617-g001: Timeline of AHI: estimated HIV exposure, symptom onset, presentation to care, AHI diagnosis and enrollment in subjects with a narrow window of exposure based on self-report.A narrow window of exposure is defined as all patients with high or medium exposure date confidence (n = 6), plus patients with a one-time exposure in the 8 weeks prior to diagnosis with a partner of unknown status (n = 4).

Mentions: Given the desire to identify subjects as quickly as possible after infection, we attempted to estimate the date of exposure. Over one-third were evaluated at a medical facility prior to AHI diagnosis, representing missed opportunities for earlier diagnosis. Figure 1 depicts the timeline of exposures, symptom onset, presentation-to-care, AHI diagnosis and enrollment for subjects with a relatively narrow exposure window. From the date of blood draw, the mean turn-around time for NAT pooling results during the study period was 12 days (range 2 to 41). Four transmission pairs were confirmed by SGA and DNA sequencing; however, multiple sexual exposures occurred with two confirmed transmission partners (not shown), precluding establishment of an exposure date. Subject 3 (Figure 1) reported only one exposure on the date of enrollment. Subject 1 reported a one-time exposure with a confirmed transmission partner occurring 16 days before symptom onset. Using the midpoints of exposure windows for 7 of 10 subjects with relatively narrow exposure windows (subjects 3, 4 and 6 were excluded), median estimated exposure to HIV occurred 14 days before symptom onset (range 9–21 days, IQR 12–17).


Cross-sectional detection of acute HIV infection: timing of transmission, inflammation and antiretroviral therapy.

Gay C, Dibben O, Anderson JA, Stacey A, Mayo AJ, Norris PJ, Kuruc JD, Salazar-Gonzalez JF, Li H, Keele BF, Hicks C, Margolis D, Ferrari G, Haynes B, Swanstrom R, Shaw GM, Hahn BH, Eron JJ, Borrow P, Cohen MS - PLoS ONE (2011)

Timeline of AHI: estimated HIV exposure, symptom onset, presentation to care, AHI diagnosis and enrollment in subjects with a narrow window of exposure based on self-report.A narrow window of exposure is defined as all patients with high or medium exposure date confidence (n = 6), plus patients with a one-time exposure in the 8 weeks prior to diagnosis with a partner of unknown status (n = 4).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3091862&req=5

pone-0019617-g001: Timeline of AHI: estimated HIV exposure, symptom onset, presentation to care, AHI diagnosis and enrollment in subjects with a narrow window of exposure based on self-report.A narrow window of exposure is defined as all patients with high or medium exposure date confidence (n = 6), plus patients with a one-time exposure in the 8 weeks prior to diagnosis with a partner of unknown status (n = 4).
Mentions: Given the desire to identify subjects as quickly as possible after infection, we attempted to estimate the date of exposure. Over one-third were evaluated at a medical facility prior to AHI diagnosis, representing missed opportunities for earlier diagnosis. Figure 1 depicts the timeline of exposures, symptom onset, presentation-to-care, AHI diagnosis and enrollment for subjects with a relatively narrow exposure window. From the date of blood draw, the mean turn-around time for NAT pooling results during the study period was 12 days (range 2 to 41). Four transmission pairs were confirmed by SGA and DNA sequencing; however, multiple sexual exposures occurred with two confirmed transmission partners (not shown), precluding establishment of an exposure date. Subject 3 (Figure 1) reported only one exposure on the date of enrollment. Subject 1 reported a one-time exposure with a confirmed transmission partner occurring 16 days before symptom onset. Using the midpoints of exposure windows for 7 of 10 subjects with relatively narrow exposure windows (subjects 3, 4 and 6 were excluded), median estimated exposure to HIV occurred 14 days before symptom onset (range 9–21 days, IQR 12–17).

Bottom Line: Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.The results emphasize the difficulty in recruiting subjects early in AHI.Regardless of aggressive screening, peak viremia and inflammation occurred before enrollment and potential intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America. cynthia_gay@med.unc.edu

ABSTRACT

Background: Acute HIV infection (AHI) is a critical phase of infection when irreparable damage to the immune system occurs and subjects are very infectious. We studied subjects with AHI prospectively to develop better treatment and public health interventions.

Methods: Cross-sectional screening was employed to detect HIV RNA positive, antibody negative subjects. Date of HIV acquisition was estimated from clinical history and correlated with sequence diversity assessed by single genome amplification (SGA). Twenty-two cytokines/chemokines were measured from enrollment through week 24.

Results: Thirty-seven AHI subjects were studied. In 7 participants with limited exposure windows, the median exposure to HIV occurred 14 days before symptom onset. Lack of viral sequence diversification confirmed the short duration of infection. Transmission dates estimated by SGA/sequencing using molecular clock models correlated with transmission dates estimated by symptom onset in individuals infected with single HIV variants (mean of 28 versus 33 days). Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.

Discussion: The results emphasize the difficulty in recruiting subjects early in AHI. Viral sequence diversity proved accurate in estimating time of infection. Regardless of aggressive screening, peak viremia and inflammation occurred before enrollment and potential intervention. Given the personal and public health importance, improved AHI detection is urgently needed.

Show MeSH
Related in: MedlinePlus