TY - JOUR
T1 - Validation of the Limiting Antigen Avidity Assay to Estimate Level and Trends in HIV Incidence in an A/D Epidemic in Rakai, Uganda
AU - Laeyendecker, Oliver
AU - Gray, Ronald H.
AU - Grabowski, M. Kate
AU - Reynolds, Steven J.
AU - Ndyanabo, Anthony
AU - Ssekasanvu, Joseph
AU - Fernandez, Reinaldo E.
AU - Wawer, Maria J.
AU - Serwadda, David
AU - Quinn, Thomas C.
N1 - Funding Information:
This research was supported by the National Institute of Mental Health (R01MH107275), the National Institute of Allergy and Infectious Diseases (5R01 AI095068, 1R01AI128779-01, R01AI110324, K01AI125086), and Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, and the Johns Hopkins University Center for AIDS Research (P30AI094189). This work was also supported (in part) by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Child Health and Human Development (NICH/HD), National Institute on Drug Abuse, National Institute of Mental Health, and Office of Aids Research, of the NIH, DHHS (UM1 AI068613). We also thank the Rakai Community Cohort Study participants and study team.
Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.
PY - 2019/4
Y1 - 2019/4
N2 - The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 copies/mL is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Sera from persons seen in two surveys (2008-2009 and 2012-2013) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0%, was compared with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95% confidence interval (CI) 0.90-1.23] in 2008-2009 and 0.66/100 py (95% CI 0.52-0.83) in 2012-2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95% CI 0.97-2.30) in 2008-2009 and 2.55/100 py (95% CI 1.51-3.59) in 2012-2013 (a significant increase, p < .05.) However, using a subtype-specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95% CI 0.44-1.33) in 2008-2009 and 0.67% (95% CI 0.00-1.68) in 2012-2013, approximating to the observed incidence trends. In this subtype A/D epidemic, the per protocol LAg-Avidity + VL assay overestimated HIV incidence and failed to detect declines in incidence. Adjustment for FRR, MDRI, and subtype distribution provided incidence estimates similar to empirically observed incidence level and trends. Thus, use of the LAg-Avidity assay in an A/D epidemic requires adjustment for subtype.
AB - The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 copies/mL is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Sera from persons seen in two surveys (2008-2009 and 2012-2013) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0%, was compared with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95% confidence interval (CI) 0.90-1.23] in 2008-2009 and 0.66/100 py (95% CI 0.52-0.83) in 2012-2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95% CI 0.97-2.30) in 2008-2009 and 2.55/100 py (95% CI 1.51-3.59) in 2012-2013 (a significant increase, p < .05.) However, using a subtype-specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95% CI 0.44-1.33) in 2008-2009 and 0.67% (95% CI 0.00-1.68) in 2012-2013, approximating to the observed incidence trends. In this subtype A/D epidemic, the per protocol LAg-Avidity + VL assay overestimated HIV incidence and failed to detect declines in incidence. Adjustment for FRR, MDRI, and subtype distribution provided incidence estimates similar to empirically observed incidence level and trends. Thus, use of the LAg-Avidity assay in an A/D epidemic requires adjustment for subtype.
KW - Uganda
KW - cross-sectional incidence estimation
KW - incidence
KW - validation
UR - http://www.scopus.com/inward/record.url?scp=85063814269&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063814269&partnerID=8YFLogxK
U2 - 10.1089/aid.2018.0207
DO - 10.1089/aid.2018.0207
M3 - Article
C2 - 30560723
AN - SCOPUS:85063814269
SN - 0889-2229
VL - 35
SP - 364
EP - 367
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 4
ER -