Better Control of Early Viral Replication Is Associated With Slower Rate of Elicited Antiviral Antibodies in the Detuned Enzyme Immunoassay During Primary HIV-1C Infection

Novitsky, Vladimir MD, PhD*†; Wang, Rui PhD‡; Kebaabetswe, Lemme MSc†; Greenwald, Jamieson AB§; Rossenkhan, Raabya MSc†; Moyo, Sikhulile MSc, MPH†; Musonda, Rosemary PhD*†; Woldegabriel, Elias MD†; Lagakos, Stephen PhD‡; Essex, M DVM, PhD*†

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3181ab6ef0
Epidemiology and Social Science

Background: Estimation of HIV incidence rates is important for timing interventions, planning prevention studies, and monitoring the epidemic. This requires accurate estimation of the “recency period” (also known as the “window period”) between seroconversion and achievement of specific detectable levels of anti-HIV antibody titers, such as the standardized optical density (SOD) in the early phase of HIV-1 infection.

Methods: To obtain a better understanding of interpatient variation of the recency period, prospective measurements of antiviral antibody titers in the early phase of HIV-1 subtype C infection were quantified by Vironostika-LS. Time of seroconversion was estimated by Fiebig staging.

Results: The profiles of SOD values during the first year of infection commonly showed slow initial increase followed by a more rapid increase, although in some patients, SOD values increased rapidly soon after seroconversion. Using an SOD cutoff of 1.0, the average duration of the recency period in subtype C infection in the local epidemic in Botswana was estimated to be 151 days (95% confidence interval: 130 to 172 days) post seroconversion. The recency period was significantly associated (P = 0.007) with the level of viral replication during the first 2-3 months post seroconversion. Reduction of SOD values after initiation of antiretroviral therapy (ART) was a dominant pattern in antiretroviral drug (ARV)-treated subjects.

Conclusions: Our data suggest that HIV incidence estimation based on sensitive/less sensitive enzyme immunoassay cross-sectional testing could be potentially improved by incorporation of viral load levels at the time of detection of a recent infection.

Author Information

From the *Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA; †Botswana-Harvard School of Public Health AIDS Initiative Partnership, Gaborone, Botswana; ‡Department of Biostatistics, Harvard School of Public Health, Boston, MA; and §Harvard College, Faculty of Arts and Sciences, Harvard University, Cambridge, MA.

Received for publication December 9, 2008; accepted March 12, 2009.

The primary HIV-1 subtype C infection study in Botswana, the “Tshedimoso” study, was supported and funded by National Institutes of Health grant R01 AI057027. This work was supported in part by the National Institutes of Health grant D43 TW000004 (R.R.) and R37 AI24643 (R.W. and S.L.) and also through the Fogarty International Clinic Research Scholars and Fellows Program (L.K.).

Correspondence to: M. Essex, DVM, PhD, Chair, Botswana-Harvard School of Public Health AIDS Initiative Partnership, FXB 402, 651 Huntington Avenue, Boston, MA 02115 (e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.