Association of recent HIV infection and in-utero HIV-1 transmission

Abstract

Objective: We previously developed a multiassay algorithm (MAA) to identify recent HIV infection that includes the BED-capture enzyme immunoassay, an avidity assay based on the Genetic Systems HIV-1/HIV-2 + O enzyme immunoassay, CD4 cell count, and HIV viral load. We used this MAA to evaluate the association between recent maternal HIV infection and in-utero transmission of HIV.

Methods: Plasma samples were collected at delivery from 2561 HIV-infected women in the postexposure prophylaxis of infants-Malawi trial. The MAA described above was used to identify women with recent HIV infection. Logistic regression models assessed association between recent HIV infection and in-utero HIV transmission (defined as a positive infant HIV DNA test at birth).

Results: Seventy-three women were identified as recently infected using the MAA. Those women were younger and had lower parity than women who were identified as not recently infected using the MAA (P < 0.0001 for age and parity). The frequency of in-utero HIV transmission was 17.8% among women identified as recently infected, compared with 6.7% among women identified as not recently infected (13/73 vs. 166/2488, P = 0.001). In a multivariate model, three factors were independently associated with in-utero HIV transmission: recent infection [adjusted odds ratio (AOR): 2.49, 95% confidence interval (CI): 1.30-4.78, P = 0.006], log(10) HIV viral load at delivery (AOR: 2.01, 95% CI: 1.60-2.51, P < 0.0001), and younger age (per 10 year increase, AOR: 0.66, 95% CI: 0.43-0.93, P = 0.02).

Conclusion: Results obtained using a MAA suggest that recent maternal HIV acquisition is strongly associated with in-utero HIV transmission, independent of HIV viral load at delivery.

Figure 1. Use of a multi-assay algorithm (MAA) to identify women with recent HIV infection

A multi-assay algorithm (MAA) was used to identify women in the PEPI-Malawi trial who were recently infected with HIV at the time of delivery. In the MAA, women are classified as recently infected if they have the following test results: BED result < 1.0 optical density units (OD-n) + avidity result < 80% + CD4 cell count > 200 cells/mm³ + HIV viral load > 400 copies/ml. The assay cut-offs used for BED and avidity assays in this MAA (1.0 OD-n and 80%, respectively) are higher than the assay cut-offs that are typically used when each these assays is used alone for cross-sectional incidence testing (see below). Most of the women tested (2479/2561=96.8%) were classified as not recently infected based on results from the BED and avidity assays; those women either had a BED assay result >1.0 (N=175), an avidity assay result >80% (N=44) or both (N=2,260). The remaining 82 women had BED and avidity test results below the assay cut-offs, but were classified as not recently infected because they had either a CD4 cell count < 200 cells/mm³ (N=5) or an HIV viral load < 400 copies/ml (N=4). The remaining 73 women (2.9 % of the 2,561 women tested) were classified as recently infected using the MAA.