Experimental infection with Haemophilus ducreyi in persons who are infected with HIV does not cause local or augment systemic viral replication

Abstract

We infected 11 HIV-seropositive volunteers whose CD4(+) cell counts were >350 cells/ microL (7 of whom were receiving antiretrovirals) with Haemophilus ducreyi. The papule and pustule formation rates were similar to those observed in HIV-seronegative historical control subjects. No subject experienced a sustained change in CD4(+) cell count or HIV RNA level. The cellular infiltrate in biopsy samples obtained from the HIV-seropositive and HIV-seronegative subjects did not differ with respect to the percentage of leukocytes, neutrophils, macrophages, or T cells. The CD4(+):CD8(+) cell ratio in biopsy samples from the HIV-seropositive subjects was 1:3, the inverse of the ratio seen in the HIV-seronegative subjects (P<.0001). Although CD4(+) cells proliferated in lesions, in situ hybridization and reverse-transcription polymerase chain reaction for HIV RNA was negative. We conclude that experimental infection in HIV-seropositive persons is clinically similar to infection in HIV-seronegative persons and does not cause local or augment systemic viral replication. Thus, prompt treatment of chancroid may abrogate increases in viral replication associated with natural disease.

Figure 1

CD4⁺ cell counts and viral loads for HIV-infected volunteers. A, CD4⁺ cell counts for all HIV-infected volunteers, measured at time points 0 (before inoculation), 1 (clinical end point), 2 (28 days after inoculation), and 3 (42–56 days after inoculation). B, HIV RNA levels for the 3 HIV-infected volunteers not receiving highly active antiretroviral therapy (HAART), measured at the same time points as CD4⁺ cell counts. The 7 volunteers who were receiving HAART maintained viral loads of <50 copies/mL throughout the study.

Figure 2

Nos. of leukocytes, neutrophils, macrophages, T cells, and B cells, analyzed by flow cytometry, in biopsy samples of pustules from HIV-seronegative (A) and HIV-infected (B) volunteers. Data for the HIV-seronegative subjects (which have been published previously [42]) were adjusted by a factor of 1.44, to account for the smaller biopsy sample sizes (5 mm) versus those (6 mm) for the HIV-infected subjects.

Figure 3

CD4⁺ and CD8⁺ cell counts, expressed as a percentage of the CD3⁺ cell population, in blood and biopsy samples from HIV-seronegative (A) and HIV-infected (B) volunteers. Data for the HIV-seronegative subjects have been published previously [42].

Figure 4

Hematoxylineosin staining of lesional infiltrate caused by experimental infection with 35000HP in an HIV-seronegative (A) and an HIV-infected (B) volunteer. Original magnification, ×25 (for both). Double labeling for perforin (blue) and CD8 (red) in a biopsy sample from an HIV-seronegative subject (C) and an HIV-infected subject (D) demonstrate that cytolytic CD8⁺ cells (arrows) are found in experimentally infected skin. Original magnification, ×100 (for both). DC-LAMP⁺ (E; red) and CD83⁺ (F; red) cells in the epidermis of a biopsy sample from an HIV-infected subject suggests ongoing maturation of dendritic cells during experimental infection with Haemophilus ducreyi. Double labeling for CD4⁺ or CD8⁺ cells (brown) and the proliferation antigen MIB-1 (blue) demonstrate proliferating CD4⁺ cells (G; arrows) and proliferating CD8⁺ cells (H; arrows) in the dermis of biopsy samples from HIV-infected subjects. Original magnification, ×160 (for both).