Genital ulcers frequently associated with HIV shedding in men

HIV was detected in the lesions of almost 50% of HIV-positive men with genital ulcer disease, investigators report in the April 1^st edition of Clinical Infectious Diseases.

A higher viral load, larger lesions, multiple ulcers, and weeping ulcers were all associated with an increased risk of HIV being shed by the ulcers.

“Our study showed the presence of lesional HIV in almost half of the HIV-positive men, which underscores the importance of GUD on increasing HIV infectivity,” write the authors.

A number of studies have shown that there is a higher risk of HIV transmission if one or both sex partners have genital ulcers. Ulcers can provide a portal of entry for the virus, and the inflammation associated with them can result in the presence of a large number of CD4 and other immune cells which are targeted by HIV. In HIV-positive individuals, the virus may be present in the ulcers.

In the Rakai study of serodiscordant couples, investigators found that the only two factors significantly associated with an increased risk of HIV transmission were viral load and genital ulcers.

Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcers, and both symptomatic and asymptomatic HSV-2 have been shown to increase HIV shedding in individuals co-infected with both viruses.

Biopsies taken from the genital lesions of co-infected individuals showed that HSV-2 causes inflammation in the skin below healed ulcers, and that cells with the co-receptors targeted by HIV are present in large numbers.

A British-lead team of investigators monitored HIV and HSV-2 shedding in the genital lesions of co-infected men in South Africa. They examined the factors associated with HIV shedding in lesions.

The research involved 387 HIV-positive men with genitals ulcers who, between 2005 and 2006, were enrolled in a study to see if taking suppressive HSV-2 therapy reduced the risk of HIV transmission. This study (NCT00164424) showed that this therapy was not an effective method of HIV prevention.

Using a questionnaire, information was collected on demographics, sexual behaviour and ulcer characteristics.

Lavage and swabs were used to monitor HIV and HSV-2 shedding.

A series of statistical analyses were performed to determine the factors associated with an increased risk of HIV and HSV-2 shedding in genital ulcers.

The men had an average age of 32 years. Their median CD4 cell count was 282 cells/mm³, with median viral load being 87,200 copies/ml.

HIV was detected in the genital ulcers of 173 (46%) men. This included one man who was taking antiretroviral therapy and had an undetectable plasma viral load.

Mean plasma viral load was 0.44 log₁₀/ml higher in men who had detectable HIV in genital ulcers than those who did not. This difference was significant (p < 0.001). The investigators also found a significant correlation between the presence of HIV in genital ulcers and a higher plasma viral load (p < 0.001) and a lower CD4 cell count (p < 0.001).

Statistical analysis that controlled for potentially confounding factors showed that the factors associated with an increased risk of HIV being present in genital ulcers were:

• Higher plasma viral load (OR, 2.5; 95% CI, 1.7-3.5, p < 0.001).
• Lesions with larger dimensions (OR, 2.5; 95% CI, 1.5-4.2, p < 0.001).
• Weeping ulcers (OR, 2.2; 95% CI, 1.1-4.2, p = 0.02).
• Five or more ulcers (OR, 3.6; 95% CI, 1.6-8.4, p = 0.02).

The investigators found infection with Trichomonas vaginalis was associated with an increased risk of shedding HIV in lesions (p = 0.027).

Amongst the men with HIV present in their genital ulcers, the investigators found that this was correlated with HSV-2 load in these ulcers (p = 0.02), a higher plasma HIV viral load (p < 0.01) and a lower CD4 cell count (p = 0.01).

“We found that men with larger lesions, purulent and multiple ulcers, higher plasma viral loads, and HSV-2 sero-positivity were at increased odds of HIV-1 shedding,” comment the investigators.

They conclude “the findings from this and other studies suggest that patients with genital ulcers are a key population to intervene for HIV prevention.”