www.hivandhepatitis.com

IAS 2013: HIV May Be Present in Semen Despite Undetectable Blood Viral Load

Gay men with HIV can shed the virus in their semen even when they are on antiretroviral therapy (ART) with fully suppressed blood plasma viral load, according to a longitudinal French study presented at the recent 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur.

Effective ART typically reduces HIV to an undetectable level in the blood within a few months (<50 copies/mL using standard clinical tests). Treatment usually lowers HIV levels in semen and cervical-vaginal fluids as well, and suppressive ART has been shown to reduce the risk of transmission between serodiscordant heterosexual couples by 96%. However, some individuals on ART may still sometimes shed HIV in their semen or other genital fluids. 

Jade Ghosn from Bicetre Hospital in Paris and colleagueslooked at changing levels of HIV in semen from men on ART over time. Most previous data are from cross-sectional studies that measured viral load in paired semen and plasma samples at a single point in time, the researchers noted as background. A previous study of heterosexual men seeking medically assisted conception found a semen shedding rate of 3.1%, but this has not been well studied in men who have sex with men (MSM).

This analysis included 157 HIV positive gay or bisexual men with no symptoms of other sexually transmitted infections (STIs). Their median age was 44 years (range 27 to 67 years), they had been diagnosed with HIV for a median of 10 years, had been on ART for a median of nearly 7 years, and had undetectable viral load (<50 copies/mL) for at least 6 months and a median of about 3 years.

The median current CD4 T-cell count was 637 cells/mm³, but the median nadir (lowest-ever) level was 247 cells/mm³ and 17% had a history of AIDS-defining events. Two-thirds said they had a stable partner (not necessarily exclusive), 63% of those reported outside casual sexual encounters during the past 3 months, and the median number of casual partners during that time was 10.

The researchers collected paired samples of semen and blood at baseline and after 4 weeks. Blood plasma viral load was measured using an ultrasensitive assay that can detect as little as 10 copies/mL. They also performed sperm cultures, measured HIV DNA in peripheral blood mononuclear cells (PBMCs), and tested for STIs including herpes simplex virus type 2 (HSV-2) and syphilis.

Results

• HIV was detectable in 23 out of 304 semen samples, for a prevalence rate of 7.6%.
• The median viral load in detectable semen samples was low, at 145 copies/mL (range 50-1475 copies/mL).
• Blood plasma viral load was detectable in 26% of samples using the ultrasensitive assay.
• Most men (80.3%) had undetectable HIV in their semen at both baseline and week 4.
• However, 21 men had detectable semen HIV at one or both time points:

o   2 (1.3%) had detectable semen HIV both at baseline and at week 4;

o   5 (3.2%) had detectable semen HIV at baseline but not at week 4;

o   14 (8.9%) had undetectable semen HIV at baseline that became detectable at week 4.

• 32 participants (20.5%) were found to have asymptomatic STIs at baseline (including 2 men with 2 STIs each):

o   1 with Mycoplasma;

o   2 with gonorrhea;

o   3 with chlamydia;

o   4 with Gardnerella vaginalis;

o   6 with syphilis;

o   18 with Ureaplasma urealyticum.

• The only significant predictor of semen HIV shedding was higher intracellular HIV DNA levels in PBMCs (odds ratio 3.1 -- or 3-fold higher risk -- for HIV DNA >318 [or 2.5 log] copies/million PBMCs).
• There was no association between detectable semen viral load and duration of undetectable blood viral load, low level blood viral load using the ultrasensitive test, ART adherence, current or nadir CD4 cell count, presence of other STIs, or number of sexual partners.

"We show that HIV RNA can be detected in semen of HIV-1 infected MSM despite sustained successful [combination] ART, with a significantly higher prevalence than in heterosexual men" (7.6% vs 3.1%), the researchers concluded based on this "first longitudinal study focusing on HIV-infected MSM with sustained viral suppression in blood plasma and no symptom of genital infection."

"The shedding was intermittent and not associated with the presence of an asymptomatic STI," they added. "Whether such levels of [semen viral load] are infectious remains to be determined."

8/21/13

Reference

J Ghosn, A Delobelle, M Leruez-Ville, et al. HIV shedding in semen of men who have sex with men on efficient cART is associated with high HIV-DNA levels in PBMC but not with residual HIV-RNA viremia (ANRS EP49). 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract MOPE142.