HIV May Slip Past Antivirals into Semen

By Mike Bassett,

Contributing Writer,

MedPage Today

May 18, 2017

BOSTON — Antiretroviral therapies may not be as effective at eliminating HIV from semen as they are in eliminating it from blood, researchers reported here.

In an analysis of semen samples from more than 200 HIV-positive men, a significant proportion of those who were on various drug therapy combinations had at least one semen sample turn up positive for the virus: 41% of those whose regimens included an integrase inhibitor with no protease inhibitor; 23% of those whose treatment included a protease inhibitor; and 20% of those whose regimens included a reverse transcriptase inhibitor, according to Robert Eyre, MD, of Beth Israel Deaconess Medical Center and Harvard.

Consequently, HIV in semen remains a serious public health problem, Eyre said at the American Urological Association meeting here.

Eyre noted that phylogenetic analysis of HIV protease gene sequences shows that the virus in blood is derived from different clones than the virus found in semen, “suggesting a highly restricted barrier between the two compartments.” He added that no current treatment regimen kills HIV-infected cells in semen, and that a few published studies of drug levels in semen show that they are about 2% of that achieved in blood.

“It’s very poorly understood that you can get undetectable levels of virus in blood and think you’re totally fine, and yet you can be teeming with virus in semen because the penetration of drug into the semen is so poor,” Eyre told MedPage Today. “There is a discordance between what you see in the blood and what you see in the semen.”

In this study, Eyre and his colleague Ann Kiessling, PhD, of Harvard, reviewed a recently compiled blinded dataset submitted by 230 men from a cohort of more than 500 from the Special Program of Assisted Reproduction, a program designed to help couples achieve a pregnancy without transmitting the father’s infection to the mother or the child. The researchers had data on antiretroviral drug therapy, blood levels of HIV RNA and CD4+ lymphocytes, and HIV RNA or HIV proviral DNA in semen specimens screened from 2012 to 2015.

Eyre and Kiessling found that of the 623 specimens submitted, 112 (18%) tested positive with HIV, with 81 (35%) of the men in the study producing at least one positive specimen.

Ten of 14 men who were not on an antiretroviral therapy (because of persistently low blood virus levels) produced at least one HIV-positive semen specimen with 13 (36%) of specimens testing positive for HIV.

In addition, 28 (20%) of the 137 men who were taking a drug combination that included a reverse transcriptase inhibitor produced at least one HIV-positive specimen and of the 403 specimens in this treatment group, 74 (18%) were positive.

Eighteen (41%) of the 44 men whose treatment included an integrase inhibitor with no protease inhibitor produced at least one HIV-positive specimen with 23 (18%) of the total of 128 specimens testing HIV positive.

And of the 39 men whose therapy included an HIV protease inhibitor, nine produced at least one HIV-positive specimen, with just 11 (10%) of the total of 107 specimens in this group testing positive. This “suggests that treatment that includes a protease inhibitor may be more effective against semen HIV,” Eyre said, although he pointed out the data is incomplete since they’ve only looked at 230 of the 500 men in the study cohort.

“There’s no current treatment regimen that effectively eliminates HIV from semen,” he said. “We certainly need to find out where in the male reproductive tract this virus is hiding out and proliferating.”

He pointed out that a study by Kiessling showed that the epididymis is a principal site of retroviral expression in the mouse. In addition, he said, a study looking at cells in semen after vasectomy show that they are virtually eliminated, which means vasectomy could potentially remove a source of seminal HIV.

“Semen HIV remains a public health problem that is quite serious,” Eyre concluded in his presentation. “Studies to properly analyze the tissue source and determine effective treatment protocols are needed.”

As far as what the findings of this study suggest for practicing urologists and other physicians, Eyre told MedPage Today “they need to understand that someone who comes to you saying they have undetectable virus in their blood doesn’t mean they are disease-free. It means there may be virus in their semen and they could transmit the disease without protected sex.”

filed under: HIV