http://www.cdc.gov/hiv/prevention/resear ch/art/
What is the Risk of Sexual HIV Transmission for HIV-infected Persons With Undetectable Viral Load?
ART is considered effective when it consistently suppresses plasma viral load to undetectable levels. However, sexual transmission of HIV from an infected partner who was on ART with a repeatedly undetectable plasma viral load has been documented.8 An infected partner's genital (seminal or vaginal) fluid viral load may play a greater role than plasma viral load when evaluating the risk of sexual transmission of HIV. The likelihood of HIV transmission in the setting of ART is influenced by a number of factors, several of which are described below.
The Meaning of “Undetectable” Viral Load: Persistence of Virus in Plasma and Seminal Fluid
Periodic blood plasma viral load monitoring is used to measure ART effectiveness. The goal of effective ART is the long-term suppression of plasma viral load, usually defined as the maintenance of a level of HIV virus that is below the threshold detectable by available tests. While plasma viral load tests are reliable, they have limitations: virus levels below a minimum concentration may not be detected. Studies have shown that persistent virus is found in peripheral blood mononuclear cells9, 10 even when individuals have sustained undetectable plasma viral load levels.
Genital fluid viral loads are not routinely measured in persons on ART. Although ART reduces concentration of virus in seminal fluid,11 virus persists within cells present in seminal fluid of some men who are on ART with undetectable plasma viral load.12-13 ART also is associated with decrease in cervicovaginal fluid viral load; however, ‘breakthrough' shedding has been observed in some studies.14-17 Therefore, the potential for transmission exists despite sustaining undetectable viral load while on effective ART.
Transient Increases (“Blips”) in Viral Load
Several studies have observed that individuals on effective ART who achieve long-term suppression of viral load to undetectable levels may exhibit periodic temporary increases in plasma viral load (blips). These are generally small increases ( between approximately 50 and 1000 copies/mL), and are estimated to last for short periods (<3 and="" are="" be="" because="" blips.="" conceivable="" correlate="" currently="" data="" enhanced="" fluid="" genital="" however="" in="" increases="" insufficient="" is="" it="" load="" magnitude="" make="" may="" might="" missed="" nature="" of="" on="" regarding="" related="" risk.="" risk="" routine="" sexual="" span="" statements="" testing.="" that="" the="" there="" they="" to="" transient="" transmission="" viral="" weeks="" with="">
Correlation Between Plasma and Genital Fluid Viral Load and Resistance to ART
Although ART reduces viral load in both plasma and seminal fluid, undetectable plasma viral load may not always predict undetectable seminal fluid viral load. A recent review of 19 studies, which compared plasma and seminal fluid viral loads, indicates that while blood and genital fluid viral load are often correlated, this is not always the case.21 Thus, a person with an undetectable plasma viral load may still shed virus in genital fluid at higher levels, which poses risk for transmission.
Several additional factors may affect genital fluid viral load. For example, sexually transmitted infections (STIs) such as gonorrhea and chlamydia have been shown to transiently increase viral load in genital fluids.22-23 Individuals with active STIs may therefore be more infectious, despite a low or undetectable plasma viral load. Moreover, as individuals with STIs may not have any symptoms, it may be impossible for either partner to be aware of this increased risk.
Some of the variation in genital fluid viral load may be due to differences in the degree to which different ART medications enter genital fluid. Recently developed research methods allow for measurement of drug concentrations in seminal and vaginal fluids, which can then be compared to drug levels measured in blood. This research has found that some ART medications achieve higher concentrations in genital fluids than others.24-27 For instance, nucleoside/tide reverse transcriptase inhibitors (NRTIs) penetrate to a greater extent in male and female genital secretions than do protease inhibitors (PIs). Further work of this type may eventually aid in selection of antiretroviral medications in order to reduce sexual transmission. However, more data collected via these methods and better understanding of the degree to which this approach might be effective is needed before specific recommendations can be made.
In addition to differences in viral load between plasma and genital fluids, there may also be differences in the resistance characteristics of virus in these two locations. HIV may become resistant to ART medications through mutations that occur during replication and through exposure to insufficient or inconsistent levels of HIV medications. This may happen when ART medications are not taken according to the prescribed schedule or doses are skipped. In addition, drugs which do not enter the genital fluid as well may help promote the development of resistance in the genital fluid specifically. Some researchers have noted that within an individual, the resistance characteristics of virus isolated from genital fluid may differ from those of virus isolated from plasma.28-30
In summary, for couples in which one member is HIV-infected, treatment of the infected partner with effective ART and suppression of viral load to undetectable levels should greatly reduce the risk of transmission to the uninfected partner. However, this risk is not eliminated and it may not be maximally reduced at all times due to some of the factors discussed above. Moreover, the likelihood of transmission may be expected to increase with repeated exposures over time. In a model which estimated transmission risk in the setting of suppressed viral load (<50 10="" 11="" 215="" 3="" 425="" 5="" 70="" a="" additional="" among="" analysis="" and="" art="" be="" chance="" cohorts="" compatible="" condoms="" copies="" couples="" data="" e.g.="" estimated="" event="" events="" expected="" female-to-male="" for="" from="" further="" heterosexual="" however="" important="" in="" including="" individual="" intercurrent="" is="" it="" load="" male-to-female="" male-to="" male="" meta-analysis="" methods="" minimize="" ml="" no="" number="" observed="" occurring="" of="" one="" order="" over="" per="" person-years.32="" persons="" population="" possibility="" preventive="" reason="" receiving="" recognize="" risk="" serodiscordant="" span="" stis="" that="" the="" this="" to="" transmission.="" transmission="" transmissions.31="" transmissions="" use="" viral="" was="" with="" within="" without="" years="">
Monday, October 28, 2013
A couple of post from articles about transmission risks for men with HIV who have "undetectable" viral loads
" 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
In the first study to track HIV shedding in semen over time in men who have sex with men (MSM) with sustained HIV suppression in blood, 7.6% of men with undetectable virus in blood had intermittent shedding in semen that was not linked to an asymptomatic sexually transmitted infection (STI) [1]. HIV levels in peripheral blood mononuclear cells (PBMCs) predicted HIV detection in semen.
Research shows that an undetectable viral load in plasma does not guarantee an undetectable load in semen--and therefore may not eliminate the risk of sexual HIV transmission. But most data on this issue come from cross-sectional studies involving heterosexual men in medically assisted reproductive programs. A French team conducted this study to address these questions in a longitudinal study involving MSM.
The study involved HIV-positive adult MSM on a stable antiretroviral regimen with a plasma viral load below 50 copies for at least 6 months. No men had clinical symptoms of an STI, and all agreed to abstain from sex for 48 hours before giving semen and blood samples. The researchers collected paired semen and blood samples at a baseline visit and 4 weeks later. They also measured PBMC-associated HIV DNA and tested men for syphilis and other STIs. Based on a 3% to 5% rate of genital HIV shedding in heterosexual men, the investigators calculated that they would need 150 men to find at least one blood-semen discordance if prevalence was as low as 3%.
The researchers recruited 153 MSM with a median age of 44 years (range 27 to 67). Median time since HIV diagnosis was 10.4 years, and median nadir and current CD4 counts were 247 and 637. Median PBMC HIV DNA stood at 229 copies per million cells (range 70 to 2099). These men had taken a stable antiretroviral regimen for a median 2.1 years (range 0.3 to 12.4) and had an undetectable viral load for a median 3.3 years (range 0.5 to 13.7). Almost two thirds of men (63%) had a stable partner, though 63% with a stable partner also had casual sex with a median of 10 other men in the past 3 months (range 1 to 160).
HIV could be detected in 23 of 304 semen samples at a median level of 145 copies/mL (range 50 to 1475) to yield a prevalence of 7.6%. Five men (3.2%) had HIV detectable in semen at the baseline visit but not week 4, while 2 (1.3%) had HIV detectable in semen at both visits, and 14 (9.1%) had HIV detectable at week 4 but not the baseline visit. HIV could not be detected in 74% of semen samples by an ultrasensitive assay.
Thirty-two of 157 men (20.4%) had an asymptomatic STI detected, and 2 men had two STIs. Ureaplasma urealyticum was the most frequent STI, affecting 18 men, followed by syphilis in 6, Gardnerella vaginalis in 4, Chlamydia trachomatis is 3, and Neisseria gonorrhoeae in 2.
Multivariate analysis identified two factors associated with detectable HIV in semen: A current CD4 count between 554 and 735, compared with a lower count, cut the odds of HIV in semen 70% (odds ratio 0.3, 95% confidence interval [CI] 0.1 to 0.9, P = 0.027). And HIV DNA in PBMCs above versus below 318 copies per million cells tripled the odds (odds ratio 3.1, 95% CI 1.2 to 7.7, P = 0.015). HIV detection in semen was not associated with STIs, CDC stage, nadir or current CD4 count, duration of undetectable HIV in plasma, adherence to antiretroviral therapy, or number of sex partners.
The researchers noted that seminal HIV prevalence in this study was significantly higher than in a recent cross-sectional study of heterosexual French men (7.6% versus 3.1%, P = 0.016) [2]. Whether these levels of HIV in semen are infectious, they added, remains to be determined. "
1. There is viable HIV in the semen of many men who have "undetectable" viral loads.
2. How big a risk for infection this presents is unknown, but I'd be it's not zero.
Mark Mascolini
In the first study to track HIV shedding in semen over time in men who have sex with men (MSM) with sustained HIV suppression in blood, 7.6% of men with undetectable virus in blood had intermittent shedding in semen that was not linked to an asymptomatic sexually transmitted infection (STI) [1]. HIV levels in peripheral blood mononuclear cells (PBMCs) predicted HIV detection in semen.
Research shows that an undetectable viral load in plasma does not guarantee an undetectable load in semen--and therefore may not eliminate the risk of sexual HIV transmission. But most data on this issue come from cross-sectional studies involving heterosexual men in medically assisted reproductive programs. A French team conducted this study to address these questions in a longitudinal study involving MSM.
The study involved HIV-positive adult MSM on a stable antiretroviral regimen with a plasma viral load below 50 copies for at least 6 months. No men had clinical symptoms of an STI, and all agreed to abstain from sex for 48 hours before giving semen and blood samples. The researchers collected paired semen and blood samples at a baseline visit and 4 weeks later. They also measured PBMC-associated HIV DNA and tested men for syphilis and other STIs. Based on a 3% to 5% rate of genital HIV shedding in heterosexual men, the investigators calculated that they would need 150 men to find at least one blood-semen discordance if prevalence was as low as 3%.
The researchers recruited 153 MSM with a median age of 44 years (range 27 to 67). Median time since HIV diagnosis was 10.4 years, and median nadir and current CD4 counts were 247 and 637. Median PBMC HIV DNA stood at 229 copies per million cells (range 70 to 2099). These men had taken a stable antiretroviral regimen for a median 2.1 years (range 0.3 to 12.4) and had an undetectable viral load for a median 3.3 years (range 0.5 to 13.7). Almost two thirds of men (63%) had a stable partner, though 63% with a stable partner also had casual sex with a median of 10 other men in the past 3 months (range 1 to 160).
HIV could be detected in 23 of 304 semen samples at a median level of 145 copies/mL (range 50 to 1475) to yield a prevalence of 7.6%. Five men (3.2%) had HIV detectable in semen at the baseline visit but not week 4, while 2 (1.3%) had HIV detectable in semen at both visits, and 14 (9.1%) had HIV detectable at week 4 but not the baseline visit. HIV could not be detected in 74% of semen samples by an ultrasensitive assay.
Thirty-two of 157 men (20.4%) had an asymptomatic STI detected, and 2 men had two STIs. Ureaplasma urealyticum was the most frequent STI, affecting 18 men, followed by syphilis in 6, Gardnerella vaginalis in 4, Chlamydia trachomatis is 3, and Neisseria gonorrhoeae in 2.
Multivariate analysis identified two factors associated with detectable HIV in semen: A current CD4 count between 554 and 735, compared with a lower count, cut the odds of HIV in semen 70% (odds ratio 0.3, 95% confidence interval [CI] 0.1 to 0.9, P = 0.027). And HIV DNA in PBMCs above versus below 318 copies per million cells tripled the odds (odds ratio 3.1, 95% CI 1.2 to 7.7, P = 0.015). HIV detection in semen was not associated with STIs, CDC stage, nadir or current CD4 count, duration of undetectable HIV in plasma, adherence to antiretroviral therapy, or number of sex partners.
The researchers noted that seminal HIV prevalence in this study was significantly higher than in a recent cross-sectional study of heterosexual French men (7.6% versus 3.1%, P = 0.016) [2]. Whether these levels of HIV in semen are infectious, they added, remains to be determined. "
1. There is viable HIV in the semen of many men who have "undetectable" viral loads.
2. How big a risk for infection this presents is unknown, but I'd be it's not zero.
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