[Viva] Fwd: CATIE News - Insight into HIV transmission risk when the viral load is undetectable and no condom is used
Denise Becker
dbecker106 at gmail.com
Thu Apr 10 11:05:37 PDT 2014
This is extremely good news.. the research of a very large group, showing
upper limits and lower limits of undetectable loads of women who are HIV
positive having condomless sex with their HIV negative partners: currently
between 0.028 and 0.
Denise
---------- Forwarded message ----------
From: CATIE <mailer at catie.ca>
Date: Thu, Apr 10, 2014 at 9:54 AM
Subject: CATIE News - Insight into HIV transmission risk when the viral
load is undetectable and no condom is used
To: dbecker106 at gmail.com
CATIE News - Bite-sized HIV and hepatitis C news bulletins
Insight into HIV transmission risk when the viral load is
undetectable and no condom is used
The sexual transmission of HIV occurs after an exposure to fluids that
contain HIV, such as semen and fluids from the vagina and rectum. The
amount of virus in these fluids (also known as viral load) is the most
important factor that determines whether an exposure to HIV will lead to
infection. Research shows that a higher viral load increases the risk of
HIV transmission and that a lower viral load decreases the risk.
The viral load in the *blood* of a person living with HIV is measured
regularly to monitor the success of antiretroviral therapy (also called
ART). Successful ART can reduce the viral load in the blood and other
bodily fluids to undetectable levels, which can reduce the risk of sexual
transmission. ART therefore represents an important new HIV prevention
tool, which also has the potential to reduce the guilt, blame and anxiety
associated with the possibility of transmitting HIV to a partner.
Gaps in the evidence
Several studies released over the past few years have confirmed that ART
has HIV prevention benefits. The most well-known study is the
randomized-controlled clinical trial known as HPTN 052. In this study,
early initiation of ART reduced the risk of HIV transmission by 96% among
heterosexual serodiscordant couples. However, the couples who participated
in this study reported having mostly vaginal sex, so the reduction in HIV
risk for anal sex remained unclear.
While HPTN 052 showed that ART can dramatically *reduce* the risk of HIV
transmission through vaginal sex, the *actual* risk of HIV transmission
(i.e., what the risk is lowered *to*) when the blood viral load is
undetectable remained unknown, particularly for condomless sex.
Fortunately, two ongoing studies are investigating these unanswered
questions. The studies are aiming to determine the *actual* risk of HIV
transmission (for condomless vaginal and anal sex) when the HIV-positive
partner's blood viral load is undetectable. Preliminary results from one of
these studies--the PARTNER Study--were released at the recent Conference on
Retroviruses and Opportunistic Infections (CROI) held in Boston in March
2014. These results are the first to provide direct evidence that ART can
reduce the risk of HIV transmission during anal sex.
The PARTNER study
The PARTNER study is a large observational study that is following
serodiscordant couples at over 70 HIV clinics in 14 European countries. All
of the couples enrolled:
- are either heterosexual or gay men
- consist of one HIV-negative partner and one HIV-positive partner who
is on ART
- do not use condoms regularly
The study began in September 2010 and is ongoing.
Once enrolled, the HIV-positive partner must commit to receiving their HIV
care from the study clinic and both partners are required to attend the
clinic every six months. At each visit, the HIV-positive partner's viral
load is measured, the HIV-negative partner's HIV status is checked, and
both partners are asked to complete a questionnaire about their sexual
behaviour in the past six months. The HIV-positive partner also receives
additional care, such as STI testing and information on the importance of
adherence to ART, and both partners are told about the importance of using
condoms to reduce the risk of HIV transmission.
If an HIV-negative partner becomes infected with HIV, a genetic analysis of
the virus is performed. This is done to confirm that the virus was
transmitted by the HIV-positive partner enrolled in the study and not by
someone else outside of the relationship.
Results
The preliminary results presented at CROI are part of a planned interim
analysis. They are based on information from couples, followed up until
November 2013, that met the following criteria:
- report of condomless sex
- an undetectable viral load in the HIV-positive partner (defined as
less than 200 copies per ml of blood)
- no use of PEP or PrEP by the HIV-negative partner
Of the 1,110 couples recruited by November 2013, 767 met the above
criteria. This included 282 same-sex male couples, 245 heterosexual couples
where the HIV-positive partner was female, and 240 heterosexual couples
where the HIV-positive partner was male. Overall, couples contributed a
total of 894 couple-years of follow-up (equivalent to following 894 couples
for a year).
At the start of the study, the HIV-positive partners had been on ART for an
average of 5 years and couples had been having condomless sex for an
average of 2 years.
During the preliminary study period, eligible couples reported condomless
sex an average of 45 times a year (approximately once a week). This ranged
from 16 times a year to 90 times a year. Same-sex male couples had sex more
often than heterosexual couples. Same-sex male couples were also more
likely to have a partner outside of the relationship (34% vs. 3% for
heterosexual couples) and have a sexually transmitted infection (16% vs.
5%).
Between September 2010 and November 2013, the couples reported more than
44,000 condomless sex acts. These included:
- 13,728 receptive vaginal sex acts (the HIV-negative partner receiving
the HIV-positive partner's penis into their vagina) with or without
ejaculation
- 14,295 insertive vaginal sex acts (the HIV-negative partner inserting
their penis into the HIV-positive partner's vagina)
- 7,738 receptive anal sex acts (the HIV-negative partner receiving the
HIV-positive partner's penis into their anus) with or without ejaculation
- 11,749 insertive anal sex acts (the HIV-negative partner inserting
their penis into the HIV-positive partner's anus)
Despite the large number of condomless sex acts, no HIV transmissions
occurred between any of the couples enrolled in the study. However, some of
the HIV-negative partners did become infected with HIV by a person outside
of the relationship.
Since there was no control group in the PARTNER trial, it is difficult to
know how many HIV transmissions would have occurred if the HIV-positive
partner was *not* on ART and did *not* have an undetectable viral load.
However, using information from previous studies, researchers estimated
that 15 HIV infections in heterosexual couples and 86 among same-sex male
couples would have occurred if the HIV-positive partner had *not *been on
ART.
The PARTNER study represents the first direct evidence that ART can reduce
the risk of HIV transmission for same-sex male couples.
Understanding and measuring certainty
The fact that no transmissions occurred in this study is very encouraging.
However, as with any research finding, it is important to consider the role
that chance may have played. This is particularly important when
investigating HIV transmission risk, because the average risk of HIV
infection can be relatively low in some cases, regardless of viral load.
The lower the risk, the more difficult it is to measure accurately. In
general, the larger the study, the more confident researchers can be that
the results are real and did not occur due to chance.
One way of measuring certainty is to use confidence limits. Confidence
limits take into account the potential effects of chance and suggest a
range of values that likely encompass the "true" risk. In the PARTNER
study, investigators calculated upper confidence limits for the risk of HIV
transmission per sex act and over time. The "upper confidence limit"
provides an estimate of the highest possible transmission risk that is
consistent with the study results.
For this study, upper confidence limits can be interpreted as follows:
- It is extremely *likely* that the "true" risk is somewhere between 0%
and the upper confidence limit.
- It is extremely *unlikely* that the "true" risk is *above* the upper
confidence limit.
The upper confidence limit is particularly important when a study finds
zero risk because it gives some indication of how close to zero the "true"
risk is likely to be.
Risk per-act of sex
Upper confidence limits were calculated for the risk of HIV transmission
per act of condomless sex with an HIV-positive partner:
- Receptive vaginal sex (with or without ejaculation) - 0.028%
- Insertive vaginal sex - 0.027%
- Receptive anal sex (with or without ejaculation) - 0.05%
- Insertive anal sex - 0.033%
For example, the upper confidence limit for *receptive anal sex* can be
interpreted as follows:
Given the number of *receptive anal sex* acts that occurred and the fact
that no HIV infections were observed, it is extremely *likely* that the
"true" risk is somewhere between 0% and 0.05%, and extremely
*unlikely*that it is above 0.05%. Although it is still possible that
the "true" risk
is zero, or only slightly higher than zero, the researchers could not rule
out the possibility that the risk is as high as 0.05%.
Despite this uncertainty, this research is still meaningful. Many of the
upper confidence limits are lower than the HIV transmission risks that have
been estimated for when a person's viral load is *detectable*. For example,
the average per-act transmission risk for receptive anal sex has been
estimated to be 1.4% when the viral load is *detectable*. However, the
PARTNER study found that this risk is extremely likely to be below 0.05%
when the viral load is *undetectable*.
Previous studies have estimated the average risk per condomless sex act
when the viral load is *detectable* to be 0.08% for receptive vaginal sex,
0.04% for insertive vaginal sex and 0.06-0.62% for insertive anal sex.
Therefore the PARTNER study strongly suggests that ART reduced the risk of
HIV transmission for all types of sex.
Risk over time
Upper confidence limits were also calculated for a couple's 10-year risk of
HIV transmission when the HIV-positive partner has an undetectable viral
load:
- Receptive vaginal sex (with or without ejaculation) - 11.7%
- Insertive vaginal sex - 11.4%
- Receptive anal sex (with or without ejaculation) - 17.9%
- Insertive anal sex - 12.8%
For example, the upper confidence limit for *receptive anal sex* can be
interpreted as follows:
Given that couples were having condomless sex about once a week, it is
extremely likely that the 10-year risk of HIV transmission is somewhere
between 0 and 17.9% for *receptive anal sex*. While it is still possible
that the "true" risk is zero, or only slightly higher than zero, the study
could not rule out the possibility that the risk is as high as 17.9%.
It is important to note that the size of the upper confidence limit
reflects the effects of chance. Receptive anal sex has the highest upper
confidence limits because there were fewer receptive anal sex acts during
the study compared to other types of sex. The lower number of sex acts
means chance may have played a greater role.
Conclusion
The preliminary results from the PARTNER study provide important and
encouraging new insight into the risk of transmitting HIV sexually when a
person's viral load is undetectable and no condom is used. These results
can help serodiscordant couples assess their HIV risk and make informed
decisions.
The investigators of the PARTNER study concluded that the overall risk of
HIV transmission through condomless sex for couples in stable
serodiscordant relationships (when the HIV-positive partner is on ART,
receives regular HIV care, and has an undetectable blood viral load) is
"extremely low, but uncertainty over the risk remains, particularly over
receptive anal sex. Additional follow-up in MSM (men who have sex with men)
is essential to provide more precise estimates for transmission risk given
the current assumptions of safety in some communities."
As the PARTNER study continues to follow couples who continue to have sex,
the upper confidence limits will become "tighter" and move closer to
zero--assuming that no HIV transmissions occur. This will allow the
investigators to more confidently conclude that the risk of HIV
transmission is "extremely low" for all types of vaginal and anal sex. The
PARTNER study will continue to follow heterosexual couples until April
2014. Same-sex male couples will be followed until 2017 and the
investigators plan to enroll 450 more gay male couples.
--*James Wilton*
*Resources*
Official Q&A for PARTNER
Studies<http://www.chip.dk/portals/0/files/CROI_2014_PARTNER_QA.pdf>
HPTN 052: The trial that changed
everything<http://www.catie.ca/en/treatmentupdate/treatmentupdate-185/prevention/htpn-052-trial-changed-everything>-
*TreatmentUpdate*
Undetectable viral load and HIV transmission risk: results of a systematic
review<http://www.catie.ca/en/catienews/2013-03-07/undetectable-blood-viral-load-and-hiv-transmission-risk-results-systematic-revi>-
*CATIE
News*
Treatment and viral load: what do we know about their effect on HIV
transmission?<http://www.catie.ca/en/pif/fall-2013/treatment-viral-load-and-hiv-transmission>-
*Prevention
in Focus*.
Putting a number on it: the risk from an exposure to
HIV<http://www.catie.ca/en/pif/summer-2012/putting-number-it-risk-exposure-hiv>-
*Prevention
in Focus*
*References*
1. Baeten JM, Kahle E, Lingappa JR et al. Genital HIV-1 RNA predicts
risk of heterosexual HIV-1 transmission. *Science Translational Medicine*.
2011 Apr 6;3(77):77ra29.
2. Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection
with early antiretroviral therapy. *New England Journal of Medicine*.
2011 Aug 11;365(6):493-505.
3. Loutfy MR, Wu W, Letchumanan M et al. Systematic review of HIV
transmission between heterosexual serodiscordant couples where the
HIV-positive partner is fully suppressed on antiretroviral therapy. *PLoS
One*. 2013;8(2):e55747.
4. Rodger A et al. *HIV transmission risk through condomless sex if HIV+
partner on suppressive ART: PARTNER study. *In: Program and abstracts of
the 21st Conference on Retroviruses and Opportunistic Infections, March 3
to 6th, 2014, Boston, U.S., abstract 153LB.
5. Baggaley RF, White RG, Boily M-C. HIV transmission risk through anal
intercourse: systematic review, meta-analysis and implications for HIV
prevention. *International Journal of Epidemiology*. 2010
Aug;39(4):1048-63.
6. Boily M-C, Baggaley RF, Wang L et al. Heterosexual risk of HIV-1
infection per sexual act: systematic review and meta-analysis of
observational studies. *Lancet Infectious Diseases*. 2009
Feb;9(2):118-29.
7. Jin F, Jansson J, Law M et al. Per-contact probability of HIV
transmission in homosexual men in Sydney in the era of HAART. *AIDS*.
2010 Mar 27;24(6):907-13.
8. Wilson DP, Law MG, Grulich AE et al. Relation between HIV viral load
and infectiousness: a model-based analysis. *Lancet*. 2008 Jul
26;372(9635):314-20.
9. Wilson DP, Law MG, Gruclich AE et al. HIV transmission under highly
active antiretroviral therapy. *Lancet*. 2008 Nov 22;372(9652):1807.
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www.denise-becker.com
Queen's Gold Jubilee Medal
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cell: 778-903-5106
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