5.8. Zero HIV transmission cases: PARTNER1 and PARTNER2 studies
HIV infection is no longer the "plague of the 21st century". This is a chronic manageable condition, just like many others, that can be treated effectively and with which you can have a normal quality life. With HIV, you can have a relationship, have children, run marathons and have a dizzying career, grow old and retire - just like you would without HIV. All this is due to new scientific data, which confirmed that having an undetectable viral load makes sexual transmission of HIV impossible. And this, in turn, is achievable with effective antiretroviral therapy.
Now, the proof of the "U U" principle transmission of HIV. ("Undetectable equals untransmittable") is based on two large-scale international studies PARTNERI and PARTNER2. The first was conducted mainly with heterosexual, and the second with homosexual serodiscordant couples. Both studies were conducted in 75 centers in 14 European countries. During the entire observation period, in PARTNERI, 58.000 sexual acts were recorded without using a condom, and in PARTNER2 - 77.000 times of sex without a condom. In both studies, PARTNER 1 and 2, there was not a single case of sexual transmission of HIV in serodiscordant couples, when the HIV positive partner had a stable undetectable viral load. Thus, studies confirm the effectiveness of the "treatment as prevention" approach to prevent the sexual transmission of HIV.
PARTNER1
From 2010 to 2014, 1,166 couples were recruited to participate in the PARTNER1 study. Of these, 1004 couples visited the doctor at least once, and 888 couples (548 heterosexual and 340 MSM - men who have sex with men) were already directly involved in the observation. All these pairs were serodiscordant, i.e. one partner was HIV positive and the other was HIV negative. The main criteria for participation in PARTNER1 was that the HIV-positive partner had an undetectable viral load of less than 200 copies / ml and the practice of unprotected sex with his partner. The main reasons for excluding couples from observation were not providing an HIV test to a negative partner, using post-exposure or pre-exposure prophylaxis during the study, having sex only with a condom, the concentration of HIV-1 RNA in plasma is more than 200 copies / ml, and the inaccessibility of plasma measurement of one of partners. The average age of participants was 40 years. For all the time of observation, homosexual couples had sex without a condom on average 1.5 years (interquartile range * from 0.5 to 3.5 years), heterosexual couples in whom a woman was HIV-positive were 2.8 years old (MCDD from 0.6 to 7.5 years), and 3.6 years - where a man (MKD from 0.7 to 11.4 years). Thus, 25% of homosexual couples had sex without a condom for less than 6 months. Similarly, 25% of heterosexual couples where a man was HIV positive have been practicing sex without a condom for more than 11 years.
The residence time of an HIV-positive partner for antiretroviral therapy (ART) was considered important, because the longer someone is treated, the lower the likelihood of viral load. In addition, the longer someone had an undetectable viral load, the lower the risk of virologic rebound after the suppression of viral load. In the MSM group, the HIV-positive partner took ARVT for an average of 4.8 years (MKD from 1.9 to 11.4 years), in heterosexual couples in which the woman was HIV-positive — 7.5 years (MKD from 3, 3 to 14.2 years), and in which HIV-positive was a man - 10.6 years (MKD from 4.3 to 15.6 years).
During the entire observation period, 58,000 sexual acts were recorded without using a condom. The main result of the study was that there was not a single transmission of HIV from an HIV-positive to an HIV-negative partner in a couple. Other STIs recorded at the time of observation did not affect the result, nor did the probable viral jumps between viral load tests.
Approximately 33% of homosexual and 4% of heterosexual couples were in open relationships - had sex with other partners. In such cases, they did not always know about HIV status and possible viral load of the partner. Therefore, during the study, 11 HIV-negative partners became HIV-positive (10 MSM, 1 heterosexual partner; 8 of them reported unprotected sex with other partners). No phylogenetic related transmissions were recorded, i.e. none of these transmissions was associated with their HIV-positive partner, which was with undetectable viral load.
The main reasons why HIV-negative condom partners refused during the study were the belief that the risk of HIV transmission was very low (57% of heterosexual men, 52% of heterosexual women, 63% of MSM), and that sex was more pleasant without a condom (38 % of heterosexual men, 41% of heterosexual women, 61% of MSM). 15% of HIV-negative women reported not using a condom because they were trying to get pregnant.
Among sexual acts, anal sex with ejaculation is one of the most risky compared to others. In the PARTNER1 study, 38.3% of MSM practiced only anal sex. among heterosexual couples, they were engaged in 11.1%. Thus, this study was aimed primarily at heterosexual vaginal sexual contact. To provide more accurate estimates of the risk of HIV transmission in MSM through anal sex in the context of ART, additional monitoring was conducted in this group - PARTNER2.
PARTNER2
For the PARTNER2 study, 972 msd pairs from 14 European countries were recruited. The study included 783 couples (the exclusion from the study was based on the same parameters as in PARTNER1). all participants reported cases of sexual contact when an HIV-negative partner did not take pre-exposure prophylaxis or was not protected while the HIV-positive partner had an undetectable viral load of <200 copies / ml. The average age was 43 years (MKD from 31 to 46 years) and couples have already had sex without a condom for an average of one year (MKD from 0.4 to 2.9 years). HIV-positive partners had been on ART for an average of 4 years (MCD from 2 to 9 years), with high adherence (98% of participants took more than 90% of medicines), and 93% independently reported the presence of undetectable viral load.
The average observation time was 1.6 years (MKD from 0.9 to 2.9 years), when couples had sex without a condom about once a week. On average, couples had 43 unprotected intercourse per year (MKD from 19 to 74). For the entire time of the study, 77,000 sexual contacts were recorded without the use of condoms.
Many couples were in open relationships: 37% of HIV-negative partners reported having other sexual partners outside their relationship. During follow-up, 24% of negative and 27% of positive partners reported at least one STI other than HIV.
For a total of eight years of follow-up, 15 HIV-negative partners became HIV-positive, of which 10 MSM were recorded in PARTNER1. It is important to note that all new HIV infections were not associated with an HIV-positive partner who had an undetectable viral load.
In both PARTNER1 and PARTNER2, not a single case of sexual transmission of HIV was observed in serodiscordant couples, when the HIV-positive partner had a stable undetectable viral load.
An important aspect of both studies was the quantitative analysis of possible risk. Thus, even when HIV transmission was not observed and was zero, it is mathematically possible to calculate the upper risk range, which may be possible, given that the data are always limited. This is the 95% confidence interval ** (95% CI).
The initial PARTNER1 study calculated the top 95% CI as 0.46 / 100 years in general, which is equivalent, at worst, to the condition that a couple should have sex for about 200 years for HIV transmission. This is the highest level. In fact, it will most likely take thousands of years. Since two thirds of the participants were heterosexual, this figure was higher for MSM at 0.84 / 100 years. But the new results of PARTNER2 reduce the risk level with 95% CI to 0.23 / 100 years in homosexual couples: this is equivalent in the worst case to the condition when the couple has to have sex for 400 years so that it can be transmitted by HIV.
All these results suggest that HIV is not sexually transmitted with an undetectable viral load.
* Interquartile range (MQD) is the range between the 25th and 75th percentiles. It includes the central 50% of observations, where 25% of observations are below the central point and 25% above.
** Confidence interval (CI) is the interval of values around the estimate, where the “true” (unknown) population mean is found with a given level of confidence. For example, if you repeat one experiment several times, the interval will contain the true average of the population in 95% of cases.
[I] Thomas C. Quinnet al. Viral Load and Heterosexual Transmission of Human Immunodeficiency Virus Type 1. N Engl J Med. 2000; 342:921-929
[2] Alison J. Rodger et al. sexual Activity Without condoms and Risk of HIV Transmission in serodifferent couples when the HIV-Positive Partner IS Using suppressive Antiretroviral Therapy. JAMA. 2016; 316(2):171-181
[3] Alison Rodger et al. HIV transmission risk throughcondomless sex in gay couples withsuppressive ART: The PARTNER2 studyextended results in gay men. The 22nd AIDS International conference on HIV science, Amsterdam The Netherlands 23-27 July 2018.