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Antiretroviral therapy treatment for HIV-positive people

NIHR Signal Antiretroviral treatment can reduce the risk of HIV transmission between male partners to ‘zero’

Published on 27 June 2019

doi: 10.3310/signal-000785

The risk of transmission of HIV between gay couples when the HIV-positive partner is taking antiretroviral treatment that successfully suppresses the viral load is ‘effectively zero.’

A study of men from 14 European countries, including the UK, found no cases of transmission of HIV from an HIV-positive partner taking antiretroviral therapy to an HIV-negative partner, as long as the viral load of the HIV-positive partner remained undetectable or very low.

The study recorded an average of two years during which the partners reported condomless anal sex. Although there were 15 cases where men who were initially HIV-negative became infected with HIV, viral genetic testing showed that in no case was this transmission from the partner taking antiretroviral therapy.

The researchers emphasised that adherence to treatment, regular testing of viral load and of HIV status are important to ensure HIV transmission does not occur.

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Why was this study needed?

Without the suppression of HIV through antiretroviral therapy, the virus can be transmitted through blood and semen during sexual activity. While condoms reduce the risk of infection, they are not always used consistently, and people are not always in a position to insist on their use.

Previous studies have already found that the rate of transmission of HIV between partners where one was HIV-negative and the other was HIV-positive was very low - if the viral load was suppressed to undetectable levels in the HIV-positive partner. However, these earlier studies had included mostly heterosexual couples, and this research sought to clarify if the same applied for men who have sex with men.

This study was an extension to a previous mixed study of 340 male couples and 548 heterosexual couples. It recruited additional male couples, to provide more precise estimates of the risk of HIV transmission between partners in gay relationships.

What did this study do?

PARTNER2 was an observational study. Researchers recruited 972 male couples aged 18 or over where:

  • one partner was HIV-positive and one HIV-negative,
  • the HIV-positive partner was taking antiretroviral therapy and expected to continue,
  • the couple reported having condomless penetrative sex in the month before enrolment and were expected to continue.

The antiretroviral regime, CD4 count and HIV-1 RNA load were recorded for HIV-positive partners at each visit, while the HIV-negative partners were tested for HIV every 6 to 12 months.

Questionnaires every 4 to 6 months recorded adherence to antiretroviral therapy, sexual behaviour, other sexually transmitted infections, use of pre- or post-exposure prophylaxis and injecting drug use.

This was a well-conducted study in a large number of men so the results should be reliable.

What did it find?

  • From the 972 couples recruited, 782 couples contributed 1,593 couple-years of follow-up, with an average of two years of follow-up per couple. In 96% of the couple-years available, the HIV-positive partner had an undetectable viral load (less than 50 copies/ml plasma HIV-1 RNA), and in the remaining 4%, viral load was very low (between 50 and 200 copies/ml).
  • The median frequency for couples having condomless sex during the study was 43 times a year. There were no within-couple HIV transmissions recorded. The estimated transmission rate was 0.0 (upper limit of 95% confidence interval (CI) 0.23). This was equivalent to one transmission per 435 years of condomless sex. Without antiretroviral therapy, based on previous figures, the researchers say they would have expected to see around 472 HIV transmissions (95% CI 83 to 714).
  • Although 15 men initially HIV-negative did become HIV-positive during the study, RNA sequencing showed the virus had not been transmitted by the partner taking virally suppressive antiretroviral therapy. Condomless sex with other partners was reported by 37% of the HIV-negative men.
  • Only eight couple-years of follow-up were recorded during the first six months of antiretroviral therapy for the HIV-positive partner. So we can’t be sure that the results apply to men in the early months of antiretroviral therapy, when viral load may not yet be fully suppressed. Most couples reported having condomless sex for a median one year before being enrolled in the study.
  • Sexually transmitted infections were common, occurring in 24% of HIV-negative men and 27% of HIV-positive men. Condomless sex was reported 6,090 times while an infection was present.

What does current guidance say on this issue?

The NICE clinical knowledge summary for treatment of people with established HIV infection states: “Advise using condoms with water-based lubricant for vaginal and anal sex, and condoms or dams (latex sheets) for oral sex.”

The summary, last revised in 2018 and due to be updated in 2020, does not touch on transmission risk between partners when viral load is suppressed.

What are the implications?

The study demonstrates that HIV treatment can reduce viral load to levels where the risk of transmission is very low to non-existent.

As such, it shows the importance to their partners of HIV testing and treatment for people at risk of HIV, and of good adherence to antiretroviral treatment and regular testing of viral load for people who are HIV-positive. The same benefits would not be seen in practice if adherence to treatment were not as good as in the men in this study

It does also highlight the high risk of other sexually transmitted infections when condoms are not used.

Citation and Funding

A Rodger, V Cambiano, T Bruun et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. 2019; May 2. doi: 10.1016/S0140-6736(19)30418-0. [Epub ahead of print].

This project was funded by the NIHR Research for Patient Benefit Programme (project number PB-PG-1013-32069).

Bibliography

Cohen M S. Successful treatment of HIV eliminates sexual transmission. Lancet. 2019: May 2. doi: 10.1016/S0140-6736(19)30701-9. [Epub ahead of print].

NICE. HIV infection and AIDS. Scenario: established HIV infection. Clinical Knowledge Summary. London: National Institute for Health and Care Excellence; last updated 2018.

Why was this study needed?

Without the suppression of HIV through antiretroviral therapy, the virus can be transmitted through blood and semen during sexual activity. While condoms reduce the risk of infection, they are not always used consistently, and people are not always in a position to insist on their use.

Previous studies have already found that the rate of transmission of HIV between partners where one was HIV-negative and the other was HIV-positive was very low - if the viral load was suppressed to undetectable levels in the HIV-positive partner. However, these earlier studies had included mostly heterosexual couples, and this research sought to clarify if the same applied for men who have sex with men.

This study was an extension to a previous mixed study of 340 male couples and 548 heterosexual couples. It recruited additional male couples, to provide more precise estimates of the risk of HIV transmission between partners in gay relationships.

What did this study do?

PARTNER2 was an observational study. Researchers recruited 972 male couples aged 18 or over where:

  • one partner was HIV-positive and one HIV-negative,
  • the HIV-positive partner was taking antiretroviral therapy and expected to continue,
  • the couple reported having condomless penetrative sex in the month before enrolment and were expected to continue.

The antiretroviral regime, CD4 count and HIV-1 RNA load were recorded for HIV-positive partners at each visit, while the HIV-negative partners were tested for HIV every 6 to 12 months.

Questionnaires every 4 to 6 months recorded adherence to antiretroviral therapy, sexual behaviour, other sexually transmitted infections, use of pre- or post-exposure prophylaxis and injecting drug use.

This was a well-conducted study in a large number of men so the results should be reliable.

What did it find?

  • From the 972 couples recruited, 782 couples contributed 1,593 couple-years of follow-up, with an average of two years of follow-up per couple. In 96% of the couple-years available, the HIV-positive partner had an undetectable viral load (less than 50 copies/ml plasma HIV-1 RNA), and in the remaining 4%, viral load was very low (between 50 and 200 copies/ml).
  • The median frequency for couples having condomless sex during the study was 43 times a year. There were no within-couple HIV transmissions recorded. The estimated transmission rate was 0.0 (upper limit of 95% confidence interval (CI) 0.23). This was equivalent to one transmission per 435 years of condomless sex. Without antiretroviral therapy, based on previous figures, the researchers say they would have expected to see around 472 HIV transmissions (95% CI 83 to 714).
  • Although 15 men initially HIV-negative did become HIV-positive during the study, RNA sequencing showed the virus had not been transmitted by the partner taking virally suppressive antiretroviral therapy. Condomless sex with other partners was reported by 37% of the HIV-negative men.
  • Only eight couple-years of follow-up were recorded during the first six months of antiretroviral therapy for the HIV-positive partner. So we can’t be sure that the results apply to men in the early months of antiretroviral therapy, when viral load may not yet be fully suppressed. Most couples reported having condomless sex for a median one year before being enrolled in the study.
  • Sexually transmitted infections were common, occurring in 24% of HIV-negative men and 27% of HIV-positive men. Condomless sex was reported 6,090 times while an infection was present.

What does current guidance say on this issue?

The NICE clinical knowledge summary for treatment of people with established HIV infection states: “Advise using condoms with water-based lubricant for vaginal and anal sex, and condoms or dams (latex sheets) for oral sex.”

The summary, last revised in 2018 and due to be updated in 2020, does not touch on transmission risk between partners when viral load is suppressed.

What are the implications?

The study demonstrates that HIV treatment can reduce viral load to levels where the risk of transmission is very low to non-existent.

As such, it shows the importance to their partners of HIV testing and treatment for people at risk of HIV, and of good adherence to antiretroviral treatment and regular testing of viral load for people who are HIV-positive. The same benefits would not be seen in practice if adherence to treatment were not as good as in the men in this study

It does also highlight the high risk of other sexually transmitted infections when condoms are not used.

Citation and Funding

A Rodger, V Cambiano, T Bruun et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. 2019; May 2. doi: 10.1016/S0140-6736(19)30418-0. [Epub ahead of print].

This project was funded by the NIHR Research for Patient Benefit Programme (project number PB-PG-1013-32069).

Bibliography

Cohen M S. Successful treatment of HIV eliminates sexual transmission. Lancet. 2019: May 2. doi: 10.1016/S0140-6736(19)30701-9. [Epub ahead of print].

NICE. HIV infection and AIDS. Scenario: established HIV infection. Clinical Knowledge Summary. London: National Institute for Health and Care Excellence; last updated 2018.

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study

Published on 2 May 2019

A Rodger, V Cambiano, T Bruun, P Vernazza, S Collins, O Degen, G Corbelli, V Estrada, A Geretti, A Beloukas, D Raben, P Coll, A Antinori, N Nwokolo, A Rieger, J Prins, A Blaxhult, R Weber, A Van Eeden, N Brockmeyer, A Clarke, J del Romero Guerrero Guerrero, F Raffi, J Bogner, G Wandeler, J Gerstoft, F Gutiérrez, K Brinkman, M Kitchen, L Ostergaard, A Leon, M Ristola, H Jessen, H Stellbrink, A Phillips, J Lundgren

The Lancet , 2019

Background The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. Methods The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. Findings Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). Interpretation Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. Funding National Institute for Health Research.

Expert commentary

It has increasingly been recognised that reducing the amount of HIV in the blood using anti-retroviral drugs reduces the chances of HIV being passed on during sex.

By evaluating this in a large number of couples, the PARTNER2 study provides an accurate estimate of the risk of transmitting infection in HIV-positive gay men who are taking effective therapy. The study confirms that the risk to their HIV-negative partners in this situation is essentially zero.

This means that an HIV-negative gay man does not need to take HIV medication either before or after sex to prevent catching infection (also known as pre- or post-exposure prophylaxis) when having sex with a partner who is on effective HIV treatment.

Professor Jonathan Ross, Professor of Sexual Health and HIV, University Hospitals Birmingham NHS Foundation Trust

The commentator declares personal fees from GSK Pharma and Janssen Pharma, and ownership of shares in GSK Pharma. He is an officer and charity trustee for the British Association for Sexual Health and HIV (BASHH) and the International Union against Sexually Transmitted Infections (IUSTI), and a charity trustee for the Sexually Transmitted Infections Research Foundation.