Contagiousness in treated HIV-1 infection

Abstract

Background

Effective antiretroviral treatment of HIV-1, defined as continuously undetectable virus in blood, has substantial effects on the infectiousness and spread of HIV.

Aim

This paper outlines the assessment of the Swedish Reference Group for Antiviral Therapy (RAV) and Public Health Agency of Sweden regarding contagiousness of HIV-infected persons on antiretroviral therapy (ART).

Results and Conclusion: The expert group concludes that there is no risk of transmission of HIV during vaginal or anal intercourse if the HIV-infected person fulfils the criteria for effective ART.

Summary: The effective antiretroviral therapy (ART) for HIV-1 infection has dramatically reduced the morbidity and mortality among people who live with HIV. ART also has a noticeable effect on the infectiousness and on the spread of the disease in society. Knowledge about this has grown gradually.

For ART to be regarded effective, the level of the HIV RNA in the plasma should be repeatedly and continuously undetectable and the patient should be assessed as continually having high adherence to treatment.

Based on available knowledge the Swedish Reference Group for Antiviral Therapy (RAV) and the Public Health Agency of Sweden make the following assessment:

• There is no risk of HIV transmission during vaginal or anal intercourse if the HIV positive person fulfils the criteria for effective treatment. This includes intercourse where a condom is not used. However, there are a number of other reasons for recommending the use of condoms, primarily to protect against the transmission of other STIs (sexually transmitted infections) and hepatitis, as well as unwanted pregnancy. The occurrence of other STIs does not affect the risk of HIV transmission in persons on effective ART.

• It is plausible that the risk for transmission of HIV infection between people who inject drugs and share injection equipment is reduced if the individual with HIV is on effective ART, but there are no studies that directly show this.

• The risk of transmission from mother to child during pregnancy, labour and delivery is very low if the mother’s treatment is initiated well before delivery and if the treatment aim of undetectable virus levels is attained. This is dependent on healthcare services being aware of the mother’s HIV infection at an early stage.

• In most contacts with health and medical care, including dental care, the risk of transmission is not significant if the patient is on effective treatment, but the risk may remain, although considerably reduced, in more advanced interventions such as surgery. When an incident with risk of transmission occurs, the patient must always inform those potentially exposed about his or her HIV infection.

Keywords:

• HIV
• contagiousness
• antiretroviral therapy
• transmission

Background

Knowledge about how antiretroviral treatment (ART) reduces the contagiousness of people living with HIV (PLHIV) has gradually increased. Already in 2008, the Swiss National AIDS Commission stated that PLHIV on effective ART under certain conditions should not be considered contagious in sexual contacts [1]. In 2011, the HPTN 052 study showed that early antiretroviral therapy (in this document, ART means treatment for HIV-1) significantly reduced the risk of infection through sexual contacts [2]. Against this background the Public Health Agency of Sweden together with the Swedish Reference Group for Antiviral Therapy (RAV), in 2013, published a position statement on risk of HIV transmission from patients on antiretroviral therapy [3]. Since then, several key studies have been conducted, justifying a revision of the position statement and its conclusions.

The most important studies that have added to the evidence are the so-called Opposites Attract, PARTNER1 and PARTNER2 studies, which are summarised briefly below. All of these studies include serodiscordant couples of MSM (men who have sex with men) as well as heterosexual couples [4–6]. Serodiscordant is defined as one partner in the couple having HIV antibodies in blood or HIV RNA without antibodies, i.e. carrying HIV, while the other partner does not, at the start of study. The studies focus on sexual intercourse where the partner with HIV has effective ART and where no condom or other pre- or post-exposure prophylaxis has been used (see definition of effective ART below). In total, more than 125,000 such episodes have been followed up and no case of transmission from the partner with HIV has been detected.

The Opposites Attract study was conducted at 13 clinics in Australia, one clinic in Brazil and one clinic in Thailand from May 2012 to March 2016 [4]. The study included 343 MSM couples, of which 253 provided data on risk of transmission in unprotected sex, i.e. anal intercourse where neither condom nor pre-exposure prophylaxis was used. Effective treatment was defined as a viral load of up to 200 copies/mL blood plasma. The viral load of the partner with HIV infection was monitored according to normal clinical routine at intervals of 3–6 months. The study recorded 16,800 episodes of unprotected sexual intercourse. Three cases of HIV infection in the previously uninfected partner were recorded during the follow-up period, but phylogenetic typing of virus showed that none of these infections could be attributed to the partner with HIV. Thus, the point estimate for the risk of transmission was zero, while the upper limit of the 95% confidence interval was 0.63 cases per 100 years. In 1.9 percent of the episodes of unprotected anal intercourse (239/16,800 episodes), the partner with HIV infection had detectable virus above 200 copies/mL and in the majority of these (219 intercourse) the viral load was above 1,000 copies/mL. Despite this, no transmission of HIV was detected. Other sexually transmitted infections (STIs) were relatively common and were diagnosed in one-third of HIV-positive partners and one-quarter of HIV-negative partners.

The PARTNER1 study was conducted at 75 clinics in 14 European countries, including Sweden, from May 2010 to March 2014 [5]. The study included 1,166 heterosexual couples and MSM couples, of which 888 couples (548 heterosexuals and 340 MSM) contributed data on transmission risk in unprotected intercourse where neither condom nor pre-exposure prophylaxis was used. Effective ART was defined as a viral load of up to 200 copies/mL. The viral load of the partner with HIV infection was monitored according to normal clinical routine at intervals of 6–12 months. The study recorded approximately 58,000 episodes of unprotected intercourse (36,000 heterosexual and 22,000 MSM). Eleven cases of HIV infection in the previously uninfected partner were recorded, but phylogenetic typing of the virus showed that none of these infections were from the regular HIV infected partner. Thus, the point estimate for the infection risk was zero, while the upper limit of the 95% confidence interval was 0.30 cases per 100 years. During six percent of the follow-up period, the viral load was 50–200 copies/mL. Other STIs were relatively common and were diagnosed in 17–18 percent of MSM participants and six percent of heterosexual participants.

In the PARTNER2 study, which was a continuation of the PARTNER1 study, only MSM couples were studied from May 2010 to April 2018 [6]. Thus, data on risk of transmission in MSM couples overlap between the two studies. The study included 972 MSM couples, of which 779 couples contributed data on transmission risk in unprotected anal intercourse. The definition of effective ART and the intervals for virus control were the same as for the PARTNER1 study. A total of 74,567 episodes of unprotected anal intercourse was recorded. Seventeen cases of HIV infection in the previously uninfected partner were recorded, but none of these infections originated from the permanent partner. Thus, the point estimate for the infection risk was zero in this study as well, while the upper limit of the 95% confidence interval was 0.24 cases per 100 years. During four percent of the follow-up time, the viral load was above 50–200 copies/mL. Other STIs were relatively common and were diagnosed in 24 percent of HIV-negative men and 27 percent of men with HIV infection during the follow-up period.

The findings in these and previous studies have led to a comprehensive scientific discussion regarding how ART could be used as prevention against HIV spread (treatment-as-prevention, TasP). Based on these finding, statements from several national expert groups have been published, including in the UK through The British HIV Association (BHIVA) and the Expert Advisory Group on AIDS (EAGA), who have stated that the risk of transmission of HIV in sexual contacts is extremely low from people with effective ART [7].

The practice of post-exposure prophylaxis is well-established in many countries. In recent years, a number of countries including Sweden [8–10], also recommend pre-exposure prophylaxis, i.e. treatment with antiretroviral drugs for the prevention of HIV in persons with an ongoing or recurrent significant risk of contracting HIV, especially in the MSM group.

Data from the Swedish national quality of care register InfCareHIV, which covers >99% of all PLHIV in Sweden, show that at the beginning of 2019, 98.5% of all PLHIV in Sweden received ART. Of these, 96.5% had a viral load of less than 50 HIV RNA copies/mL plasma. Considering this and the results of the above-mentioned studies, there is a continued great need to disseminate information regarding the current risk of transmission of HIV from Swedish patients who are on effective ART.

Through InfCareHIV and the reporting through the national surveillance system SmiNet, Sweden has very good opportunities to monitor the epidemiological development and treatment results of PLHIV. In this way, the knowledge base can be continuously updated and evaluated regarding the infection transmission and epidemiology as well as the medical situation of PLHIV.

Medical consequences of HIV infection

• HIV infection is still a serious and incurable infectious disease that requires lifelong treatment and regular contact with health care.

• The life expectancy of people living with HIV in countries with access to effective treatment has increased significantly and is approaching that of comparable uninfected persons.

• In Sweden, HIV infection nowadays very rarely leads to death if the infection is diagnosed early and ART can be started before severe immunodeficiency has developed.

Modern antiretroviral combination therapy was introduced in 1996 and quickly led to a dramatic reduction in both morbidity and mortality caused by HIV infection. Since then, there have been further improvements in both antiretroviral efficacy and reduction of side effects. This has led to improved patient experiences of antiretroviral therapy and health-related quality of life [11,12].

HIV treatment outcomes in Sweden are very good and among the best in the world. Several studies show that the life expectancy of PLHIV in countries with access to effective treatment is increasing and is now approaching that of the rest of the population [13–15]. An important reason for the still slightly shorter life expectancy is, in addition to lifestyle factors and socioeconomic status, deaths occurring in patients diagnosed at very late stage of HIV infection when it is too late to start antiretroviral therapy or too late for the treatment to have sufficient effect [16]. Data from the national quality register InfCareHIV show that all-cause mortality among PLHIV in Sweden today is lower than one percent annually. However, among people diagnosed at a late stage with severely affected immune systems or AIDS, or those who have been infected through intravenous drug use, mortality rates are significantly higher.

Definition of effective treatment

For an antiretroviral HIV treatment to be considered effective, the following criteria must be met according to Swedish expert consensus:

• HIV viral load (HIV RNA) in blood plasma should be continuously undetectable and verified through at least two consecutive viral load measurements with a 3- to 6-month interval.

• The patient should be assessed as having continuously good treatment adherence.

• Follow-up of viral load and adherence to treatment should be performed regularly in accordance with RAV HIV treatment guidelines [10].

Undetectable viral load is defined as viral load below the lower limit of detection with the tests used in Swedish routine care, i.e. <20 or <50 HIV RNA copies/mL plasma depending on test used. In a small proportion of patients with good adherence and effective treatment, low, but measurable viral load is seen; up to 200 copies/mL. When viral load is occasionally detected up to this level, it is called “blips”. Patients with blips of up to 200 copies/mL are still considered to have effective treatment.

In the PARTNER and Opposites Attract studies, the effective treatment was defined as a viral load of <200 copies/mL. As the number of study participants with viral loads in the range of 50–200 copies/mL was low in these studies, it is not possible to scientifically determine that infectiousness is minimal or zero in this range. However, no cases of HIV transmission have been reported in the scientific literature for patients with viral loads in this interval.

In our statement from 2013, the criterion for effective treatment stated that there should be no clinical or epidemiological suspicion of another ongoing STI, as this theoretically could increase the risk of HIV transmission, despite effective ART. In Opposites Attract and PARTNER studies, STI was not uncommon, but nevertheless no transmission of HIV was observed. Thus, available data unequivocally suggest that the presence of another STI does not affect the risk of HIV transmission in persons on effective ART. Therefore, co-infection with another STI does not change the patient’s status as having effective ART.

Risk of transmission in vaginal and anal intercourse with effective ART

• There is no risk of transmission of HIV during vaginal and anal intercourse if the partner with HIV infection meets the criteria for effective ART.

• The above applies to each individual sexual contact and to repeated contacts over a long period (years) and regardless of whether the person with HIV infection is penetrating or receptive in the sexual act.

The above assessment is based primarily on the results of the three studies; Opposites Attract, PARTNER1 and PARTNER2 [4–6]. As described in previous sections, these studies included serodiscordant MSM and heterosexual couples. The partner with diagnosed HIV infection was on virally suppressive ART at baseline (<200 HIV RNA copies/mL plasma). In total, more than 125,000 condomless vaginal and anal intercourses were documented without other pre- or post-exposure prophylaxis. There were no cases of transmission of infection from the partner with HIV to the uninfected partner. The above assessment of the risk of infection during sexual intercourse also applies to oral sexual contacts. There are no studies that have directly studied the risk of infection in oral sexual contacts when the person with HIV infection has virally suppressive ART, but in untreated HIV infection the risk of infection in oral sexual contacts is lower than during vaginal and anal intercourse, which supports the above assessment. Although oral sexual contacts were not documented in Opposites Attract, PARTNER1 and PARTNER2 studies, they have certainly occurred, providing additional support for the assessment. There are studies that have reported low, but detectable, levels of HIV RNA in sperm and cervical secretion in patients who do not have detectable levels of HIV RNA in plasma [17,18]. However, this is not considered relevant to the contagiousness, as no transmission of infection was seen in Opposites Attract, PARTNER1 and PARTNER2 studies. It is likely that some of the participants in these studies had low viral loads in the genital secretion, even if it was not studied.

Risk of transmission trough sharing of injection tools between people who inject drugs, in the presence of effective ART

• The risk of HIV transmission between people who inject drugs (PWID) and share injection tools is likely to decrease if the person with HIV infection is on effective ART, but there are no studies available to support this.

No studies have been published that assess the risk of HIV transmission through sharing injection tools if the person with HIV infection is on effective ART. Observational studies have shown that reduced viral load at the population level, as a result of increased use of ART, has been associated with a reduced incidence of HIV infection among PWID in British Columbia, Canada and Baltimore, USA [19,20]. However, a follow-up study showed that the reduced transmission of HIV among PWID in British Columbia was largely explained by reduced risk behaviour and only to a small extent by ART [21]. For anal and/or vaginal intercourse between PWID, there is no risk of transmission of infection if the partner with HIV meets the criteria for effective ART.

Risk of transmission from mother to child during pregnancy, childbirth and the neonatal period

• In order to protect the child, pregnant women living with HIV have an obligation to inform health care providers about their HIV infection early in pregnancy to enable preventive interventions. This applies regardless of treatment status.

• Pregnant women living with HIV on effective ART may deliver vaginally if there are no obstetric reasons for a caesarean section.

• To avoid exposing the child to risk of transmission, women living with HIV have an obligation to abstain from breastfeeding their children. This applies regardless of treatment status.

• Fertility examination and assisted reproduction treatment should be offered to women living with HIV on effective treatment using the same criteria as for women without HIV.

The very low risk of mother-to-child transmission and the advances in the field of ART, which has resulted in improved life expectancy and quality of life, has led to more PLHIV planning for a family and children. The risk of mother-to-child transmission of HIV during pregnancy and childbirth is less than 0.5 per cent if current treatment recommendations are followed [22]. This means that pregnant women living with HIV are obliged to inform health care providers about their HIV status early in pregnancy to enable preventive measures to protect the child. Data from the national surveillance systems in the UK and Ireland, where three (0.1%) of 2,309 children born to women with HIV RNA <50 copies/mL were infected [23], and follow-up data from Sweden, indicate an even lower, but not eliminated, risk of transmission.

ART significantly reduces the risk of transmitting HIV to the child during breastfeeding [24] but does not eliminate it. Women living with HIV must therefore abstain from breastfeeding.

Reduced fertility is probably more common among women living with HIV than among women without HIV infection. Fertility treatment and assisted conception are currently not generally offered to women living with HIV in Sweden. In the context of a government assignment in 2018, the Public Health Agency stated that the current regulations on donation and collection of organs, tissues and cells (SOSFS 2009:30) need to be reviewed as new knowledge has emerged. This would provide better legal support to clinics regarding fertility treatment and assisted conception to people on effective ART. However, assisted reproduction for women with HIV infection is already offered in some regions of Sweden and in other countries within and outside the EU. Regarding risk of transmission, there is no reason not to offer women living with HIV fertility examination and assisted conception treatment under the same conditions as other women.

Risk of transmission for health care staff

• The risk of transmission of HIV to staff in health and dental care from a patient who is on effective ART is considered not significant for splashes of body fluids in the eye and mucous membranes or for superficial needle pricks.

• If blood is injected, the risk is more difficult to assess, and although the risk is reduced, HIV transmission cannot be excluded.

In Sweden, there have been no documented cases of HIV transmission from patients to personnel in health care or dental care. All internationally reported cases among healthcare professionals during the period 1985–2002 have been compiled, and a majority of these have occurred in the USA [25]. A description of the cases in the USA showed that 51 cases of transmission had been registered from 1985 to 1996, but not a single case had been reported from 1999 to 2013 [26]. This change can be explained partly by reduced infectiousness from people with HIV infection on effective ART, and partly by prevented transmission of infection due to post-exposure prophylaxis. In addition, diagnostics have improved since the 1980s, which has led to increased opportunities to determine the time of infection and possible connection to events in the health care system.

Most reported cases are incidents when healthcare professionals have been pricked by a used needle during blood sampling or similar. Only a few cases include other personnel and, there are no documented cases of transmission of HIV to dental care staff. The risk of transmission of HIV through a superficial needle prick with blood from untreated PLHIV is estimated to be <0.1%. The risk of transmission has been associated with deep needle pricks, accidental inoculation, and blood with high concentrations of virus from AIDS patients, i.e. people with severe immune deficiency. The risk of transmission after accidental splashing of blood in eyes or mouth is estimated to be even lower, with only a few reported cases [25].

In incidents in health care settings when blood from a patient with HIV infection who is on effective ART is injected deeply or directly into the blood vessels, the risk of transmission is reduced but cannot be completely excluded [27,28].

In the case of a superficial needle prick or splash of blood in the eye or mouth from a patient with HIV infection on effective ART, post-exposure prophylaxis is no longer recommended in the UK [29], while the United States and others still maintain this recommendation [30,31]. RAV does not recommend post-exposure prophylaxis if it can be documented that the index case has effective ART. If this cannot be confirmed in the acute situation, it is recommended to start post-exposure prophylaxis and reassess the need when the information is available [10].

Prevention of HIV transmission to health care personnel

Health care incidents that may pose a risk of transmission of blood-borne infections should always be handled by a physician. An assessment should be made as to whether there is any risk of transmission of HIV or other infectious agents and a decision is made regarding possible prophylactic treatment, testing and follow-up. The employer assesses whether the incident should be reported as an occupational injury.

According to the Swedish Communicable Prevention Act (SFS 2004:168), PLHIV must be given individually worded practical rules by the treating physician prior to contact with health care and dental care. Persons who have a blood-borne infection are obliged to inform the health care providers of their infection in contacts that involve a risk of exposure to blood. However, this obligation does not require disclosing information about the specific infection diagnosis.

If the care contact applies to routine, simpler examinations, including blood sampling and injections, or routine dental care, and the person is on effective ART, there is no significant risk of transmission and the staff do not need to be informed. In situations involving a higher risk of penetrating stabs or cutting injuries, e.g. surgical procedures, a considerable risk cannot be excluded, and the person then has an obligation to inform the staff performing the procedure. If an incident involving risk of transmission of infection occurs, the PLHIV are obliged to inform the at-risk person about their HIV infection.

Overall assessment

Based on the current state of knowledge, RAV and the Public Health Agency of Sweden concludes that there is no risk of transmission of HIV through vaginal and anal intercourse if the person living with HIV fulfils the criteria for effective virally suppressive antiretroviral therapy. This also applies to condomless intercourse. However, there are a number of other reasons to recommend the use of a condom, in particular to protect against transmission of other STIs and hepatitis, as well as unwanted pregnancies.

For people sharing injection tools, antiretroviral therapy is considered to reduce, but not certainly eliminate, the risk of HIV transmission.

The risk of vertical transmission of infection from mother to child is very low if the woman is started on treatment well in advance of the delivery and is on virally suppressive antiretroviral therapy. This requires that relevant health care professionals know about the woman’s HIV infection early in the pregnancy.

In most contacts health and dental care contacts, there is no risk of infection if the patient has a fully suppressed HIV viral load, but there may be some risk, albeit considerably reduced, in more advanced interventions such as major surgery. In incidents that might incur a risk of transmission, the HIV infected person is obliged to inform the person at risk about their HIV status.

Disclosure statement

No potential conflict of interest was reported by the author(s).