Condomless sex and HIV transmission among serodifferent couples: current evidence and recommendations

Abstract

Human immunodeficiency virus (HIV) infection remains a global pandemic. The primary driver of HIV incidence is sexual transmission between serodifferent individuals. Condoms, when used consistently and correctly, are effective at preventing sexually transmitted HIV infections and are considered an integral component of a comprehensive approach to HIV prevention. However, the demonstrated effectiveness of antiretroviral therapy (ART) to prevent HIV transmission, known as treatment as prevention and of pre-exposure prophylaxis, have raised an intriguing dilemma on the necessity and additive preventive benefit of condom use among individuals in serodifferent relationships utilizing these prevention strategies. Recent published evidence, although of limited follow-up duration, has shown no linked HIV transmissions with condomless sex among serodifferent couples where the infected partner was on ART and virologically suppressed. This paper will review the evidence surrounding HIV transmission risk among serodifferent couples with and without the use of condoms and will highlight factors that increase or attenuate this risk. It will also address the important benefits that condomless sex offers couples. This paper aims to provide a template for providers to have personalized discussions with their patients, particularly those with an HIV-positive sexual partner, around their individual risk of HIV transmission and the role of condom use.

Keywords:

• HIV transmission
• serodiscordant
• serodifferent
• condomless sex

Introduction and epidemiology

Human immunodeficiency virus (HIV) infection remains a global pandemic with an estimated 36.7 million people living with the virus [1]. In 2015, there were 2.1 million new infections [1]. In the United States, there are 1.2 million adults and adolescents living with HIV infection, and over 40,000 new cases occur each year [2]. HIV disease contributes significantly to morbidity and mortality especially among vulnerable populations – it is the most common cause of death among reproductive age women globally and among adolescents in Africa [3].

To date, public health efforts to curb the HIV epidemic have included promotion of risk reduction strategies including use of condoms, male circumcision, expanded HIV testing programmes and the successful scale-up and improved utilization of antiretroviral therapy (ART) by eligible infected individuals, particularly over the past decade. These efforts have resulted in significant reductions in new infections and thereby, the stabilization of the global prevalence of HIV infection [1]. HIV infection is now a manageable chronic disease, and for those who use ART consistently, there is significantly increased life expectancy and reduced transmission risk. With the improved health and longevity of people living with HIV, a subset of them engage in sexual relationships with partners who are HIV negative; these are termed serodifferent or serodiscordant relationships. Prevention of HIV transmission among these partners remains a concern for the individuals themselves and their healthcare providers.

While behaviour-modifying risk-reduction strategies, including the recommendation for condom use with all sexual encounters, have been the traditional HIV prevention approach, it has been recognized that these measures alone are insufficient to achieve significant and sustained reductions in HIV incidence [4]. Recent studies have provided evidence for novel and successful biomedical (ART based) prevention strategies that result in dramatic reductions in HIV transmission when effectively applied [5,6]. These include treatment as prevention (TasP), where HIV-infected partners in serodifferent relationships are treated with ART with the goal of reducing or eliminating the virus in blood and bodily fluids to prevent transmission and pre-exposure prophylaxis (PrEP) where the uninfected partners receive ART to prevent acquiring infections.

Due to the protection against HIV infection offered by these strategies, the safety of condomless sex (CLS) in serodifferent couples has emerged as a topic of interest. The question now frequently arises within the clinical context as to if, and in which situations, providers could advise couples that they may participate in CLS with an acceptable very low risk of HIV transmission. This paper will review the available data on the risks and rates of HIV transmission among serodifferent couples, based on individual patient risk factors, type of intercourse and virologic parameters of the HIV-infected partner. This paper will also discuss the biopsychosocial considerations of CLS among serodifferent couples and would offer medical providers a template to guide more effective HIV prevention counselling, enabling serodifferent couples to make an informed decision of their personal acceptability of HIV transmission risk.

Sexual transmission of HIV infection

Counselling patients on safe sexual practices is integral to preventing incident infections, as sexual contact remains the predominant modality of HIV transmission [2]. Male-to-male sexual contact and heterosexual contact account for an estimated 67% and 24% of new infections acquired among adults and adolescents in the United States each year, meaning that over 90% of new HIV infections are sexually transmitted [2]. While evidence-based HIV risk reduction strategies exist, including condom use with sexual encounters, self-report on adherence with condoms suggest non-use or incorrect use is common, thereby limiting its real-world effectiveness [7–11]. Even in those who intend to consistently use condoms, adherence may be suboptimal due to substance use and other relationship dynamics that impact the successful negotiation for and/or utilization of condoms during sexual intercourse [12–15]. In addition, breakage and slip may occur resulting occasionally in HIV exposure and potentially transmissions.

Estimates of HIV transmission risk vary greatly, depending largely on the type of sexual act, whether ejaculation occurs (for acts involving males), and individual patient factors such as the presence of genital coinfections and male circumcision status [16–20]. The highest risk of sexual transmission is among individuals (MSM or heterosexual), who practice receptive anal intercourse, with a 1.38% risk of infection per exposure, followed by insertive anal intercourse with an estimated 0.11% risk per exposure [16]. Penile–vaginal intercourse has a lower risk of transmission for either partner, with the female and male having a 0.08% and 0.04% risk per sexual act, respectively. Transmission of HIV through oral sex and between female sexual partners is exceedingly rare [16,21].

Evidence-based strategies to decrease HIV transmission among individuals in serodifferent relationships

Condom use among HIV risk groups: adherence and effectiveness

Condoms are highly effective in preventing HIV transmission; however, many individuals in serodifferent relationships are at high risk of acquiring HIV infection due to suboptimal condom use. In one study, prior to initiation of ART by the infected partner, 17% of serodifferent couples self-reported CLS, with MSM (20%) and heterosexual women (14%) reporting higher frequencies than heterosexual men (10%) [7]. A study performed in South Africa reported CLS occurring in 24.8% of serodifferent couples prior to initiation of ART [10]. Among HIV-diagnosed MSM in the United States, the prevalence of CLS (unprotected anal intercourse (UAI)) with partners of negative or unknown serostatus was 13% and 16%, respectively [22].

Poorer rates of condom use have been reported among heavy alcohol users, with 58% of HIV-positive South Africans, in one study, reporting CLS with partners of either unknown or negative HIV serostatus [13]. Younger age is also a risk factor for CLS, with 45.6% of MSM less than 25 years of age reporting UAI with ejaculation with their primary partners, compared with 28.6% and 30.3% for men of age groups 25–30 years and greater than 30 years, respectively (p < .05) [15]. Only 59% of participants in this study who were aware of their and their partner’s serostatus reported being in a seroconcordant (both seronegative) relationship. In one US study, MSM aged less than 25 years also had an increased likelihood of contracting HIV compared with those older than 30 years (OR 1.31, p = .03) and sexual risk behaviours including CLS likely explain this observation [23].

The protective efficacy of condoms for HIV transmission is well established. Meta-analyses of existing data have shown that consistent condom use reduces HIV transmission among serodifferent heterosexual couples by approximately 70–80% compared with non-condom users [24–26]. The protective effect may be closer to 70% for MSM [9]. The challenges with condom use are varied and include suboptimal availability in resource limited settings, perceived interference with sexual intimacy and satisfaction, and incorrect or inconsistent use, the latter occurring for many reasons including individual preferences [11,27].

HIV treatment as prevention (TasP)

For individuals in serodifferent relationships, the risk of HIV transmission can also be significantly decreased by consistent ART use by the seropositive partner. This was demonstrated by the HPTN 052 trial, a randomized control trial comparing the impact of early (immediate) versus delayed initiation of ART (started if CD4 count <250 at two consecutive visits or an AIDS-defining illness occurred) on HIV transmission among predominantly heterosexual serodifferent couples enrolled in nine countries [5]. The primary outcome was the rate of genetically linked HIV infections determined by an intention-to-treat analysis. Study investigators offered counselling on sexually transmitted infection (STI) prevention and condom use to HIV-negative partners.

Among 1763 couples enrolled in the study, approximately 95% reported full compliance with condoms, and the same percentage reported 0–1 sexual partners during the 3-month period prior to study enrolment. After a median of 1.7 years of follow-up, the study was prematurely terminated based on interim analysis showing a significant reduction in HIV transmissions in the early therapy group. In total, 39 HIV-1 transmissions occurred. Of these, 28 were linked to the primary partner, with 27 occurring in the delayed group and one in the early group, with a hazard reduction (HR) of 0.04 (p < .001). The lone-linked infection in the early group occurred in the first three months of HIV therapy, a time when serum viral load (VL) is often still detectable [28,29]. The linked infections in the delayed therapy group all occurred while the HIV-positive partner was not taking ART. It can be inferred therefore that the unlinked infections represent acquisition of HIV from other partners rather than the primary partner. Longer follow-up of the same cohort showed that the efficacy of the treatment as prevention strategy dropped to 93%, with transmission occurring in individuals in serodifferent relationships where the infected partner had either not achieved full virologic suppression or experienced treatment failure [30].

This study demonstrates the profound impact that ART for TasP can have. While patients in the HPTN 052 trial had access to ART, condoms and risk-reduction counselling, even in resource-poor settings, ART alone was associated with a 77% decrease in HIV transmission in serodifferent couples [31]. However, limitations of this approach are also apparent. TasP does not prevent infections where seronegative partners in serodifferent relationships have CLS outside their primary relationship, or when treated sexual partners fail to achieve full virologic suppression or experience treatment failure.

Pre-exposure prophylaxis (PrEP)

PrEP is a novel prevention tool that has achieved prominence in recent years. This strategy involves the use of a two-drug combination antiretroviral regimen to prevent HIV infection among at-risk seronegative individuals. This approach has been shown to be effective in preventing incident HIV infections in all HIV risk groups. The PROUD study evaluated the efficacy of PrEP among MSM who reported practicing CLS [32]. These individuals had high HIV risk characteristics; about 65% were diagnosed with an STI within the previous year, and about 45% used drugs linked with sexual disinhibition. Participants were randomized to receive either emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) immediately, or deferred to one year into the study. The results demonstrated significantly fewer HIV infections in the immediate group compared with the deferred group (1.2 cases versus 9.0 cases per 100 person-years, p = .0001). This difference was detected despite more than a third of individuals in the deferred group using at least one course of post-exposure prophylaxis. In this study, to prevent one HIV infection, 13 individuals would need to take PrEP for 1 year.

Of the five participants in the immediate group who contracted HIV, three were found to be positive at the time of or within 1 month of study enrolment and the other two patients were likely noncompliant with PrEP therapy. This suggests that no infections occurred while participants were compliant enough with PrEP therapy to achieve protective levels, even in this high-risk population. Similar studies performed among heterosexual couples have also shown that PrEP is an effective intervention in preventing HIV transmission [6,33] such that for couples wishing to achieve pregnancy, PrEP use by the uninfected partner may allow for safe CLS without the requirement for assisted reproductive procedures.

One of the frequently cited concerns with PrEP is the phenomenon of risk-compensation, in which individuals on PrEP disuse condoms with sexual encounters as they feel “protected” by the biomedical intervention, placing them at risk of both HIV and non-HIV STIs. However, in the PROUD study, there was no significant difference in the incidence of bacterial STIs between the immediate and deferred group (57% vs. 50%; p = .74), though this still represents a high incidence of STIs in both groups. This study did show a significantly greater proportion of men in the immediate PrEP group participating in condomless anal sex with 10 or more partners as compared with the deferred group (21% vs. 12%; p = .03). As noted earlier, condomless anal intercourse represents the highest risk sexual activity for acquiring HIV [16]. This supports the concern that some individuals on PrEP therapy may participate in higher-risk activities due to the protection against HIV offered by PrEP.

It is important to mention that in PrEP studies, participants receive risk reduction counselling, are offered and counselled on use of condoms and receive post-exposure prophylaxis, such that the reported efficacy of PrEP may not be solely attributable to the biomedical intervention alone. The importance of multimodal prevention, such as condom use and PrEP, cannot be overemphasized and is exemplified in the case of a Canadian male who contracted HIV, while adherent on PrEP therapy after participating in CLS. The patient reported intentional cessation of condom use after establishing PrEP therapy, despite participating in high-risk behaviours including predominantly receptive anal intercourse [34]. Genetic testing revealed that his acquired viral strain was resistant to tenofovir and emtricitabine, including 38-fold resistance to FTC and 1.3-fold resistance to TDF, the components of his PrEP [35].

A similar case was also reported where an individual who was fully adherent to PrEP acquired HIV infection by exposure to a sexual partner with a multidrug-resistant virus [36]. Patients exposed to PrEP medications may be more likely to acquire resistant strains, although their absolute risk of HIV infection is much lower [32,35]. This risk also includes patients taking PrEP during the acute phase of HIV infection or exposed to HIV soon after initiating PrEP [37,38]. While it is rare for individuals with sufficient levels of antiretrovirals to contract HIV, these cases demonstrate that infection can occur despite high PrEP compliance, and condom use may offer a second line of protection in the event of PrEP failure.

Evidence is still equivocal regarding whether a significant risk compensation effect occurs in studies of PrEP users, but certain individuals do report riskier behaviour, and therefore, the risks of CLS while on PrEP should be raised with all individuals initiating it [32,39–42]. However, HIV transmission risk still remains very low in patients fully adherent to PrEP and in several studies, in spite of risk compensation behaviours, no significant differences in terms of clinical outcomes including HIV transmission and acquisition of STDs were observed [32,39]. Therefore, knowing that a patient may undertake risk compensation should not preclude them as a candidate for PrEP therapy; indeed, these patients may be at higher risk of HIV and benefit most from PrEP.

Non-occupational post-exposure prophylaxis (nPEP)

Non-occupational post-exposure prophylaxis (nPEP) is also an option for reducing the risk of HIV acquisition. This typically involves individuals taking three-drug ART for 28 days, starting within 72 h of a known or possible HIV exposure [43]. However, data supporting nPEP are somewhat limited, and due to ethical considerations, there are no randomized controlled trials comparing nPEP to placebo [43,44].

Most of the available data on HIV transmission with nPEP comes from MSM studies, with one study showing that 88% of individuals who accessed nPEP at their clinic were MSM [45]. Those who use nPEP tend to be those who engage in high-risk sexual practices; therefore, nPEP use may serve as a marker for HIV risk. One study of MSM showed that individuals using nPEP were at significantly higher risk of HIV infection than non-users (HR 2.67, 95% CI: 1.40–5.08, p = .003) [46]. A retrospective study of MSM seeking nPEP showed an incidence of HIV infection of 2.2 cases/100 person-years [45]. Another study of MSM seeking nPEP after unprotected receptive anal intercourse found an overall HIV incidence of between 1.1 and 2.2 cases/100 person-years depending on the nPEP drug-regimen prescribed [47].

However, unlike with ART and PrEP, which typically require the establishment of a long-term doctor–patient relationship, nPEP may be acquired from emergency departments or STI clinics following high-risk sexual exposures. Follow-up in these patients may therefore be limited [44]. Additionally, nPEP use may not alter future risk-taking behaviour [46]. As a result, patients may subsequently require more than one course of nPEP, which would further expose them to the risk of medication side effects [43]. Given these limitations, nPEP is not recommended as a long-term strategy for reducing HIV infection, and more sustainable options, such as PrEP and condom use, are recommended [43,44]. Certainly, most individuals seeking nPEP are likely to be optimal candidates for PrEP.

ART and viral suppression in serum and genital secretions

Among individuals in serodifferent relationships where CLS is being considered, it is essential to ascertain the duration of time that the seropositive partner has been on ART, and their virologic suppression status. Transmissibility of HIV is primarily related to the viral RNA level both in the serum and in genital secretions, both of which are largely dependent on the use and duration of ART therapy [5,28,29,48–50]. This relationship was clearly demonstrated with the observation that suppression of serum HIV VL occurred in 65.3%, 84.8%, 89.1% and 90.9% of patients after 3, 6, 9 and 12 months of ART exposure, respectively [28]. The six-month cut-off is therefore often used as an approximation of when the majority of patients adherent to ART can expect to be virally suppressed, with concurrent suppression of virus in the genital secretions also becoming more likely [28,50]. However, in clinical practice, testing for presence of the virus in genital secretions is not routinely performed.

Multiple studies have shown that viral compartmentalization occurs, and in patients with an undetectable serum VL, the virus may persist in the genital secretions [28,29,51–53]. A study of heterosexual African males showed that even when serum HIV RNA levels were suppressed, 8% of patients still had detectable seminal levels of HIV RNA, although 82% of these patients had low seminal levels of <1000 copies/mL [29]. A similar study found that 6–8% of MSM with a suppressed serum VL had detectable virus in their genital secretions [54]. In one study, during the first 6 months following ART initiation, 8% of women and 9% of men with an undetectable serum VL (<40 copies/mL) had detectable endocervical or seminal HIV RNA, suggesting persistent shedding of virus despite viral suppression in the blood [28]. In this study, three phylogenetically linked HIV infections were observed among the serodifferent couples in the first 6 months of ART, while no linked infections were observed when the seropositive patient had been on ART for more than 6 months. These data suggest that transmission events do occur before virologic suppression is achieved.

Though the clinical significance of detecting virus in genital secretions despite a suppressed serum VL with respect to transmission risk remains unknown, the seminal levels of HIV RNA appear to be low in patients with a suppressed serum VL, supporting a low rate of transmissibility [29]. In one model of male-to-female transmission, the estimated probability of transmission when seminal VL was suppressed (<1000 copies/mL) was 3 per 10,000 acts of sexual intercourse, though this estimate is likely higher with anal intercourse [55]. Patients should therefore be made aware that an undetectable serum VL does not necessarily imply the absence of virus in genital secretions particularly during the first 6 months of initiating ART. HIV-negative partners in serodifferent relationships should generally be counselled on alternative methods of HIV prevention, such as PrEP and condom use, especially during that vulnerable period.

In counselling individuals regarding CLS, there should also be transparency among both partners regarding the state of the seropositive partner’s viral suppression. One study found that the prime determinant of condom use among MSM was the seronegative partner’s perception of the seropositive partner’s viral suppression [56]. In cases where the serum VL was thought to be low, patients were more likely to participate in CLS. Of concern was the observation that both the seropositive and seronegative partners over-estimated the degree of viral suppression. Perception of a low risk of HIV transmission in serodifferent couples is a known risk factor for acquisition of HIV infection, and in the PARTNER study, a very low perception of the risk of HIV transmission was the main reason cited by patients reporting CLS [8,56–58].

STIs and HIV transmission

While ART and PrEP are very effective at reducing the transmission of HIV, these methods do not offer the barrier protection provided by condoms against certain non-HIV anogenitally acquired bacterial STIs. The World Health Organization (WHO) estimates the total yearly incidence of these infections to be close to 500 million [59]. In 2012, there were 145 million cases of trichomoniasis, 130 million cases of chlamydia, 75 million cases of gonorrhoea and 6 million cases of syphilis [60]. Numerous STIs, including Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum (syphilis) and human papillomavirus (HPV), are associated with an increased risk of HIV infection (Table 1).

Table 1. Studies assessing the association between sexually transmitted infections (STIs) and HIV transmission.

Study population	Infection	Increased risk of HIV transmission (n-fold), 95% CI	Reference(s)
Men	HSV-2 seropositive	Adjusted RR 2.7 (1.9–3.9)	[79]
Women	HSV-2 seropositive	Adjusted RR 3.1 (1.7–5.6)	[79]
Heterosexual women	Incident HSV-2	HR 5.35 (3.06–9.36)	[63]
Heterosexual women	HSV-2 seropositive	HR 3.7 (2.45–5.55)	[63]
Heterosexual men and women, MSM	HSV-2 seropositive	RR 2.1 (1.4–3.2)	[80]
Heterosexual men and women, MSM	HSV-2 seropositive	OR 3.9 (3.1–5.1)	[80]
Men	HSV-2 seropositive	Adjusted IRR 2.78 (1.64–5.68)	[66]
Men	Incident HSV-2	Adjusted IRR 5.28 (CI 2.79–9.98)	[66]
MSM	HPV (one type) HPV (2 or more types)	Adjusted HR 2.0 (0.61–6.5) Adjusted HR 3.5 (1.2–10.6)	[81]
Men	High-risk HPV	Adjusted IRR 3.76 (1.83–7.73)	[82]
MSM	Interval diagnosis of anal warts	HR 3.63 (1.62–8.14)	[83]
Heterosexual men and women	The presence or history of genital ulcers	Per-act infectivity 5.3 (1.4–19.5)	[20]
MSM	One rectal GC or CT infection in previous two years	Multivariate HR 1.87 (0.74–4.71)	[84]
MSM	Two rectal GC or CT infections in previous two years	Multivariate HR 8.85 (2.57–30.40)	[84]
MSM	Early syphilis	Multivariate HR 4.04 (1.19–13.79)	[84]
MSM	Interval gonorrhoea	HR 7.12 (2.05–24.75)	[83]
Heterosexual women	Incident gonorrhoea	HR 5.46 (3.41–8.75)	[63]
Heterosexual women	Altered vaginal flora	HR 2.12 (1.50–3.01)	[63]
Heterosexual women	Intermediate flora	HR 2.02 (1.39–2.95)	[63]

CT: Chlamydia trachomatis; GC: Neisseria gonorrhoeae; HPV: human papillomavirus; HR: hazard ratio; HSV-2: herpes simplex virus-2; IRR: incidence rate ratio; MSM: men who have sex with men; OR: odds ratio; RR: relative risk.

STIs are a common finding in individuals at risk of HIV infection. In the PARTNER study alone, nearly 20% of MSM and 6% of heterosexual men and women reported an STI occurring during the study period (median of 1.3 years) [8]. This is important as STIs contribute to increased HIV risk in several ways. STIs disrupt the integrity of the mucosal barrier, facilitating entry of HIV, particularly the ulcerative STIs [17,18,20]. For individuals with HIV infection, STIs are associated with higher levels of HIV in genital secretions [17,51,61]. In one review, urethritis and cervicitis were associated with increased HIV levels in genital secretions, with odds ratios (ORs) of 3.1 and 2.7, respectively [61]. HIV compartmentalization in genital secretions, even with undetectable serum VL, may result in transmission [52].

Prevention of STIs as a means of reducing HIV infections has been a topic of interest. Genital herpes (HSV-2) particularly is thought to play a pivotal role in perpetuating the HIV epidemic in Africa, where the population attributable risk (PAR) for HSV-2 is thought to be a staggering 15–30%, with one study estimating the PAR to be as high as 50% [62,63]. In one study of HIV-serodifferent heterosexual couples, condom use decreased the risk of male-to-female transmission of HSV-2 by 96% and female-to-male transmission by 65% [64]. Once individuals acquire HSV-2, they are at higher risk of both HIV transmission and infection [62,63,65,66]. This risk persists even with treatment of HSV-2, despite a reduction in genital ulcers and decreased HIV-1 VL in genital secretions [67,68]. Although the data suggest that prevention and prompt treatment of STIs should play an important role in reducing HIV transmission, the association between HIV and non-HIV STIs may to some extent be confounded by the shared risk factor for high-risk behaviours in these individuals [66]. Furthermore, convincing data demonstrating the effectiveness of STI screening and treatment as a means of preventing HIV is lacking [67–70].

As an HIV prevention strategy, condoms also offer the added benefit of preventing other STIs. However, quantifying the effectiveness of condoms for STI prevention can be challenging, limited by bias and flaws in study design [27,66,71]. For example, an individual may report condom use during 100% of sexual encounters, though they may not use the condom through the full encounter. Alternatively, individuals who use condoms more frequently may engage in more risky behaviour. These factors may attenuate the measured protective effects of condoms in studies [27]. Despite this, the majority of the studies on condom use have shown a reduction in STIs, though results vary widely. In one study, men who were consistent condom users had lower risks of chlamydia (adjusted odds ratio (aOR) 0.66, 95% CI: 0.60–0.73), gonorrhoea (aOR 0.87, 95% CI: 0.81–0.94) and genital herpes (aOR 0.73, 95% CI: 0.61–0.88) compared with non-users [72]. Women reporting consistent condom use had reductions in chlamydia (OR 0.74, 95% CI: 0.65–0.84), gonorrhoea (aOR 0.71, 95% CI: 0.63–0.80) and trichomoniasis (OR 0.87, 95% CI: 0.78–0.97), compared to non-users. However, comparing all condom users (consistent and inconsistent) to nonusers yielded very different results; in men, there was no significant difference in rates of chlamydia or gonorrhoea, though a reduction in genital herpes was still noted (aOR 0.79, 95% CI: 0.71–0.89). In women, while lower rates of gonorrhoea were seen with all condom users (aOR 0.89, 95% CI: 0.83–0.96), rates of chlamydia were higher (aOR 1.18, 95% CI: 1.07–1.30) compared with non-users.

Another study of female sex workers demonstrated a 26% reduction in chlamydia (p = .04) and a 62% reduction in gonorrhoea (p < .001) with consistent condom use [73]. In a study of patients with a known exposure to a partner with chlamydia or gonorrhoea, significant reductions in these STIs were seen in consistent users (adjusted prevalence OR 0.42, 95% CI: 0.18–0.99) [74]. This emphasizes the importance of consistent rather than intermittent condom use. Interestingly, one study showed significant reductions in non-viral STIs only with consistent and correct condom use (OR 0.41, 95% CI: 0.19–0.90, p = .026), but not with consistent use alone (OR 0.75, 95% CI: 0.42–1.32, p = .32 [27]. Despite the limitations of the evidence for condom efficacy for non-HIV STIs, but more due to biological plausibility of a protective effect, condoms remain an integral tool for STI prevention with the additional benefit of reducing HIV transmission. This should be taken into consideration when advising individuals on the risks of CLS.

Why condomless sex matters: barriers and facilitators to condom use

Medical providers have been wary of supporting CLS in HIV-serodifferent couples because of the concern that no alternative method of HIV prevention is guaranteed to be 100% effective. Prevention of STIs and unwanted pregnancy are usually the primary concerns for providers; however, there are also potential social, cultural and psychological benefits to CLS. Medical providers may feel that these benefits do not sufficiently justify the concomitant risks of CLS, particularly in serodifferent couples where the risks of HIV transmission might intuitively seem high. However, as this paper will demonstrate, in certain conditions the risk of HIV transmission among serodifferent couples can be very low, so that the potential benefits of CLS may be realized.

Reasons individuals commonly participate in CLS include improved sensation and sexual pleasure, improved partner intimacy, greater perceived trust and in some cases the desire to conceive a pregnancy. Concerns and limitations with condoms include technical difficulties with use, fear of losing an erection, interruption in the flow of the sexual encounter, difficulty negotiating use, unplanned sexual intercourse, substance use prior to intercourse and not having a condom available [75,76]. Some MSM specifically report lack of lubrication, discomfort and pain when using condoms for anal intercourse [75]. Religious and cultural beliefs may also be barriers to the use of condoms. On the other hand, production and types of condoms have expanded, and materials, range of sizes and a variety of textures and additives have resulted in improved uptake and accessibility. In reality, it would be idealistic for providers to expect consistent condom use among all of their patients in serodifferent relationships. Therefore, an open discussion between patients and their providers that considers benefits and harms to the patient, as well as explores their motivations to engage in CLS are critical to successful HIV risk reduction counselling.

HIV transmission with condomless sex: real-world observation

The PARTNER trial, using an observational study design, assessed the risk of HIV transmission during CLS among serodifferent couples, heterosexual and MSM, where the seropositive partner was taking ART with a suppressed serum VL (<200 copies/mL) [8]. The study included 888 couples in the analysis, and over 1200 couple-years of follow-up. During this study, no phylogenetically linked infections were observed. However, 11 unlinked infections were observed in the study population, (10 MSM and 1 heterosexual), with eight of these patients reporting CLS with a partner outside of their primary relationship. The rate of linked HIV infection in this study was estimated to be zero when the seropositive partner was virally suppressed with ART, with a 95% upper limit of the confidence interval of 0.30 per 100 couple-years, suggesting a very low rate of transmission.

While we anxiously await longer term data from the PARTNER study, the study findings have some important lessons. While no linked infections were observed in this study, over time, assuming the true rate of HIV infection lies near the higher end of the confidence interval, there is still a potential risk of HIV transmission among couples engaging in CLS, particularly in higher risk groups such as MSM, or in couples where the seronegative partner practices receptive anal intercourse. The observation of HIV transmissions outside primary relationships raises the importance of enquiring about alternate partners when counselling patients about CLS, and for patients with multiple partners, strongly advising the use of additional strategies such as condoms and/or PrEP. However, individuals with sexual partners outside their primary relationship were found in one study to have lower adherence to PrEP [77].

Summary and recommendations

When suggesting method(s) of HIV prevention to serodifferent couples, a thorough sexual history is integral, particularly if the patients are interested in CLS. This should include the type and frequency of sexual intercourse, the presence of sexually transmitted infections including genital HSV, circumcision status, frequency of condom use, the presence of partners outside of the primary relationship, duration of treatment and adherence of the seropositive patient to ART, interest of the seronegative patient in PrEP, and a general assessment of risk-taking behaviour which includes sexual impulsivity or unplanned sexual encounters and drug or alcohol use. By having a provider assess and explain the individualized risk, serodifferent couples can make an informed decision on whether to use TasP, PrEP, condoms or a combination of these, as a means to reduce the risk of HIV transmission. This decision should be made in conjunction with the lifestyle preferences and degree of risk acceptable to the couple, which may vary greatly.

Although there are circumstances in which couples may accept a certain level of risk with CLS, we propose several evidence-based considerations when discussing CLS with respect to HIV transmission. Firstly, ideally, all adults in serodifferent sexual relationships with HIV infection should be on ART as has been endorsed by the WHO [78]. Secondly, couples where the seropositive patient has not achieved full viral suppression should be counselled to use condoms consistently during intercourse, and PrEP may be offered to the uninfected partner, as the risk of HIV transmission during CLS would be considered to be unacceptably high. Thirdly, given the significant number of unlinked infections that were observed in the HPTN 052 and PARTNER studies, patients should be strongly advised to consistently use condoms, with or without PrEP, during intercourse with partners outside their primary relationship. This is particularly true for alternate partners who are HIV positive or have an unknown serostatus.

We suggest the following conditions in which serodifferent couples may undertake CLS with their primary partner, with a negligible risk for HIV transmission. These conditions should all be met prior to considering suggesting CLS as an option:

1. The seropositive partner is fully adherent to ART

2. The seropositive partner has been on ART for greater than 6 months, and

3. The seropositive partner’s serum VL is suppressed (<200 copies/mL is acceptable)

In addition to the above conditions, it would be preferable if there were no clinical symptoms or signs of STIs, particularly genital HSV in either partner. PrEP for the uninfected partner may offer additional protection against HIV transmission. Providers would do well to ensure that counselled individuals have the capacity to understand the intricacies of their choice.

It is important that healthcare providers approach discussions around CLS in a non-judgmental manner and be willing to engage in shared decision-making when counselling individuals in serodifferent relationships. This will enable select serodifferent couples to make an informed choice about the risks and benefits of CLS with respect to the risk of HIV transmission, with the opportunity for improved risk assessment, lifestyle counselling and uptake of risk reduction interventions.

Disclosure statement

The authors report no conflicts of interest.