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Truvada and the truth: is HIV prevention propelling the STI epidemic?

theguardian.com, 21/10/2018

“We were taught in sex ed that sex equals death,” says MacLean, a lifestyle consultant in New York City, “because if you were gay you were going to get Aids and you were going to die. So condoms were absolutely required.”

But in 2016, after a five-year monogamous relationship came to an end, MacLean found that the rules had been upended.

In 2012, the US Food and Drug Administration approved the drug Truvada for use as HIV prevention, as “pre-exposure prophylaxis”, or PrEP. When HIV-negative men who have sex with men (MSM) take PrEP daily as prescribed, they lower their risk of contracting the virus by an estimated 99% or more.

At first, as men around him went on PrEP and often engaged in condomless sex, MacLean resisted. “And then all it took was one drunken night when I didn’t use a condom,” he said, to make him get his own Truvada prescription.

MacLean’s condom use declined dramatically. So did his fear of HIV. But he may also have put himself at increased risk of contracting other sexually transmitted infections (STIs).

In the MSM community, a rapidly expanding STI epidemic is fueling questions about whether the steadily rising number of people who start Truvada for HIV prevention subsequently change their sexual behavior in ways that increase their risk of contracting chlamydia, gonorrhea, syphilis and, in rarer cases, hepatitis C.

‘Behavioral change’

In the US, public health officials are beginning to credit Truvada with pushing down HIV transmission rates. An estimated 180,000 Americans use PrEP, the vast majority of them MSM.

Worldwide, perhaps 100,000 more are taking it. In England, though the National Health Service has not backed the pill, many MSM are buying generic Truvada online. Australia has seen a recent dramatic increase in use, thanks in part to a study published in The Lancet HIV this month which found that putting thousands of men on Truvada was associated with a 25% one-year decline in HIV diagnoses among MSM in New South Wales.

In the first five years following PrEP’s US approval, most studies did not show convincing evidence that going on it was linked to significant sexual behavioral shifts, such as having more sexual partners, having sex more frequently or, as in MacLean’s case, using condoms less.

It has been abundantly clear that PrEP arrived amid a two-decade decline in condom use among MSM. This is a trend driven by multiple factors, including diminishing anxieties about HIV following the 1996 approval of effective treatments for the virus and, in the 2010s, an accumulation of evidence indicating that successfully treating HIV effectively blocks transmission.

This year, studies have begun to reflect what MacLean and many other gay men say they have long known: among MSM, the rising popularity of PrEP is hastening the decline in condom use. A review published in the journal Clinical Infectious Diseases in March analyzed 13 PrEP studies covering 5,000 participants. It found that most papers observed an increase in condomless sex after people started Truvada for prevention, especially in the more recent studies.

According to the review’s lead author, Michael Traeger, a research assistant at the Burnet Institute in Melbourne, “There is enough evidence now to show that some men experience sexual behavioral change following PrEP initiation. This is not surprising. Such behavioral change highlights men’s confidence in PrEP to prevent HIV acquisition.”

Following this logic, earlier PrEP studies probably did not see declining condom use because participants did not know if they were receiving a placebo, or did not yet know or have faith in how well PrEP works. The initial studies also recruited men at high risk of HIV who often already used condoms at low rates, making it harder to detect any downward shift.

Behavioral change highlights men’s confidence in PrEP to prevent HIV acquisition

Michael Traeger, Burnet Institute

Another new study, presented at a global HIV conference in Amsterdam in July, looked at condom use among more than 300 American MSM who went on PrEP. In three-month intervals, the men reported an average of 2.8 condomless sex acts before going on PrEP and 7.1 such acts while on PrEP. Among those who had stopped using Truvada, they reported 2.1 such acts in the same intervals.

Several recent studies have linked PrEP with a modest rise in STIs. Traeger’s team analyzed eight studies with 4,400 participants and found that starting Truvada for prevention was associated with a 24% increase in such diagnoses. The US study presented in Amsterdam only found one statistically significant STI-related shift in the cohort: after men stopped PrEP, the diagnosis rate for rectal chlamydia or gonorrhea infections fell by 80%.

Traeger and his colleagues studied a subgroup of nearly 1,400 MSM who participated in one of the Australian studies that swiftly scaled up PrEP use in 2016. The researchers had at least 12 months of pre-PrEP data on these men, thanks to their routine attendance at sexual health clinics where they were given Truvada. After the men started study-provided PrEP, the STI diagnosis rate increased by 71% among those taking PrEP for the first time. It did not increase significantly among those with prior Truvada experience.

The authors then controlled for the new users’ 48% post-PrEP-initiation increase in STI-testing frequency, and concluded that going on Truvada for prevention was associated with a 21% increase in STI diagnoses.

PrEP guidelines generally recommend conducting STI tests quarterly, a high frequency that may considerably reduce the time men spend infectious to others. A 2017 mathematical modeling study predicted that even if MSM dramatically lower their condom use after going on PrEP, such stepped-up testing will actually drive down rates of STIs in the overall MSM population.

But there is also evidence that some clinicians fail to keep their PrEP-using patients to the advised STI testing schedules. Additionally, the 2017 modeling study did not take into account how PrEP may have influenced the decline of condom use among MSM who are not on Truvada.

A paper published in the Lancet HIV in August analyzed recent condom use among nearly 17,000 men in Melbourne and Sydney who reported male casual sex partners. The 2016 to 2017 surge in local PrEP use, they found, was associated with a comparably swift acceleration in the proportion of men reporting inconsistent condom use, regardless of whether they took Truvada for prevention.

Matthew Golden, director of HIV and STI program for the Seattle area, expressed concern that if PrEP does contribute to widespread sexual behavioral changes in the MSM community, marginalized subgroups may be hit with higher infection rates of both HIV and STIs. In the US, PrEP is predominantly used by white MSM age 25 and older. African American MSM have by far the highest HIV rates of any risk group.

Findings about PrEP’s apparent ties to increasing STIs have led to some calls for an improved response to such transmissions. Researchers also see an opportunity to engage PrEP users in research into new forms of STI prevention, including vaccines.

But an apparent minority of prominent experts remains unconvinced. Dawn K Smith, a medical officer in HIV prevention at the Centers for Disease Control and Prevention, said: “We don’t have evidence that PrEP caused declines in condom use in the US.”

Others would prefer PrEP researchers steer away from investigating and debating related behavioral change, which is sometimes called risk compensation.

“Research regarding PrEP’s association with risk compensation and STI rates may not be productive,” says Demetre Daskalakis, deputy commissioner for the Division of Disease Control in New York City. “Resources should be focused on establishing strong PrEP services that address issues of sexual health rather than trying to demonstrate risk compensation.”

Jean-Michel Molina, a prominent PrEP investigator at the Hôpital Saint-Louis in Paris, says: “STIs should not be an excuse to deny PrEP access or to be reluctant about PrEP. That would make no sense.”

In September, a Belgian researcher argued in the journal AIDS that the increased rate of STI testing and resulting antibiotic treatment associated with PrEP may fuel the emergence of an already looming threat: drug-resistant strains of gonorrhea.

Some academics see such overtures as attempts to scapegoat Truvada with high-minded moralizing.

Sarit Golub, a psychology professor at Hunter College in New York City, argues: “Much of the risk compensation argument is a way to reassert public health’s behavioral control over sexual expression by substituting fear of STI epidemics in place of fear of the HIV epidemic. The risk compensation rhetoric has already contributed to both implicit and explicit bias and stigma that has limited PrEP access and implementation.”

Indeed, evidence suggests that clinicians who harbor stigmatizing attitudes about PrEP users are less likely to prescribe it, especially to African Americans. According to Will Nutland, the founder of the PrEP-promoting British website prepster.info, beliefs that PrEP will cause collateral damage have contributed to the NHS’s refusal to pay for the drug.

“If one of the consequences of a massive reduction in HIV incidence is an increase in STIs then I know what I’d rather see,” Nutland says. “But I don’t think it has to be an either/or. I think we can move to driving down STIs and HIV if there’s the political willpower to do so and investment in technologies, education and services.”