“Profound change” in HIV clinical culture

BETWEEN 2004 and 2015, the percentage of people with a human immunodeficiency virus (HIV) infection who started antiretroviral therapy (ART) within 6 months of diagnosis skyrocketed from 17% to 53%, with yet-to-be published data suggesting that number has further climbed to over 90% since 2015.

“It’s a profound change in clinical culture,” says Professor Basil Donovan, Head of the Sexual Health Program at UNSW’s Kirby Institute.

Professor Donovan is a co-author of research, published by the MJA, which documented the 17% to 53% shift in the proportion of patients attending major Australian sexual health clinics. The authors found that a total of 917 people were diagnosed with HIV between January 2004 and June 2015, 92% of whom were men. The median CD4⁺ (white blood cell) count at diagnosis was 510 cells/μL.

“By the early 2000s, we were still dealing with the first and second generation of ART drugs, and they were pretty awful drugs – toxic,” Professor Donovan says in an exclusive InSIght+ podcast. “They would rot the peripheral nerves. A lot of us are still managing patients that were damaged as a result of those early medications.

“But they had to have them because without them, they would have died. It left the treating doctors pretty wary of basically poisoning their patients.”

As a result, until late 2007, ART was not recommended until the CD4⁺ cell count fell below 200 cells/μL.

“This threshold was raised when concerns about the toxicity of treatment eased, supported by large cohort studies that found clinical outcomes were improved when treatment commenced earlier,” Professor Donovan and his co-authors wrote in the MJA.

“Three big things happened over that period from 2004 to 2015,” Professor Donovan tells InSight+. “One was the drugs got better – a lot better. They were easier to take, mostly just one pill, once a day, minimal side effects.”

Then, in 2011, a huge breakthrough came. Cohen and colleagues published a study showing that “there was a relative reduction of 96% in the number of linked HIV-1 transmissions resulting from the early initiation of [ART], as compared with delayed therapy”.

In other words, says Professor Donovan, “he showed that if you were on treatment and you had expressed viral load, you didn’t seem to infect your sexual partner anymore”.

“Then as clinicians, we were sitting there going, ‘whoa, hang on, treating these people isn’t just an individual health issue, it’s a public health issue’.

“We still didn’t rush into treating straight [after diagnosis],” Professor Donovan says. “We didn’t want to pressure our patients into treatment in order to protect their partners.”

Another game-changer came in 2015, with the START Study.

“That showed that if you were [taking] HIV medications, your all-cause mortality was halved – not just from HIV-related conditions [but also from] general cancers, heart disease and others,” says Professor Donovan.

“That swung us. Now the guidelines say, just treat everybody.”

To meet the United Nations’ goal of eliminating the AIDS epidemic by 2030, many countries are aiming for the “‘90–90–90’ treatment target: 90% of people living with HIV should know their status, 90% of people diagnosed with HIV infection should receive treatment, and 90% of treated people should achieve virological suppression,” according to Donovan and colleagues in the MJA.

“In Australia, we’re well over 90 on the first 90. We’re about 95% on the second 90. And about 98% on the third 90,” Professor Donovan says.

A vaccine is no closer, and now is the time to return to the research laboratory, he says. There are still hot spots; Indigenous Australians, for example, are infected at twice the rate of the non-Indigenous population, and young patients are hard to keep compliant with medication.

“Young people don’t like being told, ‘look here’s a medication you’re going to have to take for the rest of your life’,” says Professor Donovan. “If it’s a middle-aged urban person, they’ll go, ‘okay’. But if you’re a teenager or in your early 20s, it’s quite something to absorb.

“We’ve had to go back to the lab and try to get the basic science better, work out exactly how this thing ticks, where the virus is vulnerable and hopefully vulnerable in a durable sort of way.

“The next move will be towards long-acting antivirals that might last a month or 3 months, or even longer.”

Could he have ever envisioned that in the heat of the mid-1980s and early 1990s when things were dire?

“I’m just pleased to have lived long enough to see it.”