How I May Change My Practice Based on Results Presented at AIDS 2018

Anton L. Pozniak, MD, FRCP

Consultant Physician
Director of HIV Services

Department of HIV and Genitourinary Medicine
Chelsea and Westminster Hospital NHS Foundation Trust
London, United Kingdom

Anton L. Pozniak, MD, FRCP, has disclosed that he has received consulting fees and funds for research support from Gilead Sciences, Janssen, Merck, and ViiV.

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Released: August 10, 2018

Several studies recently presented at the 2018 International AIDS Society meeting (AIDS 2018) may have an impact on how we treat patients with HIV in the coming year. Herein, I highlight some of those key data.

Integrase Inhibitors
Much of the data at AIDS 2018 revolved around integrase inhibitors, in particular dolutegravir (DTG).

The newest IAS-USA guidelines, released during the conference, now list 3 regimens only—all 3-drug regimens based on integrase inhibitors—as “generally recommended” for treatment-naive patients:

  • Bictegravir + emtricitabine (FTC)/tenofovir alafenamide (TAF)
  • DTG/abacavir/lamivudine (3TC)

It will be interesting to see how this and other guideline panels reconcile data from GEMINI-1 and -2 wherein treatment-naive patients were successfully treated with the 2-drug regimen of DTG + 3TC. At Week 48, the 2-drug regimen was noninferior to DTG + FTC/tenofovir disoproxil fumarate (TDF) (91% vs 93% with HIV-1 RNA < 50 copies/mL, respectively). First-line therapy with this 2-drug regimen may reduce potential toxicities and the cost of having a third agent, but there are some caveats.

First, patients should demonstrate immunity to hepatitis B virus before initiation of DTG + 3TC to avoid treating active hepatitis B infection with only 3TC. Nonimmune patients should be vaccinated.

Second, because trial entry was capped at an HIV-1 RNA of 500,000 copies/mL, this strategy is not for patients with very high viral loads. I would also not use such a strategy in tuberculosis coinfection, in pregnant women, or in test-and-treat, same-day situations where viral load and resistance profiles are not usually available. (Interim analysis of phase III DIAMOND suggests that single-tablet regimen darunavir/cobicistat/FTC/TAF would be effective in this latter scenario.)

In addition, a numerically lower virologic suppression rate was observed for DTG + 3TC in those with baseline CD4+ cell count ≤ 200 cells/mm3, but patient numbers were small and there is no need to start such advanced patients on a 2-drug regimen at present.

However, in this population a 2-drug regimen worked, and the good news was that no treatment-emergent resistance was seen in the few virologic failures.

We now also have more confidence in switching virologically suppressed patients to a 2-drug regimen with DTG/rilpivirine, thanks to Week 100 data from phase III SWORD-1 and -2. This single pill spares any actual or potential nucleos(t)ide toxicity.

Reducing regimens to 2 drugs using a boosted PI or integrase inhibitor plus a reverse transcriptase inhibitor has been successful, but monotherapy is a bridge too far. Two studies of DTG monotherapy, one with switch as maintenance, confirmed what we have already seen: There is no role for this strategy in current practice, and it could lead to integrase resistance. The second study, with similar design but for those who had been treated for primary HIV infection, showed utility, but such patients are unusual and we only have 48-week cohort data thus far.

Speaking of treatment choices, perhaps an NNRTI might soon reappear in the list of guideline-preferred regimens, pending approval of doravirine. At Week 96 in the phase III DRIVE-FORWARD study, doravirine demonstrated durable virologic efficacy compared with darunavir/ritonavir, each with NRTIs, in treatment-naive patients (73% vs 66% with HIV-1 RNA < 50 copies/mL, respectively). Fewer than 1% of patients acquired doravirine resistance.

For me, the most global treatment issue of the conference was the focus on the 4 cases of neural tube defects reported from the Botswanan Tsepamo study in 426 women who received preconception DTG. With an additional 170 pregnancy outcomes between May 1 and July 15 of this year, no new cases have been reported in this subgroup. This is an early signal, and more data are required to confirm or refute whether DTG is definitely associated with a higher risk for neural tube defects

A clear message is that women should be engaged in decision making regarding ART choices, while being provided with information about the risks and benefits of DTG and ready access to reliable and effective contraception.

Patient engagement and choice are key components of undetectable equals untransmissible messaging. Reassurance about this message for men who have sex with men (MSM) came from the prospective PARTNER2 study, which confirmed no linked transmissions among more than 780 serodifferent MSM couples who had sex approximately 77,000 times without condoms during approximately 1600 couple-years of follow-up while the HIV-infected partner had undetectable virus (HIV-1 RNA < 200 copies/mL).

Moreover, on-demand pre-exposure prophylaxis (PrEP) worked in real life! In the prospective ANRS Prevenir study, no incident HIV infections were observed during a mean follow-up of 7 months in 1594 high-risk individuals receiving FTC/TDF PrEP.

Your Thoughts
Overall, data from AIDS 2018 give us a lot to think about and put into practice as we return to our clinics.

How will these emerging findings affect your patient management strategies? Join the conversation by adding your perspective to the comments section or by answering the polling question.

Jointly provided by the Annenberg Center for Health Sciences at Eisenhower and Clinical Care Options, LLC

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Janssen Therapeutics

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