By Enid Vázquez @ENIDVAZQUEZPA

The PARTNER 2 study found zero transmissions of HIV in 972 male couples where one partner has the virus and the other doesn’t, despite 75,000 acts of condomless sex acts and no use of PrEP or PEP. The men living with HIV all had undetectable viral load.

The study team wanted to expand on the findings of the PARTNER 1 trial, where most of the couples enrolled were straight. That study also found zero linked transmissions.

“PARTNER 2 provides a similar level of confidence for gay men as for heterosexual couples in PARTNER 1,” wrote lead author Alison J. Rodger, MD, of the University College London and colleagues in their conclusion.

“I think it’s very clear, the time for excuses is over,” she said during her presentation. “If you’re on suppressive therapy, you’re sexually uninfectious.”

More from Enid

On-demand PrEP succeeds

Vive la France! The ANRS Prevenir community-based study, which took place in the Paris area, found no HIV transmission in men using either PrEP or on-demand PrEP in sex with other men. PrEP prevents HIV. The Prevenir (or “prevent”) trial built on the international IPERGAY study that also found successful results with on-demand PrEP in men who have sex with men.

At this time, PrEP requires a daily pill of Truvada. The on-demand PrEP used in this study consisted of:

  • two pills of Truvada within 24 to 2 hours before first sexual intercourse, then
  • one Truvada pill every 24 hours during the period of sexual activity, with
  • one Truvada pill after the last sexual intercourse, and one last Truvada pill 24 hours after that.

“On-demand PrEP with TDF/FTC [Truvada] has been recommended as an alternative to daily PrEP for MSM [men who have sex with men] by the European AIDS Clinical Society following the results of clinical studies, but data are limited on real-world experience,” the research team noted in their study summary. Nearly 1,500 HIV-negative men enrolled in the study.

“In this ongoing PrEP cohort in the Paris region, enrolling mainly MSM at high risk of HIV acquisition, no breakthrough HIV infection was reported so far with either daily or on-demand PrEP, supporting continuing use of both dosing regimens in their population,” they concluded.

PrEP levels with female hormones

Transwomen who use feminizing hormones have worried about drug interactions with the use of Truvada for PrEP, noted Akarin Hiransuthikul and colleagues of the Thai Red Cross AIDS Research Center. Not for nothing. The team’s iFACT study found that the plasma levels of the tenofovir DF (TDF) in Truvada were affected by feminizing hormone therapy. Plasma levels of TDF were slightly lower. This suggests that Truvada for PrEP may be less effective for transwomen on the hormone treatment, although Hiransuthikul said the levels were still high enough to be effective for HIV prevention. More research is needed to see if the lower levels are clinically significant.

The hormone levels, on the other hand, were unaffected by the Truvada. Yay! Twenty women enrolled in the study.

Juluca 2-year data

ViiV Healthcare reported that, at two years out, the results of switching to Juluca continued to be non-inferior compared to staying on a three- or four-drug regimen. 

Juluca was FDA approved earlier this year. It is a two-drug single-tablet regimen of dolutegravir (brand name Tivicay) and rilpivirine (brand name Edurant).

In combined data from the SWORD 1 and SWORD 2 studies, 456 of the 513 individuals (89%) on Juluca continued to have undetectable viral load.

Two-drug therapy non-inferior to 3-drugs as initial regimen

On the coattails of Juluca, Tivicay’s maker, ViiV Healthcare, reported more good news with using it as a two-drug regimen, combined with its Epivir (3TC). (The Edurant in Juluca is from Janssen Pharmaceuticals.)

In two separate studies, GEMINI-1 and GEMINI-2, Tivicay (dolutegravir, or DTG) plus Epivir (3TC) did as well as the combination of dolutegravir plus Truvada (tenofovir DF/FTC).

Pedro Cahn, MD, of Fundacion Huesped in Buenos Aires, and colleagues reported that patients are interested in two-drug regimens to avoid greater drug exposure over their lifelong therapy, as well as minimize potential side effects. “DTG’s potency, safety, and resistance barrier make it an optimal core agent for two drugs while 3TC’s safety, tolerability, and efficacy make it an attractive partner for initial HIV-1 treatment,” they wrote.

After one year in each study, dolutegravir plus 3TC was found to be non-inferior to dolutegravir plus Truvada. In the participants taking the two-drug regimen, 91% (655 out of 716) had undetectable viral load, compared with 93% (669 out of 717) of those taking the three-drug regimen.

There were more than 700 persons in each study, all taking HIV medication for the first time. More than 20% of them started out with a high viral load of greater than 100,000 copies per mL. There were more drug-related adverse events with dolutegravir plus Truvada, as to be expected due to the TDF it contains.

Doravirine update

Merck updated its 48-week data with doravirine to 96 weeks, from the DRIVE-FORWARD study.

Doravirine continued to show non-inferiority to Norvir-boosted Prezista. Both drugs were taken along with either Epzicom or Truvada.

At 96 weeks, 73% of the doravirine group had undetectable viral load compared with 66% of the boosted Prezista group. The average CD4 T-cell count increase was 224 for the doravirine group and 207 for the Prezista group. The 766 participants in the DRIVE-FORWARD study were all taking HIV treatment for the first time.

Side effects in the doravirine arm of the study included diarrhea (17%), nausea (12%), headache (15%), and upper respiratory tract infections (13%). These rates were about the same for the Prezista group.

There was, however, a statistically significant increase in LDL cholesterol and triglycerides with Norvir-boosted Prezista. Norvir is known to increase these levels, even at lower booster doses.

Doravirine is an NNRTI medication (non-nucleoside reverse transcriptase inhibitor). The FDA has accepted a New Drug Application (NDA) for both doravirine and a doravirine single-tablet regimen (combining it with Epivir and tenofovir DF). An FDA decision is expected soon.

Dolutegravir in pregnancy

Despite low exposure levels of dolutegravir (DTG) in pregnant women living with HIV, the medication managed to bring their viral load down rapidly. That’s good news.

The DolPHIN-1 study found a more rapid decrease in viral load in pregnant women taking dolutegravir compared with those taking efavirenz.

The 60 women in the study started HIV therapy in their third trimester. According to the report, starting HIV therapy this late in the game has been associated with an inability to achieve undetectable viral load as well as increased transmission. There were no HIV transmissions in this study.

“DTG transfer across the placenta (122%) and in breast milk (3%) coupled with delayed elimination resulted in significant infant exposures potentially persisting during breast-feeding,” the research team reported. “Both regimens were well-tolerated. A total of 10 SAEs [serious adverse events] were reported in 5 mothers and 3 infants, with no significant differences between arms [the two medications].”

The DolPHIN-2 study will look at the impact of “significant infant DTG exposures related to intrauterine transfer, continued breastfeeding and delayed elimination.”

The women, all in Uganda and South Africa, took dolutegravir or efavirenz along with two HIV NRTI medications. Dolutegravir is found in Tivicay, Juluca, and Triumeq. Efavirenz is found in Sustiva and Atripla.

Birth defects have recently been associated with dolutegravir. See the following item, as well as the Briefly section of the Positively Aware July + August issue.

Dolutegravir and birth defects

Following recent warnings of the potential for neural tube defects to newborns of women taking dolutegravir at the time of conception, Rebecca Zash, MD, of the Beth Israel Deaconess Medical Center, provided an update.

In the earlier report, preliminary data showed that four out of 426 infants born to women who were taking dolutegravir at the time of conception experienced neural tube defects. This was less than one percent (0.94%), but higher than the 0.12% found among women taking a non-dolutegravir regimen at the time of conception (14 infants out of 11,300).

However, not one infant out of 2,812 whose mother started dolutegravir during pregnancy had a neural tube defect.

Researchers are looking to further surveillance to confirm any link between dolutegravir and this potential side effect, which consists of birth defects of the brain, spine, or spinal cord.

The Amsterdam Affirmation: People, Politics, Power

For every international AIDS conference, the organizer, the International AIDS Society (IAS), and its partners create a sign-on declaration. The declarations focus on needed changes to end the pandemic. This year’s declaration was “The Amsterdam Affirmation: People, Politics, Power.”

“Much has changed since the global HIV community convened at the previous International AIDS Conference in Durban in 2016. Advances in science have been significant, including widespread acceptance that HIV is untransmittable with an undetectable viral load, increased PrEP rollout, innovative treatment delivery methods, and promising developments in cure and vaccine research. But while there have been success stories, prevention efforts continue to lag and new HIV infections are still on the rise among key populations and young women and girls. These groups continue to experience high levels of structural violence and stigma. Coupled with a rising tide of populism, questionable political commitment and leadership, and declining financial resources, the HIV response is operating in a fragile environment. People, politics, and power lie at the heart of the AIDS epidemic. How these intersect will continue to be critically important in achieving the agreed global targets and universal health coverage.”

Read the suggestions of this declaration and sign on at aids2018.org.