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IDCM CME Issue 1-12: Updates in HIV: Key Studies from the 2019 International AIDS Society Conference on HIV Science
Author: Natasha Chida, MD, MSPH
The 10th annual International AIDS Society Conference on HIV Science was held July 21-24 in Mexico City, Mexico. The conference reviewed critical basic, translational, and clinical HIV research from around the world. The following are a few of many key studies presented at the conference that may be of interest to all providers who see patients with HIV, either as a primary provider or in consultation.
More Data on Weight Gain with Integrase Inhibitors (INSTIs): A trial in Cameroon (called NAMSAL), randomized 613 treatment-naive patients to receive either dolutegravir/lamivudine/tenofovir disoproxil (DTG/3TC/TDF) or efavirenz/lamivudine/tenofovir disoproxil for 96 weeks. Body weight was measured at baseline and at week 48. Mean weight rose +7.3% for DTG/3TC/TDF versus +5.3% for EFV/3TC/TDF; treatment-emergent clinical obesity (defined as a BMI>30kg/m2) occurred in 12% on DTG/3TC/TDF and 5% for EFV/3TC/TDF. Both findings were statistically significant.
In another trial (ADVANCE), 1053 persons who were treatment-naive and living in South Africa were randomized to receive either dolutegravir/emtricitabine/tenofovir alfenamide (DTG/3TC/TAF) or dolutegravir/emtricitabine/tenofovir disoproxil (DTG/FTC/TDF) or efavirenz/emtricitabine/tenofovir alfenamide EFV/FTC/TDF. Body weight was measured at baseline and at week 12. Results were reported by gender. In men, the mean change in weight was 5 kg, 3 kg, and 1 kg for DTG/TAF/FTC, DTG/FTC/TDF, and EFV/FTC/TDF, respectively. In women, the mean change in weight was 6 kg, 3 kg, and 2 kg. Treatment-emergent clinical obesity in men occurred in 8%, 3%, and 4% on DTG/TAF/FTC, DTG/FTC/TDF, and EFV/FTC/TDF, respectively. In women obesity occurred in 20%, 10%, and 7%.
A Phase III HIV Vaccine Efficacy Trial will be Launched in 2019. This study, called Mosaico, will join 3 other phase III vaccine efficacy studies that are already underway. It will assess whether a vaccine will prevent HIV acquisition among men who have sex with men and among transgendered people at multiple sites in North America, South America, and Europe. The vaccine is based on “mosaic” immunogens, which are elements of multiple HIV subtypes that are designed to induce immune responses against multiple global HIV strains. In Mosaic 3,800 HIV negative men and transgendered persons who have sex with men and/or transgendered people will be enrolled. The study will complement an existing phase 2b study called Imbokodo that is examining another mosaic vaccine among 2,600 women in five southern African nations.
Examining Intermittent vs Daily Antiretroviral Therapy (ART). Researchers conduced an open label, randomized, multicenter non-inferiority phase III trial to examine the efficacy and safety of a 4-day-per-week triple ART, versus daily triple therapy. 636 persons who were virally suppressed for more than 12 months and who had no resistance mutations were included in the analysis. 85% were male, and the median CD4 was 689 cells/mL. Regimens consisted of: 1 nucleoside reverse transcriptase inhibitor (NRTI) combination (56.3% TDF/FTC, 16.3% TAF/FTC, 27.4% ABC/3TC) and a third agent: 6% protease inhibitor (PI), 46% non- nucleoside reverse transcriptase inhibitor (NNRTI), 48% integrase inhibitor (InSTI). At 48 weeks the treatment success in the 4-days-a-week therapy was non-inferior to daily therapy (95.6% vs 97.2% success, respectively). There was no difference in adverse events; 6 participants in the 4-day-a-week arm and 4 in the daily arm experienced virologic failure; of these, 2 and 1 had new resistance mutations, respectively.
A New Drug Class Is on the Horizon. MK-8591 (Islatravir) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI), and is the first drug in its class. In this phase 2B randomized, double blind trial, the safety and efficacy of Islatravir combined with doravirine/lamivudine (DOR/3TC) was compared to doravirine/lamivudine/tenofovir disoproxil (DOR/3TC/TDF) with placebo. Participants randomized to the study arm received either 0.25 mg of Islatravir, 0.75 mg, or 2.25 mg. 121 participants were included; 92.6% were male, and 22% had an HIV-1 RNA of >100,000 copies/mL. At 24 weeks, persons who obtained virologic suppression were then switched to a combination of Islatravir and DOR. Efficacy endpoint was the proportion of persons at week 48 with virologic suppression (HIV RNA<50 copies.mL). At week 48, 89.7%, 90.0%, and 77.4% of participants achieved virologic suppression in the 0.25mg, 0.75mg, 2.25mg dose of Islatravir respectively, compared to 83.9% with DOR/3TC/TDF. Six persons experience virologic failure by week 48; 5 in the Islatravir group and 1 in the DOR/3TC/TDF group. None had resistance to the study drugs. No serious adverse reactions were reported in the Islatravir participants
Preexposure Prophylaxis (PrEP) Drug Eluting Implant Shows Promise. In this phase 2B randomized double blind trial, the safety, tolerability, and PK profiles of an implant containing Islatravir (see above) was tested in 16 healthy participants who did not have HIV. Eight participants received a dose of 54 mg, while the others received 62 mg. The implant was in place for 12 weeks; the subjects were then followed for 4 weeks. Both implant doses had concentrations above the PK threshold at 12 weeks; the 62 mg implant was projected to be above threshold for at least 12 months. There were no discontinuations due to an adverse event, and no severe adverse events. Adverse events that were noted were site-related (hematoma, pain, erythema, induration, pruritus).
More about this year’s IAS conference, including webcasts for many presentations, can be found online: http://www.ias2019.org/.
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- Hill A, et al. Progressive rises in weight and clinical obesity for TAF/FTC/DTG and TDF/FTC/DTG versus TDF/FTC/EFV: ADVANCE and NAMSAL trials. Abstract 4772 presented at: International AIDS Society Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico.
- National Institutes of Health. NIH and partners to launch HIV vaccine efficacy trial in the Americas and Europe. Accessed August 20th, 2019.
- Landman R, et al. ANRS 170 QUATUOR 4/7 days maintenance strategy in antiretroviral treated adults with HIV-1 infection: an open randomised parallel non-inferiority phase III trial. Abstract 4817 presented at: International AIDS Society Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico.
- Molina JM, et al. MK-8591 at doses of 0.25 to 2.25 mg QD, in combination with doravirine establishes and maintains viral suppression through 48 weeks in treatment-naïve adults with HIV-1 infection. Abstract 4789 presented at: International AIDS Society Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico.
- Matthews RP, et al. First-in-human trial of MK-8591-eluting implants demonstrates concentrations suitable for HIV prophylaxis for at least one year. Abstract 4843 presented at: International AIDS Society Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico.