DURBAN, SOUTH AFRICA – Maraviroc-containing regimens for daily oral pre-exposure prophylaxis in women at risk for HIV infection showed good safety and tolerability in a phase 2 study, the first randomized trial of PrEP ever conducted in U.S. women, Roy M. Gulick, MD, reported at the 21st International AIDS Conference.
No new HIV infections occurred in the 188 women who participated in the 48-week, randomized, double-blind, placebo-controlled study known as the HPTN 069/ACTG A5305 trial.
However, the results shouldn’t be taken as evidence of efficacy. The relatively low 2% incidence of new STIs diagnosed during 48 weeks of close followup – three cases of chlamydia, one of gonorrhea – suggests that the study population probably wasn’t at high risk for acquiring HIV. Further, the study wasn’t powered to determine efficacy. That determination will have to await a larger phase 3 trial, observed Dr. Gulick, professor of medicine at Cornell University in New York.
Maraviroc (Selzentry) is categorized as an HIV entry inhibitor. It’s an antagonist of the CCR5 receptor found on the surface of T cells, which is the route of HIV infection. The rationale for exploring the drug for HIV PrEP, according to Dr. Gulick, is that it concentrates in both the genital tract and rectum, doesn’t select for drug-resistant viral strains, is well tolerated, and it isn’t commonly used for treatment of HIV infection.
Additional options for oral daily HIV PrEP are clearly desirable, he added. The only approved agent is Truvada (tenofovir/emtricitabine), which is often used in HIV therapy as well, and there is concern it may select for drug resistance. Plus, it has renal, GI, and bone side effects.
Study participants were HIV-negative adult women who were born female and considered at risk for HIV acquisition because of a history of condomless vaginal or anal intercourse with at least one HIV-positive or unknown status man within the previous 90 days. The women were randomized to one of four study arms: maraviroc at the standard dose of 300 mg/day plus two placebo pills; maraviroc plus emtricitabine at the standard dose of 200 mg/day plus one placebo pill; maraviroc plus tenofovir at 300 mg/day plus a placebo pill, or a control regimen of fixed-dose Truvada (tenofovir 300 mg/emtricitabine 200 mg) plus two placebo pills. Thus, everyone took three pills once daily.
The three-pill regimen might help explain the less than stellar patient adherence. Study drugs were detectable – and not necessarily at therapeutic levels – in the plasma of 65% of subjects at 24 weeks and 60% at 48 weeks, with no differences between the study arms.
Maraviroc alone was associated with fewer grade 2-4 adverse events than the other regimens.
There were 11 grade 3 or 4 adverse events deemed by investigators to be related to study drugs. They included abnormal weight loss, depression, hypophosphatemia, a rise in LDL cholesterol, headache, vitamin D deficiency, back pain, two spontaneous abortions, and two dissimilar cases of congenital anomaly, with no obvious differences between the study groups in rate or pattern. Rates of specific renal and GI toxicities were comparable across the four study arms.
Earlier in 2016, Dr. Gulick presented the results of the men’s arm of HPTN 069/ACTG A5305, a parallel 48-week randomized trial in 406 men who have sex with men. Five men in the maraviroc monotherapy arm seroconverted during the 48-week study, for an incidence of 1.4%. All had no or low plasma drug concentrations, and all five were infected with HIV lacking antiretroviral drug resistance.
Dr. Gulick and coinvestigators plan to present the findings of an analysis of rectal and vaginal biopsies from 42 women in the trial, along with a bone mineral density substudy in 200 men and 200 women men in the trial, plus detailed quality-of-life, behavioral, and adherence data in the full men’s and women’s cohorts.
The trial was sponsored by the HIV Prevention Trials Network and the AIDS Clinical Trials Group with funding from the National Institute of Allergic and Infectious Diseases. Dr. Gulick reported having no financial conflicts of interest.