As you may know, the monthly injectable medication – Cabenueva, has been offered at the Doc Shop for more than a year. We know that every two months would be easier than coming into the office once monthly. But, we do not currently recommend it for every two months. The studies have shown that the medicine dosed every 8 weeks fails more often than every 4 weeks.
A total of 1045 people with HIV were treated for 152 weeks with either: A) Cabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly (400/600 mg) as 2- 2cc shots monthly orB) Cabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly (600/900 mg) as 2- 3cc shots every 2 months
The hope was these two dosing regimens would be the same. The study used a calculation to determine, not that the study protocols were the same or equivalent; but that every 2 month dosing (B) is statistically non-inferior (not worse than) the monthly dosing (A). This type of trial has potential flaws, most importantly how the non-inferiority number is chosen. In this case it was set at 4%. That means one arm of the trial is considered “non-inferior” to the other if the difference between the outcomes is less than 4% (4 in each 100).
Results: Group A (4 wks) Group B (8 wks)Number of people 523 522Failures (HIV broke through) 5 14
The study was reported out as meeting the 4% noninferiority threshold because statistically the 2.7% (Group B- 14 people of 522) failure rate is not inferior (less than 4%) of the 1% (Group A- 5 people of 523) failure rate.
Of the two arms of the trial which would you rather be in? Note that more than twice the number of people failed treatment during the 152 weeks of the trial if they were dosed every 8 rather than every 4 weeks. Most who experienced treatment failure developed evidence of resistance to Rilpivirine.
Also:The medicine disappears from the blood at a mean concentration to ½ dose at 5.6-11.5 weeks for the CAB and 13-28 weeks for the RPV.
Mean concentrations of the RPV show it stays in the body longer than the CAB. That means RPV may be the only drug in the system if someone either doesn’t come in time for their dose or if someone metabolizes the medication quickly. During the decades we have studied HIV, we learned that one medicine is not enough to control HIV. If the RPV stands alone, it likely will not control the virus. RPV resistance will be more likely to develop (which can mean the entire class of integrase inhibitor medicines is useless).
OpinionWhile the concept is being tweaked, it is my opinion that the injectable dosing of Cabenueva/Rilpivirine once every 4 weeks is safer for most patients than once every 8 weeks.
Diagnosis, Treatment & Prevention of HIV
This study is not definitive. But it did show the use of 200 mg of doxycycline after exposure (post-exposure prophylaxis or PEP) within at most 72 hours after unprotected sex reduced the overall incidence of STIs. The study included 554 Men who have sex with men. Infections occurred in 10.3% of doxy recipients and 29% of the placebo group. Protection appeared to work best for gonorrhea, followed by chlamydia and syphilis.