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Two Triple PEP Regimens With Truvada Look Safer Than Older PEPs
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5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
Two postexposure prophylaxis (PEP) combinations for occupational or nonoccupational HIV exposure--Truvada plus raltegravir and Truvada plus lopinavir/ritonavir--proved generally safer and more tolerable than older PEP combos studied by the same investigators [1,2].
PEP with Truvada (tenofovir/emtricitabine) plus raltegravir makes more intuitive sense than Truvada plus lopinavir/ritonavir because all three drugs in the first regimen block HIV before viral integration with cellular DNA, while the protease inhibitors (PIs) lopinavir/ritonavir stop HIV after it has already entered cells and integrated with their DNA. Also, raltegravir appears to have fewer side effects than lopinavir/ritonavir, and tolerability is an important consideration when concocting PEP medleys. At least in women, raltegravir penetrates the genital tract well [3].
Kenneth Mayer and colleagues evaluated Truvada/raltegravir at Boston's Fenway Institute, the largest New England health center caring for gay men, more than 1000 of whom have HIV infection [1]. The Fenway group has studied nonoccupational PEP since 1997. Their earlier work established the safety and tolerability of PEP with tenofovir plus either emtricitabine or lamivudine [4].
Starting in March 2008, Mayer and coworkers evaluated once-daily Truvada and twice-daily raltegravir in 51 men and compared results with those in 199 people at the center who had tried PEP earlier with zidovudine/lamivudine plus a PI . Age averaged 34 years and ranged from 20 to 61 in the Truvada/raltegravir group. Forty-five men (88%) were white, and 45 had a college degree.
Forty-nine men identified themselves as gay or bisexual, but all 51 listed sex with another man as their reason for wanting PEP. Thirty men knew their sex partner had HIV infection, 28 had insertive anal sex with no condom or a condom that broke, and 27 had receptive anal sex with no condom or one that broke. About two thirds of men reported receptive oral sex without a condom. Three quarters of the men drank alcohol before sex and many used marijuana, poppers, cocaine, Viagra, crystal meth, and/or Ecstasy.
Compared with the 119 people who used zidovudine/lamivudine plus a PI as PEP, the Truvada/raltegravir group reported significantly less diarrhea (29.4% versus 58.8%), nausea or vomiting (31.4% versus 58.8%), and fatigue (9.8% versus 48.5%), but significantly more abdominal discomfort, pain, gas, or bloating (17.6% versus 2.9%) (P < 0.01 for all comparisons). While 58.5% of men taking Truvada/raltegravir completed their PEP course, 38.8% completed the PI PEP regimen (P < 0.01). Only 2 men stopped Truvada/raltegravir because of side effects. More than 90% of men reported at least 90% adherence with the 4-week PEP regimen, and 58.5% reported 100% adherence. No one in this study became infected.
French national guidelines recommend a 4-week PEP course with two nucleosides and one boosted PI. Christian Rabaud and coworkers throughout France evaluated Truvada plus lopinavir/ritonavir tablets in a prospective observational study that began in November 2006 [2]. Of the 249 people who tried this PEP regimen, 66% were men and 34% were women. Their age averaged 31.5 years. While 204 people (82%) needed PEP after consensual sex, 5 (2%) wanted PEP after forced sex, and 40 (16%) after occupational exposure.
Twenty-seven people (11%) stopped coming back for planned visits, 27 (11%) stopped shortly after starting PEP because their sex partner had a negative HIV test or the transmission risk was judged low, 7 people (3%) stopped for reasons other than side effects, 22 people (9%) stopped because of side effects after a median of 7 days, and 166 people (67%) completed all 28 days of PEP dosing. The most commonly reported side effects were diarrhea (in 80% with side effects), weakness (in 66%), and abdominal pain (in 44%).
A significantly lower proportion of people taking this PEP melange stopped because of side effects than stopped other PEPs studied by this group:
· Truvada/lopinavir/ritonavir (tablet): 22 (11.7%) stopped, 166 (88.3%) did not stop
· Tenofovir/lamivudine/atazanavir/ritonavir: 22 (21.0%) stopped, 83 (79.0%) did not (P = 0.03 versus Truvada/lopinavir/ritonavir)
· Zidovudine/lamivudine/lopinavir/ritonavir (soft gel): 25 (22.5%) stopped, 85 (77.5%) did not (P = 0.001 versus Truvada/lopinavir/ritonavir)
· Zidovudine/lamivudine/nelfinavir: 53 (34.5%) stopped, 101 (65.5%) did not (P < 0.0001 versus Truvada/lopinavir/ritonavir)
A higher proportion of people taking Truvada/lopinavir/ritonavir reported good versus poor tolerability (51% versus 49%) than did so with tenofovir/lamivudine/atazanavir/ritonavir (44.5% versus 55.5%, nonsignificantly different Truvada/lopinavir, P = 0.49), zidovudine/lamivudine/lopinavir/ritonavir (soft gel) (41% versus 59%, nonsignificant, P = 0.18), or zidovudine/lamivudine/nelfinavir (20% versus 80%, significant, P < 0.0001).
One person taking Truvada plus lopinavir/ritonavir had grade 4 creatine phosphokinase elevations and rhabdomyolysis (rapid muscle tissue breakdown). Three people had grade 3 alanine aminotransferase elevations, and 3 had grade 3 hypophosphatemia.
References
1. Mayer K, Mimiaga M, Gelman M, et al. Tenofovir DF/emtricitabine/raltegravir appears safe and well-tolerated for non-occupational post-exposure prophylaxis. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract WEAC104.
2. Tosini W, Muller P, Prazuck T, et al. Tolerability of post-exposure prophylaxis (PEP) of HIV infection with the combination of tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation (Truvada + Kaletra). 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract WEAC102.
3. Jones A, Talameh J, Patterson K, Rezk N, Prince H, Kashuba A. First-dose and steady-state pharmacokinetics (PK) of raltegravir (RAL) in the genital tract (GT) of HIV uninfected women. 10th International Workshop on Clinical Pharmacology of HIV Therapy, April 15-17, 2009, Amsterdam. Abstract O_06.
4. Mayer KH, Mimiaga MJ, Cohen D, et al. Tenofovir DF plus lamivudine or emtricitabine for nonoccupational postexposure prophylaxis (NPEP) in a Boston Community Health Center. J Acquir Immune Defic Syndr. 2008;47:494-499.
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