Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400 copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90–125 days). The median number of past regimens was 6 (IQR, 3–8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.
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References
1.
BartlettJA, FathMJ, DemasiRet al.An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults. AIDS, 2006; 20:2051–2064.
2.
von WylV, YerlyS, BurgisserPet al.Long-term trends of HIV type 1 drug resistance prevalence among antiretroviral treatment-experienced patients in Switzerland. Clin Infect Dis, 2009; 48:979–987.
3.
YouleM, StaszweskiS, ClotetBet al.Concomitant use of an active boosted protease inhibitor with enfuvirtide in treatment-experienced, HIV-infected individuals: Recent data and consensus recommendations. HIV Clin Trials, 2006; 7:86–96.
4.
GallantJE. Protease-inhibitor boosting in the treatment-experienced patient. AIDS Rev, 2004; 6:226–233.
5.
ArnaizJA, MallolasJ, PodzamczerDet al.Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load. AIDS, 2003; 17:831–840.
6.
BoffitoM, MaitlandD, SamarasingheY, PozniakA. The pharmacokinetics of HIV protease inhibitor combinations. Curr Opin Infect Dis, 2005; 18:1–7.
7.
KempfDJ, KingMS, BernsteinBet al.Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. J Infect Dis, 2004; 189:51–60.
8.
VoigtE, WasmuthJC, VogelMet al.Safety, efficacy and development of resistance under the new protease inhibitor lopinavir/ritonavir: 48-week results. Infection, 2004; 32:82–88.
9.
HirschMS, GunthardHF, SchapiroJMet al.Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin Infect Dis J, 2008; 47:266–285.
10.
HammerSM, VaidaF, BennettKKet al.Dual vs single protease inhibitor therapy following antiretroviral treatment failure: A randomized trial. JAMA, 2002; 288:169–180.
11.
HammerSM, EronJJJr., ReissPet al.Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA, 2008; 300:555–570.
12.
RiddlerSA, HaubrichR, DiRienzoAGet al.Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med, 2008; 358:2095–2106.
13.
von WylV, YerlyS, BoniJet al.Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. Clin Infect Dis, 2008; 46:1299–1309.
14.
von WylV, YerlyS, BoniJet al.Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: A comparison of different regimen types. Arch Intern Med, 2007; 167:1782–1790.
15.
BoffitoM, DickinsonL, HillAet al.Steady-state pharmacokinetics of saquinavir hard-gel/ritonavir/fosamprenavir in HIV-1-infected patients. J Acquir Immune Defic Syndr, 2004; 37:1376–1384.
16.
BoffitoM, KurowskiM, KruseGet al.Atazanavir enhances saquinavir hard-gel concentrations in a ritonavir-boosted once-daily regimen. AIDS, 2004; 18:1291–1297.
17.
BoffitoM, MaitlandD, DickinsonLet al.Pharmacokinetics of saquinavir hard-gel/ritonavir and atazanavir when combined once daily in HIV Type 1-infected individuals administered different atazanavir doses. AIDS Res Hum Retroviruses, 2006; 22:749–756.
18.
ColomboS, BuclinT, FrancCet al.Ritonavir-boosted atazanavir-lopinavir combination: A pharmacokinetic interaction study of total, unbound plasma and cellular exposures. Antivir Ther, 2006; 11:53–62.
19.
JohnsonM, GrinsztejnB, RodriguezCet al.Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS, 2005; 19:685–694.
20.
RiberaE, AzuajeC, LopezRMet al.Atazanavir and lopinavir/ritonavir: Pharmacokinetics, safety and efficacy of a promising double-boosted protease inhibitor regimen. AIDS, 2006; 20:1131–1139.
21.
RiberaE, LopezRM, DiazMet al.Steady-state pharmacokinetics of a double-boosting regimen of saquinavir soft gel plus lopinavir plus minidose ritonavir in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother, 2004; 48:4256–4262.
22.
WalmsleyS, BernsteinB, KingMet al.Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med, 2002; 346:2039–2046.
23.
GilliamBL, Chan–TackKM, QaqishRB, RodeRA, FantryLE, RedfieldRR. Successful treatment with atazanavir and lopinavir/ritonavir combination therapy in protease inhibitor-susceptible and protease inhibitor-resistant HIV-infected patients. AIDS Patient Care STDS, 2006; 20:745–759.
24.
HammerSM, SaagMS, SchechterMet al.Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society–USA panel. Top HIV Med, 2006; 14:827–843.
25.
CollierAC, TierneyC, DowneyGFet al.Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV. HIV Clin Trials, 2008; 9:91–102.
26.
GuptaR, HillA, SawyerAW, PillayD. Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: A systematic review of clinical trials. Clin Infect Dis, 2008; 47:712–722.
27.
HosseinipourM. Resistance profile of patients failing first line ART in Malawi when using clinical and immunologic monitoring. Paper presented at: Seventeenth International AIDS Conference, 2008Mexico City.
28.
Gupta RHA, SawyerA, Cozzi–LepriAet al.The intensity of virological monitoring is associated with resistance to first line HAART in HIV-1 infected adults under the WHO public health approach to antiretroviral therapy: A systematic analysis of cohort and trial data. Lancet Infect Dis, 2009; 9:409–417.
29.
LedergerberB, von OverbeckJ, EggerM, LuthyR. The Swiss HIV Cohort Study: Rationale, organization and selected baseline characteristics. Soz Praventivmed, 1994; 39:387–394.
30.
SudreP, RickenbachM, TaffeP, JaninP, VolkartAC, FrancioliP. Clinical epidemiology, research on HIV infection in Switzerland: The Swiss HIV Cohort Study 1988–2000. Schweiz Med Wochenschr, 2000; 130:1493–1500.
31.
GrinsztejnB, VelosoVG, PilottoJH, CamposDP, KerulyJC, MooreRD. Comparison of clinical response to initial highly active antiretroviral therapy in the patients in clinical care in the United States and Brazil. J Acquir Immune Defic Syndr, 2007; 45:515–520.
32.
GrinsztejnB, NguyenBY, KatlamaCet al.Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: A phase II randomised controlled trial. Lancet, 2007; 369:1261–1269.
33.
MadrugaJV, CahnP, GrinsztejnBet al.Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet, 2007; 370:29–38.
34.
MolinaJM, CohenC, KatlamaCet al.Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24-week results of POWER 3. J Acquir Immune Defic Syndr, 2007; 46:24–31.
35.
CorbettAH, EronJJ, FiscusSA, RezkNL, KashubaAD. The pharmacokinetics, safety, and initial virologic response of a triple-protease inhibitor salvage regimen containing amprenavir, saquinavir, and ritonavir. J Acquir Immune Defic Syndr, 2004; 36:921–928.
36.
la PorteCJ, WasmuthJC, SchneiderK, RockstrohJK, BurgerDM. Lopinavir/ritonavir plus saquinavir in salvage therapy; pharmacokinetics, tolerability and efficacy. AIDS, 2003; 17:1700–1702.
37.
SmithGH, BoulasselMR, KlienMet al.Virologic and immunologic response to a boosted double-protease inhibitor-based therapy in highly pretreated HIV-1-infected patients. HIV Clin Trials, 2005; 6:63–72.
PetersenML, WangY, van der LaanMJ, RheeSY, ShaferRW, FesselWJ. Virologic efficacy of boosted double versus boosted single protease inhibitor therapy. AIDS, 2007; 21:1547–1554.
40.
LoutfyM, RaboudJ, ThompsonCet al.Clinical impact of double protease inhibitor boosting with lopinavir/ritonavir and amprenavir as part of salvage antiretroviral therapy. HIV Clin Trials, 2003; 4:301–310.
41.
KosalaraksaP, BunupuradahT, EngchanilCet al.Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks. Pediatr Infect Dis J, 2008; 27:623–628.
42.
AnanworanichJ, KosalaraksaP, HillAet al.Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children. Pediatr Infect Dis J, 2005; 24:874–879.
GlassTR, De GeestS, HirschelBet al.Self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predicts treatment failure in virologically suppressed patients. Antivir Ther, 2008; 13:77–85.
45.
BoniJ, PyraH, GebhardtMet al.High frequency of non-B subtypes in newly diagnosed HIV-1 infections in Switzerland. J Acquir Immune Defic Syndr, 1999; 22:174–179.
