natgillin/translations-raw huggingface dataset:
I fase III RESIST- forsøgene var frekvensen af forhøjet transaminase signifikant forøget i APTIVUS/ ritonavir- gruppen sammenlignet med komparatorgruppen.
In Phase III RESIST trials, the frequency of transaminase elevations was significantly increased in the APTIVUS/ ritonavir arm compared to the comparator arm.
4. 4).
Close monitoring is therefore needed in patients treated with APTIVUS, co-administered with low dose ritonavir (see section 4.4).
Der foreligger på nuværende tidspunkt begrænsede data vedrørende brugen af APTIVUS givet sammen med lavdosis ritonavir til patienter, der også er smittede med hepatitis B eller C.
Limited data are currently available for the use of APTIVUS, co-administered with low dose ritonavir, in patients co-infected with hepatitis B or C.
APTIVUS bør derfor anvendes med forsigtighed til patienter, der også er smittede med hepatitis B eller C.
APTIVUS should therefore be used with caution in patients co-infected with hepatitis B or C.
APTIVUS bør kun anvendes i denne patientpopulation, hvis den potentielle fordel opvejer den potentielle risiko, og med øget klinisk monitorering og laboratoriemonitorering.
APTIVUS should be used in this patient population only if the potential benefit outweighs the potential risk, and with increased clinical and laboratory monitoring.
13 Tipranavir givet sammen med lavdosis ritonavir er undersøgt hos i alt6308 HIV- positive voksne som kombinationsbehandling i kliniske forsøg, inklusive medfølgende forsøg.
Tipranavir, co-administered with low dose ritonavir has been studied in a total of 6308 HIV-positive adults as combination therapy in clinical studies, including compassionate use studies.
Af disse fik 5219 patienter en dosis på 500 mg/ 200 mg to gange daglig.
Of these 5219 patients received the dose of 500 mg/ 200 mg twice daily.
Heraf har 909 voksne i kliniske forsøg inkl.
909 adults in clinical trials, including 541 in
541 i de to fase III forsøg (pivotal studier), RESIST- 1 og RESIST- 2 været behandlet med 500 mg/ 200 mg to gange dagligt i mindst 48 uger.
14 the RESIST-1 and RESIST-2 Phase III pivotal trials, have been treated with 500 mg/ 200 mg twice daily for at least 48 weeks.
De følgende kliniske sikkerhedsforhold (hepatotosicitet, hyperlipidæmi, blødninger, udslæt) forekom hyppigere blandt patienter behandlet med APTIVUS/ ritonavir sammenlignet med patienterne i komparatorgruppen i RESIST- forsøgene, eller er observeret ved indgivelse af APTIVUS/ ritonavir.
The following clinical safety features (hepatotoxicity, hyperlipidaemia, bleeding events, rash) were seen at higher frequency among APTIVUS/ ritonavir treated patients when compared with the comparator arm treated patients in the RESIST trials, or have been observed with APTIVUS/ ritonavir administration.
Hepatotoksicitet:
Hepatotoxicity:
Efter 48 ugers opfølgning var frekvensen af ALAT og/ eller ASAT abnormaliteter på niveau 3 eller 4 højere hos APTIVUS/ ritonavir- patienter i forhold til komparatorgruppens patienter (henholdsvis 10% og 3, 4%).
After 48 weeks of follow-up, the frequency of Grade 3 or 4 ALAT and/ or ASAT abnormalities was higher in APTIVUS/ ritonavir patients compared with comparator arm patients (10% and 3.4%, respectively).
Multivariat analyser viste, at ALAT eller ASAT ved baseline over DAIDS Grad 1, og smittede med hepatitis B eller C var risikofaktorer for disse forhøjelser.
Multivariate analyses showed that baseline ALAT or ASAT above DAIDS Grade 1 and co-infection with hepatitis B or C were risk factors for these elevations.
De fleste patienter var i stand til at fortsætte behandlingen med APTIVUS/ ritonavir.
Most patients were able to continue treatment with APTIVUS/ ritonavir.
Hyperlipidæmi:
Hyperlipidaemia:
Niveau 3 - eller 4- forhøjelser af triglycerider forekom hyppigere i APTIVUS/ ritonavir - gruppen i forhold til komparatorgruppen.
Grade 3 or 4 elevations of triglycerides occurred more frequently in the APTIVUS/ ritonavir arm compared with the comparator arm.
Ved 48 uger var tallene 25, 2% for patienterne i APTIVUS/ ritonavir- gruppen og 15, 6% i komparatorgruppen.
At 48 weeks these rates were 25.2% of patients in the APTIVUS/ ritonavir arm and 15.6% in the comparator arm.
Ved 24 uger var den relative risiko 1, 98 (95% CI=1, 03; 3, 80).
RESIST participants receiving APTIVUS/ ritonavir tended to have an increased risk of bleeding; at 24 weeks the relative risk was 1.98 (95% CI=1.03, 3.80).
Signifikansen af dette fund undersøges nærmere.
The significance of this finding is being further studied.
Der er ikke set noget unormalt mønster ved hæmatologiske eller koagualationsparametre hos patienter i al almindelighed, ej heller forudgående for udvikling af ICH.
No pattern of abnormal haematological or coagulation parameters has been observed in patients in general, or preceding the development of ICH.
Et interaktionsforsøg med kvinder mellem APTIVUS givet sammen med lavdosis ritonavir og ethinyl østradiol/ norethindron viste stor hyppighed af ikke- alvorligt udslæt.
An interaction study in women between APTIVUS, co-administered with low dose ritonavir, and ethinyl oestradiol/ norethindrone demonstrated a high frequency of non-serious rash.
4. 4).
12.5%, respectively; see section 4.4).
Der er ikke rapporteret tilfælde af Stevens- Johnsons syndrom eller toksisk epidermal nekrolyse i det kliniske udviklingsprogram for APTIVUS.
No cases of Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis have been reported in the clinical development programme of APTIVUS.
De hyppigste bivirkninger af nogen intensitet (niveau 1- 4) rapporteret i de kliniske forsøg i fase III i APTIVUS/ ritonavir- grupperne (n=749) er anført herunder efter systemorganklasse og frekvens i henhold til de følgende kategorier:
The most frequent adverse reactions of any intensity (Grades 1-4) reported in the Phase III clinical studies in the APTIVUS/ ritonavir arms (n=749) are listed below by system organ class and frequency according to the following categories:
(≥1/ 100, < 1/ 10)
Very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10)
Almindelig: hovedpine
Common: headache.
Meget almindelig: diaré, kvalme Almindelig: opkast, flatulens, abdominal udspiling, mavesmerter, løs afføring, dyspepsi
Common: vomiting, flatulence, abdominal distension, abdominal pain, loose stools, dyspepsia.
14 Hud og subkutane væv:
Skin and subcutaneous tissue disorders:
Almindelig: udslæt, pruritus
Common: rash, pruritus.
Metabolisme og ernæring:
15 Metabolism and nutrition disorders:
Almindelig: hypertriglyceridæmi, hyperlipidæmi, anoreksi
Common: hypertriglyceridaemia, hyperlipidaemia, anorexia.
Almene symptomer:
General disorders and administration site conditions:
Almindelig: træthed
Common: fatigue.
Klinisk betydningsfulde bivirkninger af moderat til svær intensitet som forekommer hos mindre end 1% (< 1/ 100) af de voksne patienter i fase II - og fase III- forsøgene, hvor der blev behandlet med 500 mg/ 200 mg tipranavir/ ritonavir- dosis (n=1397), vises nedenfor opdelt på systemorganklasser og frekvens som angivet her:
Clinically meaningful adverse reactions of moderate to severe intensity occurring in less than 1% (< 1/ 100) of adult patients in all Phase II and III trials treated with the 500 mg/ 200 mg tipranavir/ ritonavir dose (n=1397) are listed below by system organ class and frequency according to the following categories:
(≥1/ 1. 000, < 1/ 100), sjælden:
Uncommon (≥ 1/ 1,000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1,000)
(≥1/ 10. 000, < 1/ 1. 000) Undersøgelser:
Investigations:
Ikke almindelig: forhøjede leverenzymer (ALAT, ASAT), forhøjet lipase, abnorm leverfunktionstest (ALAT, ASAT), nedsat vægt
Uncommon: hepatic enzymes increased (ALAT, ASAT), lipase increased, liver function test abnormal (ALAT, ASAT), weight decreased.
Ikke almindelig: anæmi, neutropenia, trombocytopeni
Uncommon: anaemia, neutropenia, thrombocytopenia.
Ikke almindelig: svimmelhed, perifer neuropati, somnolens
Uncommon: dizziness, neuropathy peripheral, somnolence.
Ikke almindelig: dyspnø
Uncommon: dyspnoea.
Ikke almindelig: gastroøsofageal reflukssygdom, pankreatitis
Uncommon: gastrooesophageal reflux disease, pancreatitis.
Ikke almindelig: nyreinsufficiens
Uncommon: renal insufficiency.
Ikke almindelig: exanthem, lipoatrofi, erhvervet lipodystrofi, lipohypertrofi
Uncommon: exanthem, lipoatrophy, lipodystrophy acquired, lipohypertrophy.
Ikke almindelig: muskelkramper, myalgi
Uncommon: muscle cramp, myalgia.
Ikke almindelig: nedsat appetit, diabetes mellitus, hyperamylasæmi, hyperkolesterolæmi Sjælden: dehydrering, tab af fedt i ansigtet, hyperglykæmi
Rare: dehydration, facial wasting, hyperglycaemia.
Ikke almindelig: influenzalignende sygdom, utilpashed, pyreksi
Uncommon: influenza like illness, malaise, pyrexia.
Ikke almindelig: hypersensitivitet
Uncommon: hypersensitivity.
Ikke almindelig: cytolytisk hepatitis, fedtlever, hepatitis, toksisk hepatitis Sjælden: leversvigt (herunder med fatalt resultat), hyperbilirubinæmi
Rare: hepatic failure (including fatal outcome), hyperbilirubinaemia.
Ikke almindelig: søvnløshed, søvnforstyrrelser
Uncommon: insomnia, sleep disorder.
15 Laboratoriemæssige abnormiteter
Laboratory abnormalities
Frekvensen af væsentlige kliniske laboratoriemæssige abnormiteter (niveau 3 eller 4) rapporteret hos mindst 2% af patienterne i APTIVUS/ ritonavir armen i fase III kliniske forsøg (RESIST- 1 og RESIST- 2) efter 48 uger var forhøjet ASAT (6, 1%), forhøjet ALAT (9, 7%), forhøjet amylase (6, 0%), forhøjet kolesterol (4, 2%), forhøjet triglycerider (24, 9%) og fald i hvide blodlegemer (5, 7%).
16 Frequencies of marked clinical laboratory abnormalities (Grade 3 or 4) reported in at least 2% of patients in the APTIVUS/ ritonavir arms in the phase III clinical studies (RESIST-1 and RESIST-2) after 48-weeks were increased ASAT (6.1%), increased ALAT (9.7%), increased amylase (6.0%), increased cholesterol (4.2%), increased triglycerides (24.9%), and decreased white blood cell count (5.7%).
Antiretroviral kombinationsbehandling, herunder regimer indeholdende en proteasehæmmer forbindes med omfordeling af legemsfedt hos nogle patienter inkl. tab af perifert, subkutant fedt, øget intraabdominal fedt, brysthypertrofi og dorsocervikal fedtophobning ("buffalo hump").
Combination antiretroviral therapy, including regimens containing a protease inhibitor, is associated with redistribution of body fat in some patients, including loss of peripheral subcutaneous fat, increased intra-abdominal fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Proteasehæmmere forbindes også med metaboliske abnormiteter som f. eks. hypertriglyceridæmi, hyperkolesterolæmi, insulinresistens og hyperglykæmi.
Protease inhibitors are also associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance and hyperglycaemia.
Forhøjet CPK, myalgi, myositis og – i sjældne tilfælde – rhabdomyolyse er rapporteret ved behandling med proteasehæmmere, især kombineret med nukleosid reverse transcriptase- hæmmere.
Increased CPK, myalgia, myositis and, rarely, rhabdomyolysis, have been reported with protease inhibitors, particularly in combination with nucleoside reverse transcriptase inhibitors.
4. 4).
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
Reaktivering af herpes simplex og herpes zoster- virusinfektioner blev observeret i RESIST- forsøgene.
Reactivation of herpes simplex and herpes zoster virus infections were observed in the RESIST trials.
4. 4).
The frequency of this is unknown (see section 4.4).
Der findes ingen kendt antidot i tilfælde af overdosering med APTIVUS.
There is no known antidote for APTIVUS overdose.
Behandling af en overdosis bør bestå af generelle, støttende foranstaltninger inkl. monitorering af vitale parametre og observation af patientens kliniske status.
Treatment of overdose should consist of general supportive measures, including monitoring of vital signs and observation of the patient ’ s clinical status.
Indgift af aktivt kul kan også være til hjælp ved fjernelse af uabsorberet lægemiddel.
Administration of activated charcoal may also be used to aid in removal of unabsorbed drug.
Da tipranavir er stærkt proteinbundet, er det usandsynligt, at dialyse i væsentlig grad kan hjælpe med at fjerne denne medicin.
Since tipranavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of this medicine.
Antiviralt til systemisk brug, ATC- kode:
Pharmacotherapeutic group: protease inhibitor, ATC code:
Virkningsmåde:
Mechanism of action:
Humane ImmunodeFicency Virus (HIV- 1) omkoder en aspartylprotease, som er essentiel for spaltning og modning af forstadier for virusprotein.
The human immunodeficiency virus (HIV-1) encodes an aspartyl protease that is essential for the cleavage and maturation of viral protein precursors.
Tipranavir er en non- peptid- inhibitor af det HIV- 1- protease, som hæmmer viral replikation ved at forhindre modning af viralpartikler.
Tipranavir is a non-peptidic inhibitor of the HIV-1 protease that inhibits viral replication by preventing the maturation of viral particles.
Antiviral aktivitet in vitro:
Antiviral activity in vitro:
0, 07 – 0, 18 µM (42- 108 ng/ ml).
Tipranavir inhibits the replication of laboratory strains of HIV-1 and clinical isolates in acute models of T-cell infection, with 50% and 90% effective concentrations (EC50 and EC90) ranging from 0.03 to 0.07 µM (18-42 ng/ ml) and 0.07 to 0.18 µM (42-108 ng/ ml), respectively.
Tipranavir viser antiviral aktivitet in vitro mod en bred vifte af HIV- 1 gruppe M ikke- indkapslede B - isolater (A, C, D, F, G, H, CRF01 AE, CRF02 AG, CRF12 BF).
Tipranavir demonstrates antiviral activity in vitro against a broad panel of HIV-1 group M non-clade B isolates (A, C, D, F, G, H, CRF01 AE, CRF02 AG, CRF12 BF).
Gruppe O og HIV- 2 isolater viser nedsat modtagelighed in vitro over for tipranavir med EC50 værdier i intervaller på henholdsvis 0, 164 - 1 µM og 0, 233- 0, 522 µM.
Group O and HIV-2 isolates have reduced susceptibility in vitro to tipranavir with EC50 values ranging from 0.164-1 µM and 0.233- 0.522 µM, respectively.
Proteinbindingsforsøg har vist, at den antivirale aktivitet af tipranavir falder gennemsnitligt 3, 75 gange ved tilstedeværelse af humant serum.
Protein binding studies have shown that the antiviral activity of tipranavir decreases on average 3.75-fold in conditions where human serum is present.
Resistens:
Resistance:
Uviklingen af resistens over for tipranavir in vitro er langsom og kompleks.
The development of resistance to tipranavir in vitro is slow and complex.
I et bestemt in vitro resistensforsøg blev der efter 9 måneder isoleret tHIV- 1isolat, som var 87 gange resistent over for tipranavir, hvor det indeholdt 10 mutationer i proteasen:
In one particular in vitro resistance experiment, an HIV-1 isolate that was 87-fold resistant to tipranavir was selected after 9 months, and contained 10 mutations in the protease:
L10F, I13V, V32I, L33F, M36I, K45I,
L10F, I13V, V32I, L33F, M36I, K45I,
16 I54V/ T, A71V, V82L, I84V samt en mutation på gag- polyprotein CA/ P2- spaltningsstedet.
17 I54V/ T, A71V, V82L, I84V as well as a mutation in the gag polyprotein CA/ P2 cleavage site.
Reverse genetiske forsøg viste, at det var nødvendigt med tilstedeværelsen af 6 mutationer i proteasen (I13V, V32I, L33F, K45I, V82L, I84V) for at øge resistensen over for tipranavir > 10 gange, mens 10 - mutationsgenotypen øgede resistensen over for tipranavir 69 gange.
Reverse genetic experiments showed that the presence of 6 mutations in the protease (I13V, V32I, L33F, K45I, V82L, I84V) was required to confer > 10-fold resistance to tipranavir while the full 10-mutation genotype conferred 69-fold resistance to tipranavir.
In vitro er der en omvendt korrelation mellem graden af resistens over for tipranavir og kapaciteten af de vira, der repliceres.
In vitro, there is an inverse correlation between the degree of resistance to tipranavir and the capacity of viruses to replicate.
Rekombinante vira der udviser ≥3 gange resistens over for tipranavir vokser med mindre end 1% af den hastighed, der er påvist for vildtype HIV- 1 under samme betingelser.
Recombinant viruses showing ≥ 3-fold resistance to tipranavir grow at less than 1% of the rate detected for wild type HIV-1 in the same conditions.
Tipranavir- resistente vira, som frembringes in vitro ud fra vildtype HIV- 1, viser nedsat følsomhed over for proteasehæmmerne amprenavir, atazanavir, indinavir, lopinavir, nelfinavir og ritonavir, men forbliver følsomme over for saquinavir.
Tipranavir resistant viruses which emerge in vitro from wild-type HIV-1 show decreased susceptibility to the protease inhibitors amprenavir, atazanavir, indinavir, lopinavir, nelfinavir and ritonavir but remain sensitive to saquinavir.
Ved baseline og under behandlingen i kliniske forsøg har man gennem en serie multiple, trinvise regressionsanalyser af genotyper sat 16 aminosyrer i forbindelse med nedsat tipranavir- følsomhed og/ eller nedsat 48- ugers viralt belastningsrespons:
Through a series of multiple stepwise regression analyses of baseline and on-treatment genotypes from all clinical studies, 16 amino acids have been associated with reduced tipranavir susceptibility and/ or reduced 48-week viral load response:
10V, 13V, 20M/ R/ V, 33F, 35G, 36I, 43T, 46L, 47V, 54A/ M/ V, 58E, 69K, 74P, 82L/ T, 83D og 84V.
10V, 13V, 20M/ R/ V, 33F, 35G, 36I, 43T, 46L, 47V, 54A/ M/ V, 58E, 69K, 74P, 82L/ T, 83D and 84V.
Kliniske isolater som viste et ≥ 10- gange fald i følsomheden overfor tipranavir, havde 8 eller mere tipranavir- associerede mutationer.
Clinical isolates that exhibited a ≥ 10-fold decrease in tipranavir susceptibility harboured eight or more tipranavir-associated mutations.
I kliniske fase II og III forsøg viste 276 patienter at de mest almindelige mutationer ved APTIVUS- behandling er L33F/ I/ V, V82T/ L og I84V.
In Phase II and III clinical trials, 276 patients with on-treatment genotypes have demonstrated that the predominant emerging mutations with APTIVUS treatment are L33F/ I/ V, V82T/ L and I84V.
Mutationer i position 82 sker via to pathways: en fra allerede eksisterende mutation 82A, der ændrer sig til 82T, og den anden fra vildtype 82V, der ændrer sig til 82L.
Mutations at position 82 occur via two pathways: one from pre-existing mutation 82A selecting to 82T, the other from wild type 82V selecting to 82L.
Krydsresistens:
Cross-resistance:
Tipranavir forbliver signifikant, antiviralt (< 4 gange resistens) over for størstedelen af HIV- 1- kliniske isolater, som udviser nedsat følsomhed over for de godkendte proteasehæmmere: amprenavir, atazanavir, indinavir, lopinavir, ritonavir, nelfinavir og saquinavir.
Tipranavir maintains significant antiviral activity (< 4-fold resistance) against the majority of HIV-1 clinical isolates showing post-treatment decreased susceptibility to the currently approved protease inhibitors: amprenavir, atazanavir, indinavir, lopinavir, ritonavir, nelfinavir and saquinavir.
En nedsat følsomhed på > 10 gange over for tipranavir er usædvanlig (< 2, 5% af de testede isolater) i vira fra patienter, der er behandlet med flere regimer, indeholdende adskillige peptidiske proteasehæmmere.
Greater than 10-fold resistance to tipranavir is uncommon (< 2.5% of tested isolates) in viruses obtained from highly treatment experienced patients who have received multiple peptidic protease inhibitors.
Kliniske farmakodynamiske data:
Clinical pharmacodynamic data:
De præsenterede kliniske data er 48 ugers data fra igangværende forsøg (RESIST- 1 og RESIST- 2), der måler effekt på plasma- HIV- niveau og CD4 celletal.
The following clinical data is derived from analyses of 48-week data from ongoing studies (RESIST-1 and RESIST-2) measuring effects on plasma HIV RNA levels and CD4 cell counts.
RESIST- 1 og RESIST- 2 er igangværende, randomiserede, ublindede multicenterforsøg med HIV- positive, tidligere triple- behandlede patienter, der vurderer behandling med APTIVUS givet sammen med lavdosis ritonavir (500 mg/ 200 mg to gange daglig) plus en optimeret baggrundsbehandling, der defineres individuelt for hver enkelt patient ud fra genotypisk resistens- test og patientens anamnese.
RESIST-1 and RESIST-2 are ongoing, randomised, open-label, multicentre studies in HIV-positive, triple-class experienced patients, evaluating treatment with APTIVUS co-administered with low dose ritonavir (500 mg/ 200 mg twice daily) plus an optimised background regimen (OBR) individually defined for each patient based on genotypic resistance testing and patient history.
Komparatorbehandlingen omfattede en ritonavir- boostet proteasehæmmer (også defineret for hver enkelt) plus en optimeret baggrundsbehandling.
The comparator regimen included a ritonavir-boosted PI (also individually defined) plus an OBR.
Den ritonavir- boostede proteasehæmmer blev valgt blandt saquinavir, amprenavir, indinavir og lopinavir/ ritonavir.
The ritonavir-boosted PI was chosen from among saquinavir, amprenavir, indinavir or lopinavir/ ritonavir.
Efter uge 8 havde patienter i komparatorgruppen, som opfyldte protokollens kriterier om initialt manglende virologisk respons, mulighed for at ophøre med behandlingen og skifte over til APTIVUS/ ritonavir i et særskilt forsøg.
After Week 8, patients in the comparator arm who met the protocol defined criteria of initial lack of virologic response had the option of discontinuing treatment and switching over to APTIVUS/ ritonavir in a separate roll-over study.
De 1483 patienter, som indgik i den primære analyse, havde en mean alder på 43 år (interval 17- 80 år), 86% var mænd, 75% var hvide, 13% var sorte og 1% var asiatiske.
The 1483 patients included in the primary analysis had a median age of 43 years (range 17-80), were 86% male, 75% white, 13% black and 1% Asian.
4, 79 og 4, 80 log10 partikler/ ml (interval 2, 34 – 6, 52 og 2, 01 - 6, 76 log10 partikler/ ml).
In the APTIVUS and comparator arms median baseline CD4 cell counts were 158 and 166 cells/ mm3, respectively, (ranges 1-1893 and 1-1184 cells/ mm3); median baseline plasma HIV-1 RNA was 4.79 and 4.80 log10 copies/ ml, respectively (ranges 2.34-6.52 and 2.01-6.76 log10 copies/ ml).
Patienterne havde forudgående været behandlet med en median af 6 NRTI' er, 1 NNRTI og 4 PI' er.
Patients had prior exposure to a median of 6 NRTIs, 1 NNRTI, and 4 PIs.
I begge forsøg var i alt 67% patientvira resistente, og 22% var muligvis resistente over for på forhånd udvalgte komparator- proteasehæmmere.
In both studies, a total of 67% patient viruses were resistant and 22% were possibly resistant to the pre-selected comparator PIs.
17 herunder en median af 3 primære proteasegenmutationer D30N, L33F/ L, V461/ L, G48V, I50V, V82A/ F/ T/ L, I84V og L90M.
Patients had baseline HIV-1 isolates with a median of 16 HIV-1 protease gene mutations, including a median of 3 primary protease gene mutations D30N, L33F/ I, V46I/ L, G48V, I50V, V82A/ F/ T/ L, I84V, and L90M.
Hvad angår mutationer på kodon 33, 82, 84 og 90, havde ca.
With respect to mutations on codons 33, 82, 84 and 90 approximately 4% had no mutations, 24% had mutations at
4% ingen mutationer, 24% havde mutationer på kodon 82 (mindre end 1% af patienterne havde mutationen V82L) og 90, 18% havde mutationer på kodon 84 og 90, og 53% havde mindst en nøglemutation på kodon 90.
18 codons 82 (less than 1% of patients had the mutation V82L) and 90, 18% had mutations at codons 84 and 90 and 53% had at least one key mutation at codon 90.
En patient i APTIVUS- gruppen havde fire mutationer.
One patient in the APTIVUS arm had four mutations.
Desuden havde størstedelen af deltagerne mutationer i tilknytning til både NRTI - og NNRTI- resistens.
In addition the majority of participants had mutations associated with both NRTI and NNRTI resistance.