New drug regimen/new choices after 17 years

[Guest guest]

Even though it has worked well since 1994, my doc wants to change my meds. He

gave me printouts on Truvada (tenofovir + emtricitabine), Efavirenz(sustiva),

Atazanavir (reyataz), and Raltegravir (isentress).

I'd appreciate opinions from those taking or having tried any of these to help

make me decision. I have been taking indinivir/combivir/acyclovir.

Dave

[Guest guest]

daveYou forgot to say:1- what are you taking now and what have you taken in the past

2- Your genotype test results

On Tue, Jan 25, 2011 at 12:40 PM, presh911 <dpal911@...> wrote:

Even though it has worked well since 1994, my doc wants to change my meds.  He gave me printouts on Truvada (tenofovir + emtricitabine), Efavirenz(sustiva), Atazanavir (reyataz), and Raltegravir (isentress).

I'd appreciate opinions from those taking or having tried any of these to help make me decision.  I have been taking indinivir/combivir/acyclovir.

Dave

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[Guest guest]

Are there any articles / medical recommendations that explain why someone would want to switch cocktails? I know some of the really older meds, after along time are not too good for you (but what is??) - but i'm of the school of thought that "if it ain't broke - don't fix it"

Even though it has worked well since 1994, my doc wants to change my meds. He gave me printouts on Truvada (tenofovir + emtricitabine), Efavirenz(sustiva), Atazanavir (reyataz), and Raltegravir (isentress).

I'd appreciate opinions from those taking or having tried any of these to help make me decision. I have been taking indinivir/combivir/acyclovir.

Dave

------------------------------------

[Guest guest]

Beside failure other reasons for changing medicationsgo from intolerable side effects like Diarrhea, pancreatitisetc.. to more Lypo friendly combination to reduce or eliminatelypodistropy and atrophy, reduce cholesterol or to limit toxicity, allergies to medications are another reason believe or not this can happen even after some one has taken the same medication for a long time.It is very common for HIV+ patients to develop allergies to sulfa base

drugs. Life quality is another reason, some medications work better then others with some people life style, I guess this would be more about choosing what kind of side effects one can live with and how often medications are taken during the day.But I would guess the best reason for some one to switch to a new regime even when not needed is because the new regime is more effectiveand the doctor is trying to further improve that patient condition. Mark BFrom: "deleriium@..." <deleriium@...>presh911 <dpal911@...>; Vergel <Vergel@...>Cc: Sent: Thu, January 27, 2011 9:43:52 AMSubject: Re:

New drug regimen/new choices after 17 years

Are there any articles / medical recommendations that explain why someone would want to switch cocktails? I know some of the really older meds, after along time are not too good for you (but what is??) - but i'm of the school of thought that "if it ain't broke - don't fix it"

Even though it has worked well since 1994, my doc wants to change my meds. He gave me printouts on Truvada (tenofovir + emtricitabine), Efavirenz(sustiva), Atazanavir (reyataz), and Raltegravir (isentress).

I'd appreciate opinions from those taking or having tried any of these to help make me decision. I have been taking indinivir/combivir/acyclovir.

Dave

------------------------------------

[Guest guest]

The Federal HIV treatment guidelines (which and Jeff of this list

helped develope) include a good discussion of reasons for a treatment

experienced patient to consider switching regimens, which regimens patients and

their doctors should consider changing from, and regimens that they can switch

to.

I disagree with your " if it ain't broke, don't fix it " school of thought,

particularly when it comes to persons on treatment regimens with significant

toxicities or side effects, or difficult dosing requirements. It is better to

change regimens before there is virologic resistance, and newer ARV medications

often have lower toxicities, side effects and easier dosing schedules. You can

usually change back to a previously effective regimen if the new one doesn't

work out.

See page 77-80 of the guidelines:

http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf

REGIMEN SIMPLIFICATION (Updated January 10, 2011)

Regimen simplification can be defined broadly as a change in established

effective therapy to reduce pill burden and dosing frequency, to enhance

tolerability, or to decrease specific food and fluid requirements. Many patients

on suppressive antiretroviral therapy (ART) may be considered candidates for

regimen simplification, especially if (1) they are receiving treatments that are

no longer recommended as preferred or alternative choices for initial therapy;

(2) they were prescribed a regimen in the setting of treatment failure at a time

when there was an incomplete understanding of resistance or drug-drug

interaction data; or (3) they were prescribed a regimen prior to the

availability of newer options or formulations that might be easier to administer

and/or more tolerable.

This section will review situations in which clinicians might consider

simplifying treatment in a patient with virologic suppression. Importantly, this

section will not review consideration of changes in treatment for reducing

ongoing adverse effects. Regimens used in simplification strategies generally

should be those that have proven high efficacy in antiretroviral (ARV)-naïve

patients (see What to Start) or that would be predicted to be highly active for

a given patient based on the individual’s past treatment history and

resistance profile.

Rationale

The major rationales behind regimen simplification are to improve the

patient’s quality of life, maintain long-term adherence, avoid toxicities that

may develop with prolonged ARV use, and reduce the risk of virologic failure.

Systematic reviews in the non-HIV literature have shown that adherence is

inversely related to the number of daily doses [1]. Some prospective studies in

HIV-infected individuals have shown that those on regimens with reduced dosing

frequency have higher levels of adherence [2-3]. Patient satisfaction with

regimens that contain fewer pills and reduced dosing frequency is also higher

[4].

Candidates for Regimen Simplification

Unlike ARV agents developed earlier in the HIV epidemic, many ARV medications

approved in recent years have sufficiently long half-lives to allow for

once-daily dosing, and most also do not have dietary restrictions. Patients on

regimens initiated earlier in the era of potent combination ART with drugs that

pose a high pill burden and/or frequent dosing requirements are often good

candidates for regimen simplification.

Patients without suspected drug-resistant virus. Patients on first (or modified)

treatment regimens without a history of treatment failure are ideal candidates

for regimen simplification. These patients are less likely to harbor

drug-resistant virus, especially if a pretreatment genotype did not detect drug

resistance. Prospective clinical studies have demonstrated that the likelihood

of treatment failure is relatively low in patients after simplification and,

indeed, may be lower than in patients who do not simplify treatment [5].

However, some patients may have unrecognized drug-resistant HIV, either acquired

at the time of infection or as a consequence of prior treatment, such as

patients who were treated with presumably nonsuppressive mono- or

dual-nucleoside reverse transcriptase inhibitor (NRTI) regimens before the

widespread availability of HIV RNA monitoring and resistance testing.

Patients with documented or suspected drug resistance. Treatment simplification

may also be appropriate for selected individuals who achieve viral suppression

after having had documented or suspected drug resistance. Often, these patients

are on regimens selected when management of drug resistance, understanding of

potentially adverse drug-drug interactions, and understanding of treatment

options were relatively limited. Regimen simplification may also be considered

for patients on two ritonavir (RTV)-boosted protease inhibitors (PIs). Although

successful in suppressing viral replication, this treatment may cause patients

to be on regimens that are cumbersome, costly, and associated with potential

long-term adverse events. The ability to simplify regimens in this setting often

reflects the availability of recently approved agents that have activity against

drug-resistant virus and are easier to take without sacrificing ARV activity.

Specific situations in which drug simplification could be considered in

ART-experienced patients with viral drug resistance are outlined below.

Simplifying regimens in patients who have extensive prior treatment histories is

complicated. In such a case, a patient’s treatment history, treatment

responses and tolerance, and resistance test results should be thoroughly

reviewed before designing a new regimen. Expert consultation should be

considered whenever possible.

January 10, 2011

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and

Adolescents Page 78

Types of Treatment Simplification

Within-Class Simplifications. Within-class substitutions offer the advantage of

not exposing patients to still-unused drug classes, which potentially preserves

other classes for future regimens. In general, within-class substitutions use a

newer agent; coformulated drugs; or a formulation that has a lower pill burden,

a lower dosing frequency, or would be less likely to cause toxicity.

• NRTI Substitutions (e.g., changing from zidovudine [ZDV] or stavudine [d4T]

to tenofovir [TDF] or abacavir [ABC]): This may be considered for a patient who

has no history of viral resistance on an NRTI-containing regimen. Other NRTIs

may be substituted to create a regimen with lower dosing frequency (e.g., once

daily) that takes advantage of coformulated agents and potentially avoids some

long-term toxicities (e.g., pancreatitis, peripheral neuropathy, lipoatrophy).

• Switching of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) (e.g.,

from nevirapine [NVP] to efavirenz [EFV]): This may be considered to reduce

dosing frequency or to take advantage of coformulated agents.

• Switching of PIs: This switch can be from one PI to another PI, to the same

PI at a lower dosing frequency (such as from twice-daily to once-daily

RTV-boosted lopinavir [LPV/r] or RTV-boosted darunavir [DRV/r]) or, in the case

of atazanavir (ATV), to administration without RTV boosting [6]. (Unboosted ATV

is presently not a preferred PI component and not recommended if the patient is

taking TDF or if the patient has HIV with reduced susceptibility to ATV.) Such

changes can reduce dosing frequency, pill count, drug-drug or drug-food

interactions, or dyslipidemia or can take advantage of coformulation. These

switches can be done with relative ease in patients without PI-resistant virus.

However, these switches are not recommended in patients who have a history of

documented or suspected PI resistance because convincing data in this setting

are lacking.

Out-of-Class Substitutions. One common out-of-class substitution for regimen

simplification involves a change from a PI-based to an NNRTI-based regimen. An

important study in this regard was the NEFA trial, which evaluated substitution

of a PI-based regimen in virologically suppressed patients with NVP, EFV, or ABC

[7]. Although the baseline regimens in the study are no longer in widespread

use, the NEFA findings are still relevant and provide information about the

risks and benefits of switching treatment in patients with virologic

suppression. In this study, 460 patients on stable, PI-based regimens with

virologic suppression (<200 copies/mL for the previous 6 months) were switched

to their randomized treatment arms. After 36 months of follow-up, virologic

failure occurred more frequently in patients switched to ABC than in patients

switched to EFV or NVP. The increased risk of treatment failure was particularly

high in patients who had previous suboptimal treatment with mono- and dual-NRTI

therapy. This emphasizes the need to consider the potential for drug-resistant

virus prior to attempting simplification [8].

Newer agents that target different sites in the HIV life cycle, such as the

integrase strand transfer inhibitor (INSTI) raltegravir (RAL) and the CCR5

antagonist maraviroc (MVC), also offer opportunities for out-of-class

substitutions, particularly in patients who have a history of virus resistant to

older HIV drugs. Three randomized studies have evaluated replacing a boosted PI

with RAL in virologically suppressed patients. In two of these studies [9-10],

the switch to RAL was associated with an increased risk of virologic failure in

patients with documented or suspected pre-existing NRTI resistance; a third

study did not find this higher risk, possibly due to a longer period of

virologic suppression before the change [11]. Overall, these results suggest

that in ART-experienced patients, RAL should be used with caution as a

substitute for a boosted PI. This strategy should be avoided in patients with

documented NRTI resistance unless there are other fully active drugs in the

regimen.

Because enfuvirtide (T-20) requires twice-daily injections, causes

injection-site reactions, and is more expensive than other available ARV agents,

patients who are virologically suppressed on T-20-containing regimens may wish

to substitute T-20 with an active oral agent. Because the majority of patients

on T-20 have highly drug-resistant virus, substitution must be with another

fully active agent. Data from one randomized trial and one observational study

suggest that RAL can safely substitute for T-20 in patients not previously

treated with INSTI [12-13]. Although this strategy generally maintains virologic

suppression and is well tolerated, clinicians should be aware that any drug

substitution may introduce unanticipated adverse effects or drug-drug

interactions [14].

Other newer agents that might be considered as substitutes for T-20 are

etravirine (ETR) or MVC. Use of ETR in this setting would optimally be

considered only when viral susceptibility to ETR can be assured from resistance

testing performed prior to virologic suppression and after carefully assessing

for possible deleterious drug-drug interactions

January 10, 2011

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and

Adolescents Page 79

(e.g., ETR cannot be administered with several PIs [see Table 16b]). In the ETR

early access program, switching from T-20 to ETR showed promise in maintaining

viral suppression at 24 weeks, but only 37 subjects were included in this report

[15]. MVC is only active in those with documented R5-only virus, a determination

that cannot routinely be made in those with undetectable HIV RNA on a stable

regimen. Although there is a commercially available proviral DNA assay to assess

viral tropism in virologically suppressed patients, there are no clinical data

on whether results of this test predict the successful use of MVC as a

substitute for another active drug.

Reducing the number of active drugs in a regimen. This approach to treatment

simplification involves switching a patient from a suppressive regimen to fewer

active drugs. In early studies, this approach was associated with a higher risk

of treatment failure than continuation of standard treatment with two NRTIs plus

a PI [16]. More recently, studies have evaluated the use of an RTV-boosted PI as

monotherapy after virologic suppression with a two-NRTI + boosted-PI regimen

[17-18]. The major motivations for this approach are a reduction in NRTI-related

toxicity and lower cost. In a randomized clinical trial [18], low-level viremia

was more common in those on maintenance LPV/r alone than on a three-drug

combination regimen. Viral suppression was achieved by resuming the NRTIs.

Studies of DRV/r monotherapy, both as once- or twice-daily dosing, have reported

mixed results [19-20]. In aggregate, boosted-PI monotherapy as initial [21] or

as simplification treatment has been somewhat less effective in achieving

complete virologic suppression and avoiding resistance. Therefore, this strategy

cannot be recommended outside of a clinical trial.

Monitoring After Treatment Simplification

Patients should be evaluated 2†" 6 weeks after treatment simplification to

assess tolerance and to undergo laboratory monitoring, including HIV RNA, CD4

cell count, and markers of renal and liver function. Assessment of fasting

cholesterol subsets and triglycerides should be performed within 3 months after

the change in therapy. In the absence of any specific complaints, laboratory

abnormalities, or viral rebound at that visit, patients may resume regularly

scheduled clinical and laboratory monitoring.

References

1. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations

between dose regimens and medication compliance. Clin Ther.

2001;23(8):1296-1310.

2. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and

efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med.

2006;354(3):251-260.

3. Molina JM, Podsadecki TJ, MA, et al. A lopinavir/ritonavir-based

once-daily regimen results in better compliance and is non-inferior to a

twice-daily regimen through 96 weeks. AIDS Res Hum Retroviruses.

2007;23(12):1505-1514.

4. Stone VE, Jordan J, Tolson J, et al. Perspectives on adherence and simplicity

for HIV-infected patients on antiretroviral therapy: self-report of the relative

importance of multiple attributes of highly active antiretroviral therapy

(HAART) regimens in predicting adherence. J Acquir Immune Defic Syndr.

2004;36(3):808-816.

5. Gatell J, Salmon-Ceron D, Lazzarin A, et al. Efficacy and safety of

atazanavir-based highly active antiretroviral therapy in patients with virologic

suppression switched from a stable, boosted or unboosted protease inhibitor

treatment regimen: the SWAN Study (AI424-097) 48-week results. Clin Infect Dis.

2007;44(11):1484-1492.

6. Squires KE, Young B, Dejesus E, et al. Similar efficacy and tolerability of

atazanavir compared with atazanavir/ritonavir, each with abacavir/lamivudine

after initial suppression with abacavir/lamivudine plus ritonavir-boosted

atazanavir in HIV-infected patients. AIDS. 2010;24(13):2019-2027.

7. ez E. The NEFA study: results at three years. AIDS Rev. 2007;9(1):62.

8. Ochoa de Echaguen A, Arnedo M, Xercavins M, et al. Genotypic and phenotypic

resistance patterns at virological failure in a simplification trial with

nevirapine, efavirenz or abacavir. AIDS. 2005;19(13):1385-1391.

9. Eron JJ, Young B, DA, et al. Switch to a raltegravir-based regimen

versus continuation of a lopinavir-ritonavir-based regimen in stable

HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two

multicentre, double-blind, randomised controlled trials. Lancet.

2010;375(9712):396-407.

10. Vispo E, Barreiro P, Maida I, et al. Simplification From Protease Inhibitors

to Once- or Twice-Daily Raltegravir: The ODIS Trial. HIV Clin Trials.

2010;11(4):197-204.

11. ez E, Larrousse M, Llibre JM, et al. Substitution of raltegravir for

ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL

study. AIDS. 2010;24(11):1697-1707.

12. M, Larsen G, Montaner JS. Outcomes of multidrug-resistant patients

switched from enfuvirtide to raltegravir within a virologically suppressive

regimen. AIDS. 2008;22(10):1224-1226.

13. De Castro N, Braun J, Charreau I, et al. Switch from enfuvirtide to

raltegravir in virologically suppressed multidrug-resistant HIV-1-infected

patients: a randomized open-label trial. Clin Infect Dis. 2009;49(8):1259-1267.

14. M, Larsen G, Montaner JS. Exacerbation of depression associated with

starting raltegravir: a report of four cases. AIDS. 2008;22(14):1890-1892.

January 10, 2011

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and

Adolescents Page 80

15. Loutfy M, Ribera E, Florence E, et al. Sustained HIV RNA suppression after

switching from enfuvirtide to etravirine in the early access programme. J

Antimicrob Chemother. 2009;64(6):1341-1344.

16. Havlir DV, Marschner IC, Hirsch MS, et al. Maintenance antiretroviral

therapies in HIV infected patients with undetectable plasma HIV RNA after

triple-drug therapy. AIDS Clinical Trials Group Study 343 Team. N Engl J Med.

1998;339(18):1261-1268.

17. Swindells S, DiRienzo AG, Wilkin T, et al. Regimen simplification to

atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained

virologic suppression. JAMA. 2006;296(7):806-814.

18. Pulido F, Arribas JR, Delgado R, et al. Lopinavir-ritonavir monotherapy

versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV.

AIDS. 2008;22(2):F1-9.

19. Arribas JR, Horban A, Gerstoft J, et al. The MONET trial:

darunavir/ritonavir with or without nucleoside analogues, for patients with HIV

RNA below 50 copies/ml. AIDS. 2010;24(2):223-230.

20. Katlama C, Valantin MA, Algarte-Genin M, et al. Efficacy of

darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral

suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136.

AIDS. 2010;24(15):2365-2374.

21. Delfraissy JF, Flandre P, Delaugerre C, et al. Lopinavir/ritonavir

monotherapy or plus zidovudine and lamivudine in antiretroviral-naive

HIV-infected patients. AIDS. 2008;22(3):385-393.

>

>

> Even though it has worked well since 1994, my doc wants to change my meds.

 He gave me printouts on Truvada (tenofovir + emtricitabine),

Efavirenz(sustiva), Atazanavir (reyataz), and Raltegravir (isentress).

>

> I'd appreciate opinions from those taking or having tried any of these to help

make me decision.  I have been taking indinivir/combivir/acyclovir.

>

> Dave

>

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[Guest guest]

"I disagree with your "if it ain't broke, don't fix it" school of thought, particularly when it comes to persons on treatment regimens with significant toxicities or side effects, or difficult dosing requirements"To me, if someone has significant toxicities, or emerging viral resistance, "it's broke," so I don't think we disagree.I would probably like to be on an integrase-based regimen, but ever since my body adapted to new Norvir, it's not a pressing issue.JB