what is salvage therapy in the context of hiv treatment?

Salvage therapy, in this context, is the attempt to contain the replicating HIV once the usual line of treatments have been exhausted. When at least one regimen containing protease inhibitors has failed in a patient, the subsequent attempts to treat the HIV infection may be referred to as salvage therapy.

Full Answer

What is salvage therapy for HIV?

Salvage therapy for HIV will attempt to stop the spread of the resistant form of the virus. The first-line treatment for most types of cancer is chemotherapy. All chemotherapy is made from one or more drugs that have been shown to fight cancer. When standard chemotherapy isn’t working, salvage therapy can be used.

What is the most important factor in salvage therapy success?

The experience of physicians is an important factor in the success of salvage therapy.

What are the most common diseases that require salvage therapy?

The most common diseases that require salvage therapy are HIV and various cancers. The term is not clearly defined; it is used both to mean a second attempt and a final attempt.

What is Salvage chemotherapy?

Salvage chemotherapy is a treatment that is given after the cancer has not responded to other chemotherapy regimens. ^ "Definition of Salvage therapy". MedicineNet.com. 2006.

What is salvage therapy?

Listen to pronunciation. (SAL-vij THAYR-uh-pee) Treatment that is given after the cancer has not responded to other treatments.

What is salvage chemotherapy in medical terms?

Salvage chemotherapy: Chemotherapy given after recurrence of a tumor.

What are the 3 antiretroviral therapy?

They include: non-nucleoside reverse transcriptase inhibitors (NNRTIs) nucleoside reverse transcriptase inhibitors (NRTIs) post-attachment inhibitors.

What is second line therapy in HIV treatment?

Second-line Antiretroviral Therapy (ART) regimens are used when patients develop treatment failure for first-line drug regimens. It is costly unaffordable and it is not widely available for patients in resource limiting setting, there is a need to maximizing the duration of stay on second-line regimen.

What is the difference between salvage radiation and adjuvant radiation?

Two postoperative approaches to reduce risk for relapse are commonly used: Adjuvant radiotherapy (ART), which should be performed within 4 months after surgery, triggered mainly by tumor size and surgical margins, and salvage radiotherapy (SRT), which is performed when prostate-specific antigen (PSA) levels increase ...

Does salvage chemotherapy work?

Salvage chemotherapy regimens are considered to be effective based on remission rates alone. Although few studies provide survival data, those that do typically report OS in the range of 5-15 months [Thomas et al.

Which are the 5 antiretroviral drugs?

Currently, there are eight FDA-approved NRTIs: abacavir (ABC, Ziagen), didanosine (ddI, Videx), emtricitabine (FTC, Emtriva), lamivudine (3TC, Epivir), stavudine (d4T, Zerit), zalcitabine (ddC, Hivid), zidovudine (AZT, Retrovir), and Tenofovir disoprovil fumarate (TDF, Viread), a nucleotide RT inhibitor (Fig.

What are the 6 classes of antiretroviral drugs?

Classes of antiretroviral agents include the following:Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs)Protease inhibitors (PIs)Nonnucleoside reverse transcriptase inhibitors (NNRTIs)Fusion inhibitors.CCR5 co-receptor antagonists (entry inhibitors)HIV integrase strand transfer inhibitors.

What are the five goals of antiretroviral therapy?

Thus, once initiated, ART should be continued, with the following key treatment goals:Maximally and durably suppress plasma HIV RNA;Restore and preserve immunologic function;Reduce HIV-associated morbidity and prolong the duration and quality of survival; and.Prevent HIV transmission.

What is first line and second-line treatment?

Second-line treatment is treatment for a disease or condition after the initial treatment (first-line treatment) has failed, stopped working, or has side effects that aren't tolerated. It's important to understand "lines of treatment" and how they differ from first line treatment and can play a role in clinical trials.

When should I switch to the second-line of ARV?

For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 1000 copies/ml.

What is first line of treatment?

THAYR-uh-pee) The first treatment given for a disease. It is often part of a standard set of treatments, such as surgery followed by chemotherapy and radiation. When used by itself, first-line therapy is the one accepted as the best treatment.

Salvage Treatment for HIV

Note: Salvage treatment is sometimes also called “Rescue Therapy” or “Third-Line Therapy.”

Selected Recent Articles

Patients who fail modern HIV regimens show high prevalence of older mutations . (December 2016, Hepmag)

What is salvage therapy?

Salvage therapy, also known as rescue therapy, is a form of therapy given after an ailment does not respond to standard therapy. The most common diseases that require salvage therapy are HIV and various cancers. The term is not clearly defined; it is used both to mean a second attempt and a final attempt.

How do ARVs help HIV?

If the patient's viral load (the amount of HIV in the blood) rebounds after being suppressed by ARVs, the virus has likely developed resistance to the ARVs. As more and more mutations conferring drug resistance develop in the HIV's genome, it becomes difficult to select an ARV that will meaningfully suppress HIV replication and keep the patient's viral load low. Salvage therapy, in this context, is the attempt to contain the replicating HIV once the usual line of treatments have been exhausted. When at least one regimen containing protease inhibitors has failed in a patient, the subsequent attempts to treat the HIV infection may be referred to as salvage therapy.

Is salvage therapy more severe than standard therapy?

Salvage therapy drugs or drug combinations have, in general, much more severe side effects than the standard line of therapy. This is often true of a drug of last resort.

Does ARV suppress HIV replication?

As more and more mutations conferring drug resistance develop in the HIV's genome, it becomes difficult to select an ARV that will meaningfully suppress HIV replication and keep the patient's viral load low.

Why is salvage therapy so difficult to write about?

Salvage therapy is one of the most difficult topics to write about because every statement must be qualified in relation to an individual's personal treatment history. Although this should be the case with any medical decision, choices about HIV treatment should be tailored for each person.

Why interrupt therapy before starting a new salvage regimen?

These include allowing a reversion from resistant to wild-type virus, a break from side effects, and a short period to psychologically prepare to cope with a subsequent mega-HAART combination (a regimen containing five or more drugs).

Why are antiretroviral drugs not effective?

As discussed above, due to toxicity the highest tolerable dose of an antiretroviral drug may be only just above the amount needed to avoid resistance. Missing even an occasional dose can cause drug levels between doses to fall so low that the drug no longer suppresses the virus. This is a particular concern with once-daily medications, since more time passes between doses and the virus therefore has more time to replicate in the absence of an adequate concentration of the drug in the event of a missed dose. Following the dietary requirements for a medication is also important.

How to increase antiretroviral activity?

One way to increase the antiretroviral activity of a drug is to add another medication that "boosts" the blood level of the first drug. As discussed above, this works because certain medications inhibit drug metabolism in the liver.

How many drugs are needed for salvage therapy?

By definition, people who require salvage therapy do not have three potent drugs available, so regimens with larger numbers of drugs -- sometimes up to nine -- may be needed to achieve adequate potency. Even drugs that are not very potent by themselves can still contribute some antiretroviral activity to a combination.

What is the treatment history file?

It is important for people to keep their own treatment history file that includes CD4 cell count, viral load, and resistance test results, together with a list of drugs previously used, medication allergies, past side effects, and adherence levels (frequency of taking doses as prescribed).

Why does treatment fail?

Both lectures emphasized that there are only a limited number of known reasons why treatment might fail: drug resistance, inadequate drug potency, suboptimal drug levels, poor adherence, and drug toxicity.

What is the gold standard boosted PI regimen for use in salvage therapy?

The current gold standard boosted-PI regimen for use in salvage therapy and as a comparator in various studies, is lopinavir/ritonavir, which is the boosted PI for 50% of patients in the RESIST study. David Cooper 39 presented the results of a sub-analysis of the RESIST study that looked at how lopinavir/ritonavir fared when compared to tipranavir + ritonavir. Also looked at were comparisons involving whether patients who were previously taking lopinavir/ritonavir and enfuvirtide, and how enfuvirtide affected response rates. The results of the lopinavir/ritonavir versus tipranavir + ritonavir comparison are shown in the figure below. Those results demonstrate the clear superiority of the tipranavir + ritonavir arm.

What is the test for multi-drug resistant HIV?

This assay measures viral fitness, which is a gauge of how well an HIV isolate can replicate. It is believed that HIV that accumulates antiretroviral resistance mutations is less fit than wild-type HIV.

What is the compound 1 for reverse transcriptase inhibitors?

The agent, which is being called Compound-1, has a non-nucleoside structure and binds to the active site of HIV reverse transcriptase (like NNRTIs), although a translocation assay shows that this compound forces the enzyme to move on its primer-template in the same manner as when a dNTP binds the enzyme. Thus, Compound-1 appears to be somewhat of a hybrid of NRTIs and NNRTIs.

What is the agent for PI-resistant HIV?

Another agent under investigation for its activity against PI-resistant HIV is an agent now known as 640385 (also known as VX-385 or GW0385). Six possible doses given for 2 weeks +/- ritonavir were evaluated in HIV-uninfected volunteers. 44 This double-blind, randomized, placebo-controlled, repeat dose, escalating study was conduced in 6 sequential groups of HIV-uninfected participants. The arms were as follows:

What is a viral blip?

A common scenario involves a patient who has a plasma HIV-RNA level below 50 copies/mL and on a subsequent measure is noted to have a detectable viral level. If the viral load measure rises to between 50 and 500 copies/mL and then drops back down to undetectable by the next measurement , this is termed a viral blip. It is a continuing question whether this viral blip indicates early virologic failure due to resistance, sub-therapeutic drug levels, virus from reservoirs or some other explanation we haven't yet considered.

What is therapeutic drug monitoring?

In addition to resistance tests, therapeutic drug monitoring is another tool that has been utilized widely in Europe to assist in the management of virologic failure. Ferdinand Wit presented data from a substudy 10 of the 2NN study, which compared nevirapine (NVP, Viramune) to efavirenz in treatment-naive HIV-infected persons. 11 In this substudy, the researchers looked at the relationship between the plasma concentrations of nevirapine and efavirenz and virologic failure.

Is antiretroviral therapy effective?

The use of antiretroviral therapy has grown increasingly widespread, but not all regimens are created equal. Many antiretroviral combinations have less-than-optimal effectiveness, particularly those that include older, less-potent drugs. At the same time, adherence is an issue for many HIV-infected patients, particularly given the pill burden associated with many previous-generation antiretrovirals. As a result, many clinicians fear that the number of patients developing multi-drug resistance will continue to grow, leaving a steadily rising number of patients with fewer and fewer available treatment options. Fortunately, encouraging data presented at CROI suggest that the newer potent regimens, with their easier scheduling, lower pill burden and, as a result, better adherence, may actually be reducing the incidence of triple-class resistance.

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Salvage Therapy Strategies

Experience Counts

Antiretroviral drugs (ARVs) are given to slow down the HIV reproduction, which in turn increases quality of life and survival. If the patient's viral load (the amount of HIV in the blood) rebounds after being suppressed by ARVs, the virus has likely developed resistance to the ARVs. As more and more mutations conferring drug resistance develop in the HIV's genome, it becomes difficult to select an ARV that will meaningfully suppress HIV replication and keep the patient's viral load …

Summary

• Addressing the various factors that contribute to treatment failure can improve the likelihood of successful salvage therapy. Two management approaches will be discussed below: whether or not to interrupt therapy before starting a new salvage regimen, and whether there is a benefit to using multiple drugs in salvage therapy. Both approaches have be...

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