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Understanding the Details of HIV Treatment

Part One of Three in Project Inform's "What You Should Know About When to Start and What Meds to Use" Booklet

July 2011

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The START Study

Understanding the Details of HIV Treament

So far, there have not been any results from randomized, controlled studies to guide decisions about when to start treatment above 350 CD4s. Such a study has been a topic of much debate, and only recently has one gotten off the ground, appropriately named START (Strategic Timing of Anti­Retroviral Treatment). This study will enroll nearly 4,000 people in about 30 countries.

In START, people will either begin treatment with CD4s above 500 or wait until their CD4s fall to below 350. The study will assess whether people are more or less likely to result in a serious AIDS condition, other health condition or death at various CD4 levels. Sub-studies will also be done to collect information on issues such as inflammation, neurological problems, and bone, heart and liver health.

The final results are expected around 2014, with interim reports probably presented before then. Researchers expect the study to provide a clearer understanding of both the benefits and risks of starting treatment at different CD4 counts, especially long-term side effects and drug resistance.


Classes of HIV Meds

Your first regimen will probably include three drugs from two different classes. These classes work against different steps in the life cycle of HIV, so using at least two classes together reduces the risk that HIV will become resistant. Combining meds in this way will provide better and longer-lasting health outcomes.

Below is the current list of HIV meds, organized by class and then listed alphabetically by brand name, along with their generic names, three-letter abbreviations, and year of FDA approval. Some drugs are no longer used or not used often in the US, while others are used only in special circumstances.

NRTIs

Emtriva (FTC, emtricitabine, 2003)
Epivir (3TC, lamivudine, 1995)
Retrovir (AZT, zidovudine, 1987)
Videx EC (ddI, didanosine, 2004)
Viread (TDF, tenofovir, 2001)
Zerit (d4T, stavudine, 1994)
Ziagen (ABV, abacavir, 1998)

Protease Inhibitors

Aptivus (tipranavir, 2005)
Crixivan (indinavir, 1996)
Invirase (saquinavir, 2003)
Kaletra (lopinavir/r, 2000)
Lexiva (fosamprenavir, 2003)
Norvir (ritonavir, 1996)
Prezista (darunavir, 2006)
Reyataz (atazanavir, 2003)
Viracept (nelfinavir, 1997)

 

NNRTIs

Edurant (rilpivirine, 2011)
Intelence (etravirine, 2008)
Rescriptor (delavirdine, 1997)
Sustiva (EFV, efavirenz, 1998)
Viramune (nevirapine, 1996)

Entry Inhibitors

Fuzeon (T20, enfuvirtide, 2003)
Selzentry (maraviroc, 2007)

Integrase Inhibitors (INIs)

Isentress (raltegravir, 2007)

Fixed Dose Combos

Atripla (TDF+FTC+EFV, 2006)
Combivir (AZT+3TC, 1997)
Epzicom (3TC+ABV, 2004)
Trizivir (AZT+3TC+ABV, 2000)
Truvada (FTC+TDF, 2004)


A Brief Overview of the Five Classes of HIV Drugs

NRTIs

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This class is currently used as the "backbone" of most HIV regimens, and two are normally taken with one drug from another class. One combo pill, Truvada, is a preferred choice in the Guidelines. Two others, Epzicom and Combivir, are alternatives. Regimens with three NRTIs but no other drug class are not recommended, and there's not enough data yet about regimens without NRTIs

Viread (also in Truvada, Atripla) may cause kidney problems and bone loss in some people. These are somewhat uncommon but they may be serious when they do occur. Ziagen (also in Epzicom, Trizivir) can cause a serious allergic reaction in a few people, for which an HLA test can predict your risk. Ziagen may also increase the risk of heart attacks, but studies so far show conflicting results. Retrovir (also in Combivir, Trizivir) causes more fat loss in the face than other first line NRTIs. Zerit and Videx cause more side effects and are not routinely used in first line treatment.

Three NRTIs are also active against hepatitis B: Viread, Epivir and Emtriva. It's important to know whether or not you have hepatitis B before starting these HIV meds.

NNRTIs

In first line regimens, one NNRTI is usually used with two NRTIs. A person would never use two or more NNRTIs together. The Guidelines list Sustiva (also in Atripla) as a preferred choice. Many report neurological side effects such as vivid or disturbing dreams, insomnia, difficulty concentrating, mood changes and lack of concentration. People in drug recovery may not want to use Sustiva. Pregnant women (especially during first trimester) and women trying to get pregnant should not take Sustiva due to possible birth defects.

Viramune may be considered instead of Sustiva, mainly for pregnant women and people who wish to save PIs or INIs for later but are concerned about Sustiva's side effects. Viramune is listed as an alternative, due to its risk of serious liver toxicity in people at higher CD4s. It should not be started in women with >250 CD4s or in men with >400 CD4s. The risk for rash appears to be slightly higher in women than men, and it's more likely to be severe.

Edurant is approved only for people new to treatment and is less potent as Sustiva when started at viral loads above 100,000.

Intelence has not been well studied in first line regimens and should not be used if there are no signs of NNRTI resistance. Rescriptor is rarely used due to its lower potency and difficult dosing.

Protease Inhibitors

This class contains some of the most potent HIV drugs available, and HIV is less likely to become resistant compared to NNRTIs. Most PIs are boosted with a small dose of Norvir. Some doctors prefer to save PIs in case other less complicated regimens fail. However, there aren't enough studies that prove PIs are the best choice.

The Guidelines list Reyataz and Prezista as preferred PIs, while Kaletra is preferred for pregnant women. Four others are listed as alternatives. Aptivus is not used unless a person's HIV is already resistant to other PIs. Crixivan and Viracept are rarely used.

As a class, PIs tend to cause gastrointestinal problems like nausea and diarrhea. They also tend to affect metabolism. Over time, you may see changes in your cholesterol, triglycerides or blood sugar. People with heart disease or diabetes may want to save PIs for their second or third regimens. For pregnant women, PIs may not fully suppress HIV, especially during the third trimester, so the dose may need to be adjusted.

Entry Inhibitors

In some cases, Selzentry may be used in first line treatment, but in studies it didn't match the potency of Sustiva. The Guidelines state that there is not enough evidence to recommend Selzentry. A tropism test must be done before using it. Fuzeon is given as an injection twice a day, which is challenging for individuals. It has not been studied as a first line regimen.

Integrase Inhibitors

Isentress is a preferred option for first line therapy. We don't yet know enough about its long-term side effects, although it's generally well tolerated and is proving to be a potent HIV drug.

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This article was provided by Project Inform. Visit Project Inform's website to find out more about their activities, publications and services.
 
See Also
"What You Should Know About When to Start and What Meds to Use": Table of Contents
Part Two: Your Ability to Start and Maintain
Part Three: Getting Ready to Start HIV Treatment

 

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