Combination Medications

• What Are Combination Medications?
• What Are PK Boosters?

1. Combinations of Reverse Transcriptase Inhibitors ("Nukes")
2. Combinations of a Non-Nucleoside Reverse Transcriptase Inhibitor and Reverse Transcriptase Inhibitors
3. Combinations of Protease Inhibitors
4. Other Combinations in Development

What Are Combination Medications?

Combination medications are pills or tablets that contain more than one medication to fight HIV. They are listed in the tables below. Pharmaceutical companies have been working hard to make their medications easier to take. Part of this effort has been to combine more than one medication in a single pill. These combinations are referred to as fixed-dose combinations, or FDCs.

The first FDC to treat HIV was Combivir by ViiV Healthcare. Combivir contains two nucleoside analog reverse transcriptase inhibitors. This was followed by Trizivir, also by ViiV Healthcare, which includes 3 nukes. Some antiviral products are only available outside the US through the US President's Emergency Plan for AIDS Relief (PEPFAR.) For more information, see Fact Sheet 475 or www.pepfar.gov.

Be sure that you do not take a combination medication along with any of its components! For example, do not take Truvada with tenofovir (Viread) or emtricitabine (Emtriva); do not take Combivir along with zidovudine (Retrovir) or lamivudine (Epivir.)

What Are PK Boosters?

When some medications are taken by mouth, their levels in the blood are very low. For them to fight HIV, they have to be taken at high doses. Another possibility is to "boost" their blood levels. This is done by slowing down the processing (metabolism) of these drugs. A drug that slows down the metabolism is called a "PK booster." PK stands for pharmacokinetic. This refers to the way that medications are processed by the body.

The first PK booster used in HIV was ritonavir by Abbott. Ritonavir slows down the metabolism of many drugs by the liver. This increases the blood levels of some anti-HIV medications so that a lower dose can be taken. However, it can also increase blood levels of many other drugs. In some cases, this can cause a harmful overdose.

A second PK booster by Gilead Sciences, cobicistat (GS-9350), is in Phase III trials. Other PK boosters in Phase I trials include PF-03716539 by ViiV Healthcare, SPI-452 by Sequoia, and TMC558445 by Tibotec Pharmaceuticals.

1. Combinations of Reverse Transcriptase Inhibitors ("Nukes")

Year Approved*	Generic Name	Trade Name	Also Known As:	Manufacturer
1997	Zidovudine/lamivudine	Combivir	AZT or ZDV, 3TC	ViiV Healthcare & generic
2000	Zidovudine/lamivudine/abacavir	Trizivir	AZT or ZDV, 3TC, ABC	ViiV Healthcare & generic
2004	Abacavir/lamivudine	Epzicom	ABC, 3TC	ViiV Healthcare & generic
2004	Emtricitabine/tenofovir	Truvada	Emtriva and Viread	Gilead Sciences & generic
At present, the following combinations are only available outside the US due to patent protections for the original developers
2007	Lamivudine/stavudine		3TC, d4T	Generic
2008	Lamivudine/tenofovir		3TC, TDF	Generic

2. Combinations of a Non-Nucleoside Reverse Transcriptase Inhibitor and Reverse Transcriptase Inhibitors

Year Approved*	Generic Name	Trade Name	Also Known As:	Manufacturer
2006	Efavirenz/emtricitabine/tenofovir	Atripla	EFV, Emtriva, & TDF	Bristol-Myers Squibb and Gilead
2011	Emtricitabine/rilpivirine/tenofovir	Complera	Emtriva, Edurant and Viread	Gilead and Tibotec
At present, the following combinations are only available outside the US due to patent protections for the original developers
2005	Nevirapine/zidovudine/lamivudine	Duovir	NVP, AZT or ZDV, 3TC	Generic
2006	Efavirenz/zidovudine/lamivudine		EFV, AZT or ZDV, 3TC	Generic
2006	Nevirapine/lamivudine/stavudine	Triomune	NVP, 3TC, d4T	Generic
2006	Efavirenz/lamivudine/stavudine		EFV, 3TC, d4T	Generic
2010	Nevirapine/lamivudine/stavudine		NVP, 3TC, d4T	Generic

3. Combinations of Protease Inhibitors

NOTE: a small dose of ritonavir is used to boost blood levels of other protease inhibitors. The amount of ritonavir is not high enough to fight HIV.

Year Approved*	Generic Name	Trade Name	Also Known As:	Manufacturer
2000	Lopinavir/ritonavir	Kaletra, Aluvia	LPV/r	Abbott & generic

4. Other Combinations in Development

Gilead Sciences is studying a combination of elvitegravir (integrase inhibitor); emtricitabine and tenofovir (nukes) with cobicistat (GS9350), a PK booster. This "quad" pill would be a full anti-HIV medication regimen in just one pill per day. Gilead and Tibotec are developing a combination of darunavir and cobicistat. It would be taken as a single tablet once a day.

* Year of approval of the first version of the combination. More information on medications approved as part of the US President's Emergency Plan for AIDS Relief is available at www.fda.gov/oia/pepfar.htm.