(introduction...)

· abacavir, amprenavir, delavirdine, didanosine, efavirenz, indinavir, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, zalcitabine, zidovudine, and some combinations

Two of the above antiretroviral drugs, zidovudine and nevirapine, are included in the MEDL (1999). Both drugs are included solely for use in the prevention of mother-to-child transmission (MTCT) of HIV.

Currently available antiretroviral drugs belong to two major classes of drugs: reverse transcriptase inhibitors and protease inhibitors. The first group is further divided into nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors. These drugs act by blocking the action of enzymes that are important for replication and functioning of HIV.

Many of the antiretroviral drugs are not covered by patent in all countries. As a result, a number of generic manufacturers in countries such as Argentina, India, Mexico, Republic of Korea, Spain, and Thailand are producing these drugs and exporting to other countries. However, some generic manufacturers, including many of the private Brazilian manufacturers, only supply their national market and do not yet have the capacity to export these products.

1.1 Antiretroviral drugs used in prevention of MTCT and included in MEDL (1999)

Zidovudine (ZDV, also known as AZT)

Zidovudine is a nucleoside reverse transcriptase inhibitor. It was added to the tenth MEDL solely for use in the prevention of mother-to-child transmission of HIV. However, zidovudine is also used in combination therapy to suppress the replication of HIV. Generic versions are widely available, as 100 mg and 250 mg capsules. The dosage used in prevention of MTCT is usually 300 mg. Indicative prices vary widely depending on the country of origin.

Use in HIV/AIDS: Prevention of MTCT (MEDL). Combination therapy to suppress replication of HIV.

Notes in 11^th Model list: Limited indications or narrow spectrum of activity.

- capsule, 100 mg. MEDL. Reported shelf-life: 24 to 60 months
- capsule, 250 mg. MEDL. Reported shelf-life: 48 to 60 months
- injection, 10 mg/ml in 20-ml vial. MEDL. Reported shelf-life: 12 months
- oral solution, 50 mg/5 ml. MEDL. Reported shelf-life: 18 to 24 months
- oral syrup, 10 mg/5 ml. Strength not in MEDL
- tablet, 300 mg. Not in MEDL. Used in pilot projects for prevention of MTCT. Provided as a donation by Glaxo Wellcome to a restricted number of countries.

Nevirapine (NVP)

Nevirapine is a non-nucleoside reverse transcriptase inhibitor. This drug, used in combination therapy to suppress the replication of HIV, was included in the 1991 MEDL for the same indication as zidovudine (prevention of MTCT). For this indication, a combination of tablet for the mother and syrup formulation for the newborn child is required. The indicative cost per treatment is US$ 4 from the patent holder. However, the patent holder, Boehringer Ingelheim, has recently stated that the company will make the product available for MTCT free of charge to the least developed and low-income developing countries with specific programmes for the prevention of MTCT. Countries should approach the company directly for inclusion in this donation. The donation is exclusively for use in the prevention of MTCT^* and may not be used in combination therapy to suppress the replication of HIV.

* Use of Nevirapine for the Prevention of Mother-to-Child Transmission of HIV. Technical Notes. WHO HIV/AIDS-RHR-EDM, Geneva, 2001 (WHO/HIV-AIDS/2001.3; WHO/RHR/01.21).

Use in HIV/AIDS: Prevention of MTCT (MEDL). Combination therapy to suppress replication of HIV.

Notes in 11^th Model list: Limited indications or narrow spectrum of activity.

- tablet 200 mg. MEDL.
- oral solution 50 mg/ml (240 ml). MEDL.

1.2 Antiretroviral drugs not included in MEDL (1999)

Combination antiretroviral therapies reduce plasma viral load levels and have a beneficial clinical effect. HIV-related symptoms may disappear, the incidence of opportunistic infections is reduced, and quality of life improves. However, these treatments are not a cure for AIDS and must be given for life, unless treatment fails or they are superseded by new drug combinations. For optimal efficacy, antiretroviral drugs, usually from different classes, must be used in combination. Several combination regimens with demonstrated effectiveness in achieving durable suppression of HIV replication are available. However, the current antiretroviral therapy is far from ideal. In addition to the high cost of the drugs, some regimens are complicated, all may cause severe side effects, and the treatment requires monitoring.

Like most other drugs, antiretroviral drugs are not covered by patents in all countries. They can therefore be legally produced and exported by generic manufacturers in countries where the products have not been patented, and can be legally imported and used in other countries where they have not been patented.

The mid-2000 survey of sources and prices was not very successful in obtaining data on the source and price of antiretroviral drugs. Only a few companies responded and of those several supplied incomplete information. The report only includes information from manufacturers that supplied all the information requested. Therefore, the information in Table 1. gives an incomplete picture of the present status of the international market in generic antiretrovirals. As this is a rapidly evolving field, contact information for manufacturers that supplied incomplete information will be made available to procurement officers, with a caveat that information is limited on both the quality of their products and their ability to ensure a constant supply of their products.

Abacavir

Abacavir is a nucleoside reverse transcriptase inhibitor used in combination therapy to suppress replication of HIV.

- tablet, 300 mg. Not in MEDL.
- syrup, 20 mg/ml. Not in MEDL.

Amprenavir

Amprenavir is a protease inhibitor used in combination therapy to suppress replication of HIV.

- capsule 50 mg. Not in MEDL. This drug was not included in the two surveys but will be included in future surveys.

Delavirdine

Delavirdine mesylate is a non-nucleoside reverse transcriptase inhibitor used in combination therapy to suppress replication of HIV.

- tablets, 100 and 200 mg. Not in MEDL. This drug was not included in the two surveys but will be included in future surveys.

Didanosine (ddI)

Didanosine is a nucleoside reverse transcriptase inhibitor used in combination therapy to suppress replication of HIV.

- tablet, 25 mg. Not in MEDL.
- tablet, 100 mg. Not in MEDL.
- syrup, 2 g. Not in MEDL.

Efavirenz

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used in combination therapy to suppress replication of HIV.

- capsule, 200 mg. Not in MEDL.

Indinavir

Indinavir is a protease inhibitor used in combination therapy to suppress replication of HIV.

- capsule, 400 mg. Not in MEDL.

Lamivudine (3TC)

Lamivudine is a nucleoside reverse transcriptase inhibitor used in combination therapy to suppress replication of HIV.

- tablet, 150 mg. Not in MEDL.
- syrup, 5 mg/ml. Not in MEDL.

Nelfinavir

Nelfinavir is a protease inhibitor used in combination therapy to suppress replication of HIV.

- capsule, 250 mg. Not in MEDL.

Ritonavir

Ritonavir is a protease inhibitor used in combination therapy to suppress replication of HIV.

- capsule, 100 mg. Not in MEDL. This drug was not included in the two surveys but will be included in future surveys.

Saquinavir

Saquinavir is a protease inhibitor used in combination therapy to suppress replication of HIV.

- capsule, 200 mg. Not in MEDL.

Stavudine (d4T)

Stavudine is a nucleoside reverse transcriptase inhibitor used in combination therapy to suppress replication of HIV.

- capsule, 40 mg. Not in MEDL.
- syrup, 1 mg/ml. Not in MEDL.

Zalcitabine (ddC)

Zalcitabine is a nucleoside reverse transcriptase inhibitor used in combination therapy to suppress replication of HIV.

- tablet, 0.75 mg. Not in MEDL.

Abacavir, lamivudine plus zidovudine.

Fixed dose combination product containing two different nucleoside reverse transcriptase inhibitor and a HIV-protease inhibitor.

- tablet, abacavir (as sulphate) 300 mg, lamivudine 150 mg, and zidovudine 300 mg. Not in MEDL. This drug was not included in the two surveys but will be included in future surveys.

Lopinavir plus ritonavir

This is a fixed dose combination of two HIV-protease inhibitors. The combination results in increased plasma levels of lopinavir.

- capsules, lopinavir 133.3 mg, ritonavir 33.3 mg. Not in MEDL. This drug was not included in the two surveys but will be included in future surveys.

Zidovudine plus lamivudine (ZDV/3TC)

Fixed dose combination product containing two different nucleoside reverse transcriptase inhibitors that are often used in combination with a non-nucleoside reverse transcriptase inhibitors or HIV-protease inhibitors.

- tablet, 300/150 mg. Not in MEDL.

Table 1. Sources and prices of antiretroviral drugs

ANTIVIRALS	Manuf.		Indicative prices (US$ 2000)						List Prices
Antiretrovirals	No./countries		Unit	MAX	MIN	MEDIAN	25th Perc./No.<		UK	Spain
Lamivudine (3TC)
tab, 150 mg	3	2	tab	0.43	0.14	0.29	0.21	1	3.93	2.26
syrup, 5 mg/ml	1	1	100 mls	2.99	2.99	2.99	2.99	1	-	-
Abacavir
tab, 300 mg	2	2	tab	5.32	3.61	4.47	4.04	1	5.73	3.61
syrup, 20 mg/ml	-	-	240 ml	-	-	-	-	-	91.58	57.78
Zidovudine (ZDV)
cap, 100 mg	7	7	cap	0.30	0.18	0.28	0.24	2	1.71	0.66
cap, 250 mg	4	3	cap	0.75	0.50	0.66	0.55	1	4.29	1.65
cap, 300 mg	4	4	cap	0.60	0.28	0.44	0.36	1	-	1.98
syrup, 10 mg/5 ml	-	-		-	-	-	-	-	-	-
inj, 10 mg/ml, 20 ml	-	-	vial	-	-	-	-	-		-
oral sol, 50 mg/5 ml	1	1	100 ml	2.35	2.35	2.35	2.35	1	34.37	-
Stavudine (d4T)
syrup, 1 mg/ml	-	-	200 ml	-	-	-	-	-	35.06	17.94
cap, 40 mg	4	4	cap	0.42	0.30	0.36	0.33	2	4.42	2.12
Zalcitabine
tab, 0.75 mg	-	-	tab	-	-	-	-	-	-	1.27
Didanosine (ddI)
tab,25 mg	1	1	tab	0.19	0.19	0.19	0.19	1	0.69	0.30
tab, 100 mg	2	2	tab	0.87	0.61	0.74	0.68	1	2.12	1.19
syrup, 2 g	-	-	118 ml	-	-	-	-	-	-	23.84
ZDV/3TC comb
tab, 300/150 mg	1	1	tab	No price					-	4.65
Efavirenz
cap, 200 mg	-	-	cap	-	-	-	-	-	3.59	2.76
Nevirapine
tab, 200 mg	1	1	tab	1.47	1.47	1.47	1.47	1	4.03	3.20
syrup, 50 mg/5 ml	-	-	240 ml	-	-	-	-	-	72.58	-
Indinavir
cap, 400 mg	-	-	-	-	-	-	-	-	1.64	1.40
Nelfinavir
cap, 250 mg	-	-	cap	-	-	-	-	-	1.54	1.05
Saquinavir
cap, 200 mg	-	-	cap	-	-	-	-	-	0.84	0.67

1.3 Donations and price reductions for antiretroviral drugs

In May 2000, a new initiative - Accelerating Access - was launched by the UNAIDS Co-sponsors and the Secretariat to help improve access to care and support for people living with HIV/AIDS. The initiative was established in response to an offer from five research-based pharmaceutical manufacturers to lower the price of antiretroviral drugs for use in low-income countries.

In October 2000, expressions of interest were sought from both research-based and generic pharmaceutical manufacturers who were interested in becoming potential suppliers of pharmaceutical products through the Accelerating Access initiative. The offers received include antiretrovirals, selected treatments for opportunistic infections, and diagnostics. The manufacturers involved will be subject to a pre-qualification process undertaken over the coming months.

In addition, in recent months a number of pharmaceutical manufacturers have made public announcements of their willingness to reduce the price of certain antiretroviral drugs to low-income countries in Africa, Latin America, and Asia. Annex I is a summary of both the publicly announced offers and the offers from manufacturers which responded to the call for expressions of interest. In some cases, recipients may be required to meet certain conditions in order to take up individual offers of reduced-price drugs.