AIDS InfoNet Logo
This website is certified by Health On the Net Foundation. Click to verify.
This site complies with the HONcode standard for trustworthy health information:
verify here.

The Henry J. Kaiser Family Foundation
Site of the Week
November 2003

The Health Leader Award 2006
The Health Leader Award 2006

The HOPE Reward Medical Award Featured Site Award

IBS Tales Hope Award Editor's Choice Award

Listed in Listed in Treasures of the Internet

AIDS InfoNet Logo.  The AIDS InfoNet - Reliable, Up-to-Date AIDS Treatment Information
International Association of Providers of AIDS Care
Revised September 26, 2014

Fact Sheet 105

How HIV Drugs Get Approved



Developing a new drug can take 10 years or more. First, drug companies must find substances that are active against HIV. Most HIV drugs are identified by testing existing drugs for anti-HIV activity (screening). A newer method is rational drug design. In this process, scientists “build” drug molecules to fight HIV in specific ways.

When a promising drug is identified, it goes through pre-clinical testing. This involves test-tube and animal studies. These show whether the drug works against HIV and how it works. They also show how it can be manufactured, and make sure it is not too toxic (poisonous).

If pre-clinical results are good enough, the drug company files an Investigational New Drug (IND) application. Then it starts testing the drug in humans (clinical trials). Only about 1 candidate drug in 1,000 makes it into clinical trials. When enough clinical trials are completed, the manufacturer submits an NDA, or New Drug Application. If the FDA approves the NDA, the drug can be sold to treat specific medical conditions.



There are four phases of human clinical trials. These apply to all drugs, not just drugs for HIV/AIDS. If the results from any phase of testing are not good enough, the company will stop developing the drug.

Phase I trials test the safety of new drugs for humans. These trials record the side effects that occur at different dosages of the drug. Everyone in a Phase I trial receives the new drug, but different participants may get different dosages. The trials usually study less than 100 people, and take less than a year. In Phase I trials, new drugs are given to humans for the first time. People who participate in Phase I trials face the highest risks compared to possible benefits.

Phase II trials can enroll several hundred people and take 1 to 2 years. They study what does of drug may work best against HIV. They also collect more information about side effects. Only about 1 drug candidate in 3 makes it through Phase II trials.

These trials are usually randomized. This means that trial participants are divided into two groups that are similar in terms of age, sex, and health. One group receives the study drug. The other group is the reference or control group. People in the control group get standard treatment (called “standard of care”). If there is no standard treatment, they may get a dummy medication (called a placebo).

In some trials, neither the participants or their health care providers know who is getting the study drug or the placebo. This is called a blinded study. Studies are blinded so that the health care providers will be totally objective when they evaluate the health of patients in the study.

Phase III trials collect more data on a drug’s effectiveness and side effects, using the dose selected in the phase II study. These trials can study up to a few thousand people and often last for two years or more.

Phase III trials are normally randomized and blinded. Participants might not receive the study drug. With good results in Phase III trials, a manufacturer can apply for FDA approval to sell the new drug.

Phase IV trials are called “post-marketing studies.” Phase IV trials can monitor a new drug’s long-term effectiveness and side effects in new combinations, or how cost-effective it is. They can also compare the new drug to other drugs approved for the same condition.



The FDA used to require trials that measured clinical endpoints before approving a new HIV drug. These trials analyze how many people get sicker, develop opportunistic infections, or die.

However, these trials take a long time and are very expensive. A faster, cheaper way to test new drugs is by using indirect measures of patient health. These surrogate markers are laboratory values such as viral load or CD4 cell counts. The FDA approved the use of surrogate markers for full approval of new HIV drugs.

Clinical trials should include people like those who will use the drug. But manufacturers sometimes prefer to test their products in people who are as healthy as possible. For example, sometimes they exclude people infected with hepatitis B or C because of their liver problems, although many people with HIV also are infected with hepatitis.



There are three legal ways to use drugs that the FDA has not approved to treat a specific health problem:

1. Expanded Access is a program where manufacturers provide unapproved drugs to people who cannot take part in a clinical trial. Patients must meet conditions set by the drug manufacturer. The drugs are usually offered at no charge, but participating health care providers have to collect information on how patients respond to the drug.

2. Treatment IND Protocol or Compassionate Use. The FDA can allow drug companies to provide new drugs to people who are very ill and who have no other treatment options. A related type of access is called Parallel Track. This policy was developed to provide investigational drugs to people with AIDS who are unable to participate in clinical trials of those drugs.

3. Off-label use. Health care providers can write a prescription for any FDA-approved drug, even to use it for some medical condition it was not approved for. This is called off-label use. There may be no information about how often medications are used off-label, or how well they work. 




The FDA Center for Drug Evaluation and Research has an informative Internet web page:

The AIDSinfo clinical trials search ( provides information on clinical trials that are currently enrolling participants.



Back to Fact Sheet Categories

International Association of Providers of AIDS Care


The AIDS InfoNet is a project of the International Association of Providers of AIDS Care.


United States National Library of Medicine

Partially funded by the National Library of Medicine

Search Our Site
Newest Fact Sheets
Print This Fact Sheet
You can print this fact sheet on a single page in Microsoft Word (.doc) format or Adobe Acrobat (.pdf) format. Click on the links below to open the document in your browser and then print it.
 Adobe Acrobat PDF
 Microsoft Word

You can print directly from your browser using the link below. The printout will probably go onto a second page.
 Print Version (Web)

Monthly E-mail Updates

The InfoNet updates its Fact Sheets frequently. A listing of each month's changes is posted to several e-mail lists.

If you would like to receive this monthly update by personal e-mail, please click on the SUBMIT button.