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HIV Treatment and the Nonclinician: Getting Your Bearings

This past August, Ryan White Comprehensive AIDS Resources Emergency (CARE) Act-funded grantees and providers gathered in Washington, DC, for the biennial All-Titles Technical Assistance Meeting. Veterans of previous All-Titles conferences noted a significant increase in the number of young professionals participating in the 2006 event, and registration data showed that an incredible 46 percent of approximately 2,300 registrants were attending an All-Titles conference for the first time.

It is not known what proportion of the attendees are new to the field of HIV/AIDS services. Nevertheless, their presence in such numbers underscores that, as an older generation of providers retires or otherwise leaves the field, a new generation is entering.

And what a complicated field it is. People affected by the epidemic are often affected by many other challenges, too, such as a life-long struggle with poverty and poor access to health care. HIV service providers and their clients must contend with developments such as compassion fatigue, erosion in community support, the ever-present stigma of HIV/AIDS . . . and, always, the complexities of treatment.

Figure 1: Deaths in Adults and Adolescents With AIDS in the United States

This graph shows the deaths in adults and adolescents with AIDS in the US from 1995 through 2000. D

Source: Centers for Disease Control and Prevention (CDC). HIV/AIDS Surveillance Report. 2001;13(2):30. Table 21.

Entering the field of HIV/AIDS services as a nonclinician and wrapping one’s brain around something as complex as highly active antiretroviral therapy (HAART) is no easy task—but it is an essential one. Nonclinician HIV/AIDS service providers are often pivotal in helping patients prepare for the rigors of HIV/AIDS treatment. They play equally important roles in helping their organizations build services that are culturally competent and reflective of the needs and challenges faced by people living with HIV/AIDS (PLWHA). They can do neither of those things effectively without at least a basic understanding of HAART. This issue of HRSA CAREAction is written to help them acquire that knowledge.

Having HAART

Introduced in 1995, HAART “had an immediate and dramatic impact on the prognosis for HIV infection—[it was] one of the most impressive changes in any disease since the introduction of penicillin in the 1940s.”1 After the introduction of HAART, AIDS-related deaths plummeted from 50,876 in 1995 to 18,028 in 1998 (Figure 1). They have since stabilized.2 The projected life expectancy of patients on antiretroviral therapy is 24.4 years, compared with 12.4 years for patients not receiving antiretroviral therapy.3

HAART, to put it simply, is the use of a combination of different antiretroviral drugs. HAART is often referred to as “combination therapy” and, more colloquially, as a “drug cocktail.” Typically, a HAART regimen has three different drugs, but it can have more. At least two of the drugs in a HAART regimen must come from different drug classes—an important point because each class of drug attacks HIV in a different way.

Currently, more than 20 approved antiretroviral drugs from four different drug classes are available:

  1. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
  2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  3. Protease inhibitors (PIs)
  4. Fusion inhibitors.

See the table at the end of this article for information on specific drugs.

HAART works because it suppresses HIV replication and, thus, reduces the amount of HIV circulating in the body (viral load). The reduction in viral load allows the body’s immune function to improve, which can be measured by the CD4+ T-cell count. (For the definition of this and other technical terms, see "Some Terms You'll Need To Know".) Figure 2 illustrates how the different classes of antiretroviral drugs work at each step of HIV replication.

For the nonclinician seeking to acquire an understanding of the challenges of HAART—or help a client deal with them—the three most important facts to understand are as follows:

  1. HAART is not a one-pill, one-time treatment, but a life-long commitment.
  2. HAART can be laden with side effects.
  3. HAART has strict and unforgiving adherence requirements.

All the HAART-related difficulties with which patients struggle descend from these three facts. If the first were not so—if HAART were a one-time treatment— facts two and three would not matter so much. However, because HAART is an ongoing, never-ending proposition, they matter a lot.

Some Terms You’ll Need to Know

Adherence: Continuous maintenance of a drug regimen; the difficult work of not missing doses for as long as the patient is on the treatment—which, for people living with HIV/AIDS (PLWHA), is for life.

Antiretroviral: An agent that suppresses the activity or replication of retroviruses, such as HIV. Antiretroviral drugs interfere with various stages of the virus’s life cycle.

Asymptomatic: Living with a disease but having no symptoms.

CD4+ count (also called T-cell count): The number of T cells in a small amount of blood; CD4+ cell count is used to measure the strength of a PLWHA’s immune system. When a patient’s T-cell count is less than 200 per mm3, he or she is said to have AIDS. CD4+ cell count in persons not infected with HIV usually ranges from 600 to 1,200 cells per mm3.

CD4+ T cells (also called T cells and T lymphocytes): A type of white blood cell that plays a vital role in the body’s immune response. HIV enters and infects CD4+ cells, disabling them and turning them into “virus factories.”

Co-formulation: Combining more than one medication into a single pill to reduce pill burden and thereby make adherence easier.

Drug resistance: Changes in a virus or bacteria that make treatment ineffective.

Genotypic testing: A type of testing that identifies mutations associated with drug resistance.

HAART (highly active antiretroviral therapy): A combination of at least three drugs from more than one class of antiretroviral agents.

Phenotypic testing: A type of testing that measures the sensitivity of HIV to a specific drug; it reveals how much of a given drug is needed to suppress HIV replication.

Seroconversion: The point at which a person develops HIV antibodies.

Sero-discordant: A couple in which one person is HIV positive and the other is not. Treatment experienced: People who have been treated for HIV.

Treatment naïve: People who have never received a particular treatment. When the term is used in regard to HIV/AIDS it is almost always referring to HAART.

Undetectable viral load: When the viral concentration in the bloodstream is too low for current technologies to detect.

Viral load: The amount of virus in a small sample of a patient’s blood. It is a marker used to determine both when a PLWHA should begin HAART and how well he or she is responding to a HAART regimen. Ideally, viral load should be undetectable during antiretroviral therapy, meaning that the drugs are suppressing HIV replication to extremely low levels.

Viral replication: The process of a virus making copies of itself.

Viral suppression: Reducing the amount of virus in the blood by interfering with viral replication. Viral suppression is the goal of HAART.

Side effects from treatment can be mild, moderate, or severe. They can be occasional, frequent, or constant. In short, they vary according to innumerable factors. But almost universally, side effects can make people not want to take their medicine. For people on HAART, not taking one’s medicine can cause trouble to develop at lightning speed.

The unhappy reality is that patients on HAART have to be much better at adhering to their treatment regimens than do most patients undergoing treatment for other diseases. Just 50 percent of people living with chronic diseases, including asthma, diabetes, and hypertension, take their medications as prescribed more than 80 percent of the time.4 That is not nearly good enough for people on HAART. Results of a study among primarily antiretroviral-experienced patients (i.e., people who had previously been on the kinds of medicines included in HAART) showed that a greater than 95 percent adherence rate was necessary for 78 percent of patients to achieve an undetectable viral load.5

Figure 2. How HAART drugs work

This illustration shows how HAART drugs work.D

Illustration of (1) the virus entering the cell, (2) conversion of viral RNA to DNA using the reverse transcriptase enzyme, (3) incorporation of the viral genome into the DNA of the host cell, (4) viral proteins cleaved by protease for assembly of new viral particles, and (5) new virus particles budding from the surface of the host cell. It also shows the steps in the viral life cycle that are interrupted by (A) fusion inhibitors (B) reverse transcriptase inhibitors and (C) protease inhibitors. Source: National Institutes of Health. Available at Accessed September 20, 2006.

So why is adherence so important? Because HIV replicates rapidly—at rates as high as 10 billion copies per day. With replication rates like that, viral mutations (inexact copies) develop quickly. Some viral mutations confer resistance to a single drug. Others show resistance to an entire class of drugs.

Fortunately, meeting HAART’s adherence demands has become easier during the past 10 years. One reason is that improvements in the drugs have reduced the side effects and long-term problems associated with taking the medications, making them much easier to take on schedule. The importance of this development has been trumped, however, by that of another: the dramatic decline in the number of pills that patients on HAART must take in a single day.

When HAART was introduced, daily pill burdens were measured in the dozens for some patients. In addition to the number of pills, there was the matter of dosing requirements: when to take the pills and with what foods. Some pills were taken twice a day, others as many as six times daily. Some medications were to be taken with food, others to be taken hours before eating and still others made patients nauseous and never want to eat again. In those first years, being on HAART could seem like a fulltime job.

Today, a person on HAART may take as little as one pill per day since the Food and Drug Administration recently approved Atripla, the first once-daily combination of three drugs (Sustiva, Emtriva, and Viread) in a single tablet. Pill burden is also being reduced through an approach called pharmacokinetic “boosting.” The essence of this strategy is to increase the concentration of a drug in the bloodstream and to increase the length of time that the drug stays there. This strategy is implemented by using one drug to increase the concentration of another or lengthening the time the drug stays in the bloodstream by slowing down metabolism.

In addition to reducing side effects and lowering the pill burden, other improvements in the administration of HAART have occurred. Viral load testing determines how active the virus is in the patient’s body and, thus, helps clinicians assess the need for treatment and whether treatment is working. More recently introduced is genotypic and phenotypic resistance testing, which identifies the classes or types of drugs to which a person’s virus has developed resistance and helps clinicians identify the best regimens for their patients. Moreover, new agents that are active against drug-resistant virus have become available, and several promising new drugs from established and new drug classes are in the development pipeline. Advances like these make HAART a much more effective treatment than it was 10 years ago.

In April 1998, the U.S. Department of Health and Human Services and the Centers for Disease Control and Prevention (CDC) issued the first comprehensive, evidence-based HIV treatment guidelines. The guidelines address a variety of issues, including the following:

Treatment guidelines have been updated regularly over the past decade, and guidelines for treating subpopulations such as children and women also have been developed. Several other tools and publications are available for helping patients, clinicians, and nonclinicians understand and administer HAART. See "HIV Treatment Resources" for information on obtaining treatment guidelines and other resources.

HAART All the Time?

The 1998 HIV treatment guidelines suggested an aggressive, “hit early, and hit hard” strategy, which was based on the theory that it was possible to eradicate HIV with HAART (i.e., to “cure” someone of HIV infection). It was soon discovered, however, that complete eradication of HIV is not possible with current therapies, even though some people may have no detectable virus in their bloodstream.

After HAART was widely introduced, reports quickly emerged of side effects. HAART-specific side effects include noticeable changes in body shape, increased diabetes rates, increased cholesterol, and bloating. Other side effects, such as chronic nausea, diarrhea, and peripheral neuropathy (pain, numbness, and tingling in the feet and fingers) are effects of HIV that were compounded by HAART. The side effects negatively affected quality of life and made challenging adherence requirements even more difficult.

Patients beginning treatment with CD4+ counts of less than 200 have poorer survival. Thus, “hit early, hit hard” was modified to the guidelines in place today: It is recommended that HAART be initiated in people whose CD4+ cell counts have fallen to between 201 and 350 per mm3.

Resistance Testing: Genotype and Phenotype

A HAART regimen becomes less effective at suppressing viral replication as mutant strains of HIV develop. Poor adherence to the regimen is a primary cause of viral mutations—but it is not the only cause. Mutant strains of the virus can be transmitted from one person to another. They also can develop over time, even before a person begins antiretroviral therapy, or emerge during treatment as a result of interactions between drugs or problems with the body’s ability to absorb the drugs.

As mutations develop and drug resistance sets in, changing HAART regimens becomes necessary. But the strategy of changing regimens can be implemented only a limited number of times, because the number of viable regimens is finite. Additionally, once resistance develops, drug regimens become much more complicated. There is no “one pill once a day” regimen for highly resistant virus.

Viral mutations are public enemy number one for people on HAART, and they are occurring with increasing frequency. Single-drug and multidrug resistance has been detected in both newly infected and newly diagnosed, treatment-naïve PLWHA. In a 2002 report, Little and colleagues noted a rising incidence of antiretroviral drug resistance among 377 HIV-positive people, all of whom had never been on HAART.6 Over a 5-year period, resistance to a single drug class increased from 3.4 percent to 12.4 percent, and resistance to several drugs increased from 1.1 percent to 6.2 percent. Other studies have reported resistance rates ranging from 8.3 percent to 16.3 percent of untreated, newly infected, or newly diagnosed PLWHA in the United States.7,8

The surge in treatment-resistant virus has made resistance testing a crucial clinical tool for optimizing anti-HIV therapy. Resistance testing results can be combined with patient preference and treatment history, clinician experience, and expert consultation to inform treatment decisions, particularly for treatment-experienced patients.

Complicated Matters

The significant side effects and toxicities referred to above do more than negatively affect adherence. The list of potential long-term complications related to HAART is long and includes cardiovascular disease, renal disease, insulin resistance or diabetes, loss of bone density, and abnormal elevations in lipid (fat) levels (hyperlipidemia).

Lipodystrophy is one of the most talked about side effects of HAART in part because it is the most visible. Lipodystrophy (abnormal fat deposits that change body shape) is disfiguring; the “fat accumulation” type of lipodystrophy often appears as a hump on the upper back or a large potbelly, whereas the “fat loss” type of lipodystrophy—called lipoatrophy—results in hollowed cheeks and a generally gaunt face. These side effects are a significant concern for PLWHA and for the team of care providers working to support them. People who develop these complications often feel that their appearance reveals their HIV status, robbing them of the choice to disclose their status on their own terms. In this sense, they not only lose control of their own bodies but lose control over their identity and privacy.

In addition to their physical manifestations, lipodystrophy and lipoatrophy are sometimes accompanied by abnormally elevated triglycerides (fatty acids), cholesterol, and glucose (blood sugar). Lipodystrophy and lipoatrophy have been reported in people who have used PIs, NNRTIs, and NRTIs as well as in untreated PLWHA. Although a specific cause has yet to be identified, several additional factors have been linked, including genetics, longer duration of antiretroviral therapy, low CD4+ cell count at HIV treatment initiation, older age at treatment initiation, and HIV disease itself.

Strategies for addressing lipodystrophy or lipoatrophy include lifestyle changes, pharmacological interventions, and switching antiretroviral agents. For example, abnormally elevated lipid levels can be managed by changes in diet, increased exercise, and smoking cessation. If those measures are not effective, lipid-lowering agents can be prescribed or treatment regimens can be changed.

Clinicians are still learning about the side effects of HAART and the effects of living with HIV/AIDS as a chronic disease. We do not know the long-term effects of HAART, nor do we know all the interactions between antiretroviral agents and other medications prescribed to address ailments associated with aging. Thus, HIV/AIDS treatment remains a dynamic field, and everyone on the care team—nonclinicians included—has a role to play in ensuring that PLWHA reap the benefits of lessons learned.

HAART: Getting Ready

The answer to the question “when to begin HAART” has changed over the years—and will likely continue to change as treatments for HIV improve. Many things have not changed, of course, and among them is the difficult decision for PLWHA of when to begin HAART.

That HAART can be an unforgiving taskmaster is no secret to PLWHA considering treatment. Its side effects and adherence demands make many people think twice about starting a treatment they will have to continue far into the future. Moreover, many treatment-naïve patients have watched HIV-positive friends and peers wrestle with tough questions that go beyond side effects and adherence: Who’s going to pay for the drugs? Will it keep my other medications from working? How am I going to hide the pills from my mom and the other people who I don’t want to know I’m positive? Add issues like those to the tough circumstances in which many PLWHA live, and it becomes clear why patients may say, “I just can’t do it.”

“We rarely have to discourage people who we believe cannot adhere from entering treatment,” says Laura Cheever, M.D., chief medical officer in the Health Resources and Services Administration (HRSA) HIV/AIDS Bureau. “But we spend an incredible amount of time getting people to a place that they can adhere—and to a place where they believe that they can adhere.”

Cheever is known to many in the CARE Act community as deputy associate administrator in HRSA’s HIV/AIDS Bureau. But she is also an active clinician who serves patients with a history of injection drug use in John Hopkins’ Moore Clinic.

“When T-cell counts in my patients begin to fall toward the levels at which they need to begin HAART,” Cheever explains, “we have a very open and honest discussion about their fears of HAART. The relationships that our patients and team members have established provide the framework for that discussion.”

Preparing patients for treatment is one of the most important services that organizations provide. The nurturing, confidence-giving relationships that develop outside of the doctor-patient interaction are a critical factor in making HAART viable for many patients. But the question of treatment readiness is not merely about patients and their relationship with caregivers; it also involves making sure the caregivers are prepared to help patients become ready. To that end, any serious strategy for preparing patients for treatment should include a team approach.

Addressing HIV/AIDS has never been a one-man or one-woman enterprise, and today, as much as at any time during the pandemic, the care and treatment of PLWHA require the collaboration of professionals from a variety of disciplines along with peers, social workers, and case managers. Without the broad knowledge base that only a team approach can provide, the impoverished, disenfranchised, multiply diagnosed people who are today’s face of AIDS will neither have access to nor be able to reap the full benefits of life-saving HIV medication and treatment.

In many HIV/AIDS service settings, it is social workers, peers, and case managers who spend the most time with PLWHA. People in those roles have long been in pursuit of greater cultural competency and a better understanding of patients’ challenges. In today’s environment, this pursuit must include a quest for an understanding of HAART and its barriers and ramifications. Through providing services to and coming to understand the needs of their clients, HIV/AIDS service providers develop deep, nurturing relationships with their patients. Cheever explains, “These relationships become a source of self-confidence and determination for the patient, and they can help a person whose first response to HAART is to say ‘I can’t’ rethink the issue and say, ‘Well, maybe I can.’”

What's in the Pipeline?

The antiretroviral pipeline is robust, and several drugs from new and established classes of antiretroviral agents are currently in development. Drugs from established classes may offer new therapeutic options for people who have become resistant to existing treatments. New drug classes include

  • entry inhibitors (i.e., those that hinder HIV’s entry into CD4+ cells),
  • integrase inhibitors (i.e., those that obstruct HIV’s integration into cellular DNA), and
  • maturation inhibitors (i.e., those that interfere with the final stages of HIV’s reproduction and movement from cell to cell).

If new agents prove safe and effective, and if side effects and toxicities are minimal and therefore make adherence easier, the HIV treatment model may shift back toward earlier initiation of therapy.


Antiretroviral Drugs: Dosing and Side Effects

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Class-specific adverse events: Lactic acidosis (an abnormal build up of lactic acid in the bloodstream) with hepatic steatosis (fat in the liver) is a rare but potentially life-threatening toxicity associated with use of NRTIs.
Agent (Generic/Brand/
Abbreviation), Approval Date, and Manufacturer
Dosing/Food Restrictions/ Pill Burden Agent-Specific Adverse Events*
December 17, 1998
Once or twice daily, with or without food

Total: 2 pills/day
Hypersensitivity reaction, which can be fatal. Symptoms may include fever; rash; nausea; vomiting; malaise or fatigue; loss of appetite; and respiratory symptoms, such as sore throat, cough, and shortness of breath. (Increased risk of hypersensitivity reaction has been reported with once-daily dosing.)
Didanosine/Videx®/Videx EC®/ddI/ Generic didanosine, enteric coated
Videx®: October 9, 1991
Videx EC®: October 31, 2000
Bristol-Myers Squibb

Generic didanosine:
   December 3, 2004
Barr Laboratories
By weight; once or twice daily, depending on formulation; take Videx EC 1 or 2 hours after a meal; take tablets ½ hour before or 2 hours after a meal

Total: ranges from 2 to 4 pills, or 1 capsule per day, depending on formulation (unless weight is under 133 lbs)
Pancreatitis; peripheral neuropathy (pain, numbness, and tingling in the hands or feet); nausea; diarrhea; vomiting; headache; rash
July 2, 2003
Gilead Sciences
Once daily, with or without food Total: 1 capsule/day Minimal toxicity; side effects include headache, diarrhea, nausea, rash.
November 17, 1995
Once or twice daily, with or without food

Total: 1 or 2 tablets/day (150 or 300 mg)
Minimal toxicity; nausea
June 24, 1994
Bristol-Myers Squibb
By weight; twice daily, with or without food

Total: 2 pills/day (unless weight is under 133 lbs)
Peripheral neuropathy; lipodystrophy; neuromuscular weakness (rare); pancreatitis; higher incidence of lactic acidosis with hepatic steatosis than with other NRTIs; hyperlipidemia
Tenofovir disoproxil fumarate/
October 26, 2001
Gilead Sciences
Once daily, with or without food

Total: 1 pill/day
Asthenia (weakness); headache; diarrhea, nausea, vomiting, and flatulence; renal insufficiency; osteopenia (decrease in bone density rare)
Zalcitibine /HIVID®/ddC
June 19, 1992
Hoffman-La Roche
  Rarely prescribed; discontinuance pending due to toxicity and low potency
March 19, 1987
Twice daily, with or without food

Total: 2 pills/day
Nausea, abdominal pain, asthenia, headache, insomnia, bone marrow suppression leading to anemia (low red blood cell count) and neutropenia (low white blood cell count rare); muscle wasting
Atripla™ (FTC/TDF/EFV)
July 12, 2006
Bristol-Myers Squibb Gilead Sciences (Merck & Co. outside of the United States)
Once daily, on an empty stomach, preferably at bedtime

Total: 1 pill/day
See emtricitabine, tenofovir disoproxil fumarate, and efavirenz
Combivir® (3TC/ZDV)
September 27, 1997
Twice daily, with or without food

Total: 2 pills/day
See lamivudine and zidovudine
Epzicom® (ABC/3TC)
August 2, 2004
Once daily, with or without food

Total: 1 pill/day
See abacavir and lamivudine
Trizivir® (ABC/ZDV/3TC)
November 14, 2000
Twice daily, with or without food

Total: 2 pills/day
See abacavir, lamivudine, and zidovudine
Truvada™ (FTC/TDF)
August 2, 2004
Gilead Sciences
Once daily, with or without food

Total: 1 pill/day
See emtricitabine and tenofovir disoproxil


Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Class-specific adverse events (rare; more commonly reported with NVP than other drugs in this class): Stevens-Johnson syndrome, a severe, potentially life-threatening hypersensitivity reaction; rash
Agent (Generic/Brand/
Abbreviation), Approval Date, and Manufacturer
Dosing/Food Restrictions/ Pill Burden Agent-Specific Adverse Events*
April 4, 1997
Three times daily, with or without food

Total: 6 pills/day
Elevated liver enzymes; headache, fatigue, upset stomach. This drug is rarely used.
September 17, 1998
Bristol- Myers Squibb
Once daily, on an empty stomach, at bedtime

Total: 1 pill/day
Drowsiness, insomnia, vivid dreams, confusion, inability to concentrate, amnesia, hallucinations, euphoria, dizziness, nausea, stomach pain, fever, and elevated liver enzymes; associated with birth defects in monkeys; causes false positive drug test result for cannabis
June 21, 1996
Boehringer Igleheim
Once daily for 14 days (200 mg), twice daily thereafter, with or without food

Total: 2 pills/day; 1 pill/day during14-day lead-in
Hepatitis, which can be asymptomatic; in rare cases, fatal liver damage; headache; upset stomach


Protease Inhibitors (PIs)
Class-specific adverse events: Abnormal distribution of body fat, hyperglycemia (abnormally high blood sugar levels), and possibility of increased bleeding among people with hemophilia are associated with PIs.
Agent (Generic/Brand/
Abbreviation), Approval Date, and Manufacturer
Dosing/Food Restrictions/ Pill Burden Agent-Specific Adverse Events*
April 15, 1999
GlaxoSmithKline/Vertex Pharmaceuticals
Twice daily; avoid taking with high fat meal

Total: oral solution, twice daily
Gastrointestinal intolerance (nausea, vomiting, stomach pain), rash, hyperlipidemia (lipid elevations), elevated liver enzymes, oral tingling or discomfort
June 20, 2003
Bristol-Myers Squibb
Once daily; take with food If treatment-experienced, or if using with TDF or EFV, boost with 100 mg RTV

Total: 2 pills/day if unboosted; otherwise, 3 pills/day (including ritonavir)
Increased bilirubin levels, headache, pain, tingling in arms and legs, nausea, diarrhea, rash, abnormal heartbeat (rare)
June 23, 2006
Tibotec Incorporated
Twice daily, in combination with 100 mg ritonavir; take with food

Total: 6 pills/day (including ritonavir)
Diarrhea, nausea, headache, cold symptoms, mild-to-moderate skin rash
October 20, 2003
GlaxoSmithKline/Vertex Pharmaceuticals
If treatment naïve, twice daily, or can be taken once or twice daily with ritonavir boosting; if treatment-experienced, twice daily with ritonavir boosting, with or without food

Total: 4 pills/day, (with or without ritonavir)
Rash, gastrointestinal intolerance, headache, hyperlipidemia, elevated liver enzymes
March 13, 1996
Merck & Co
Three times/day, or twice daily with ritonavir boosting; if unboosted, take on empty stomach or with light, low-fat snack; if boosted, with or without food

Total: 6 to 8 pills/day, depending on dosing scheme (includes ritonavir)
Kidney stones, gastrointestinal intolerance, elevated bilirubin level, headache, insomnia, rash, back pain, weakness, dizziness, blurred vision, metallic taste, hair loss, low platelets, anemia
Lopinavir ritonavir/
September 15, 2000
Abbott Laboratories
Once daily if treatment naïve; twice daily if treatment experienced, with or without food

Total: 4 pills/day (tablets) 6 pills/day (capsules)
Gastrointestinal intolerance, weakness, headache, elevated liver enzymes, lipid elevations, and pancreatitis (rare)
March 14, 1997
Agouron Pharmaceuticals
Two or three times daily, with snack or meal

Total: ranges from 4 to 10 pills/day, depending on dosing scheme
Diarrhea, gas, rash, hyperlipidemia, elevated liver enzymes
March 1, 1996
Abbott Laboratories
Rarely used as single agent; dosing is three times/day. As a booster, dosing ranges from 100 to 400 mg/day, once or twice daily. If using as single agent, take with full meal.

Total: 12 pills/day
At full dose: gastrointestinal intolerance, numbness and tingling, weakness, hyperlipidemia, liver enzyme elevations, taste perversion
November 7, 1997
December 6, 1995
Hoffman-La Roche
Twice daily; must be ritonavir boosted; take with a full meal

Total: 6 pills/day for invirase, (includes ritonavir)
Gastrointestinal intolerance, insomnia, headache, elevated liver enzymes, hyperlipidemia
Tipranavir/Aptivus®/TPV Boehringer Ingleheim
June 22, 2005
Twice daily, must be ritonavir boosted take with a full meal

Total: 8 pills/day (includes ritonavir)
Rash, gastrointestinal intolerance, fatigue, lipid elevations, hyperglycemia (rare: symptomatic hepatitis, liver failure) (possible: increased risk of intercranial hemorrhage)


Fusion Inhibitors
Agent (Generic/Brand/ Abbreviation), Approval Date, and Manufacturer Dosing/Food Restrictions/ Pill Burden Agent-Specific Adverse Events*
March 13, 2003
Hoffman-La Roche/Trimeris
Two injections/day; must be mixed in advance Injection site reaction: pain, swelling, lumps, hardened skin, bacterial pneumonia, and hypersensitivity reaction (rare; occurs in <1%)

Note: No drugs in this table should be used as monotherapy (this is true for both treatment-naïve and treatment-experienced patients). Darunavir, tipranavir, and enfuvirtide are approved only for use in treatment-experienced people.


HIV Treatment Resources

HIV/AIDS Treatment

Advances in HIV care and treatment are highlighted in “HAART at 10,” a special issue of Research Initiative/Treatment Action! published by the Center for AIDS Information & Advocacy. Available at

Treatment Guidelines

Drug Development

Information on HIV drugs in development is available at

Resistance Testing

Information on resistance testing is available at

HIV Therapy and Management

Other resources include

Additional general information is available at

Information on lipodystrophy and lipoatrophy is available at

Other valuable sites are



  1. Bartlett JG. Antiretroviral therapy. In JG Bartlett, LW Cheever, MP Johnson, DS Paauw, Eds., A guide to primary care of people with HIV/AIDS. Rockville, MD: U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau; 2004: 29- 38. Available at: Accessed September 2006.
  2. Centers for Disease Control and Prevention (CDC). HIV/AIDS Surveillance Report. 2001;13(2):30. Table 21. Available at: Accessed September 20, 2006.
  3. Hutchinson AB, Farnham PG, Dean HD, et al. The economic burden of HIV in the United States in the era of highly active antiretroviral therapy: evidence of continuing racial and ethnic differences. JAIDS [online]. September 14, 2006. Available at:
  4. Cheever LW. Adherence to HIV therapies. In JG Bartlett, LW Cheever, MP Johnson, DS Paauw, Eds., A guide to primary care of people with HIV/AIDS. Rockville, MD: U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau; 2004: 49-54. Available at: Accessed September 2006.
  5. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133:21-30.
  6. Little SJ, Holte S, Routy JP, et al. Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med. 2002;347(6):385-94.
  7. Boden D, Hurley A, Zhang L, et al. HIV-1 drug resistance in newly infected individuals. JAMA. 1999;282(12):1135-41.
  8. Weinstock HS, Zaidi I, Heneine W, et al. The epidemiology of antiretroviral drug resistance among drug- naïve HIV-1 infected persons in 10 US cities. J Infect Dis. 2004;189(12):21 74-80.


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