Antiretroviral drug
Encyclopedia
Antiretroviral drugs are medications for the treatment of infection by retrovirus
es, primarily HIV
. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART. The American National Institutes of Health
and other organizations recommend offering antiretroviral treatment to all patients with AIDS
. Because of the complexity of selecting and following a regimen, the severity of the side-effects and the importance of compliance to prevent viral resistance, such organizations emphasize the importance of involving patients in therapy choices, and recommend analyzing the risks and the potential benefits to patients with low viral loads.
There are different classes of antiretroviral drugs that act on different stages of the HIV life-cycle.
s (AntiViral HyperActivation Limiting Therapeutics or 'virostatics') combine immunomodulating and antiviral properties to inhibit a specific antiviral target while also limiting the hyper-elevated state of immune system activation driving disease progression.
into DNA
via reverse transcription. Its short life-cycle and high error rate cause the virus to mutate very rapidly, resulting in a high genetic variability of HIV. Most of the mutations either are inferior to the parent virus
(often lacking the ability to reproduce at all) or convey no advantage, but some of them have a natural selection
superiority to their parent and can enable them to slip past defenses such as the human immune system and antiretroviral drugs. The more active copies of the virus the greater the possibility that one resistant to antiretroviral drugs will be made.
When antiretroviral drugs are used improperly, these multi-drug resistant strains can become the dominant genotypes very rapidly. Improper serial use of the reverse transcriptase inhibitor
s zidovudine
, didanosine
, zalcitabine, stavudine
, and lamivudine
can lead to the development of multi-drug resistant mutations. The mutations can include the V75I, F77L, K103N, F116Y, Q151M, and the M184V mutation. These mutations were observed before protease inhibitor
s had come into widespread use. The mutants retained sensitivity to the early protease inhibitor saquinavir
. These mutants were also sensitive to the rarely used reverse transcriptase inhibitor foscarnet
.
Antiretroviral combination therapy defends against resistance by suppressing HIV replication as much as possible.
Combinations of antiretrovirals create multiple obstacles to HIV replication to keep the number of offspring low and reduce the possibility of a superior mutation. If a mutation that conveys resistance to one of the drugs being taken arises, the other drugs continue to suppress reproduction of that mutation. With rare exceptions, no individual antiretroviral drug has been demonstrated to suppress an HIV infection for long; these agents must be taken in combinations in order to have a lasting effect. As a result, the standard of care is to use combinations of antiretroviral drugs. Combinations usually comprise two nucleoside-analogue RTIs and one non-nucleoside-analogue RTI or protease inhibitor. This three drug combination is commonly known as a triple cocktail.
Combinations of antiretrovirals are subject to positive and negative synergies
, which limits the number of useful combinations.
In recent years, drug companies have worked together to combine these complex regimens into simpler formulas, termed fixed-dose combinations
. For instance, two pills containing two or three medications each can be taken twice daily. This greatly increases the ease with which they can be taken, which in turn increases adherence, and thus their effectiveness over the long-term. Lack of adherence is a cause of resistance development in medication-experienced patients. Patients who maintain proper therapy can stay on one regimen without developing resistance . This greatly increases life expectancy and leaves more drugs available to the individual should the need arise.
are multiple antiretroviral drugs combined into a single pill.
The preferred initial regimens in the United States, as of June 2011, are:
In 1995, David Ho promoted a "hit hard, hit early" approach with aggressive treatment with multiple antiretrovirals early in the course of the infection. Later reviews noted that this approach of "hit hard, hit early" ran significant risks of increasing side effects and development of multidrug resistance, and this approach was largely abandoned.
The timing of when to initiate therapy has continued to be a core controversy within the medical community. The development of a stable consensus is hampered by the lack of randomized controlled studies with many guidelines and consensus statements basing their recommendations on observational studies. More recently, the trend has been in favor of earlier treatment of asymptomatic HIV patients, with more studies analyzing various treatment regimens in progress.
There is a consensus among experts that, once initiated, antiretroviral therapy should never be stopped. This is because the selection pressure of incomplete suppression of viral replication in the presence of drug therapy causes the more drug sensitive strains to be selectively inhibited. This allows the drug resistant strains to become dominant. This in turn makes it harder to treat the infected individual as well as anyone else they infect.
The current guidelines for antiretroviral therapy (ART) from the World Health Organization
reflect the 2003 changes to the guidelines and recommend that in resource-limited settings (that is, developing nations), HIV-infected adults and adolescents should start ART when HIV infection has been confirmed and one of the following conditions is present :
The treatment guidelines specifically for the USA are set by the United States Department of Health and Human Services (DHHS). The current guidelines for adults and adolescents were stated on December 1, 2009.
• Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with a CD4 count <350 cells/mm3 (AI).
• Antiretroviral therapy should also be initiated, regardless of CD4 count, in patients with the following conditions: pregnancy (AI), HIV- associated nephropathy (AII), and hepatitis B virus (HBV) coinfection when treatment of HBV is indicated (AIII).
• Antiretroviral therapy is recommended for patients with CD4 counts between 350 and 500 cells/mm3. The Panel was divided on the strength of this recommendation: 55% voted for strong recommendation (A) and 45% voted for moderate recommendation (B) (A/B-II).
• For patients with CD4 counts >500 cells/mm3, the Panel was evenly divided: 50% favor starting antiretroviral therapy at this stage of HIV disease (B); 50% view initiating therapy at this stage as optional (C) (B/C-III).
• Patients initiating antiretroviral therapy should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy based on clinical and/or psychosocial factors.
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = expert opinion
+ lamivudine + nevirapine.
. Initial regimens use "first-line" drugs with a high efficacy and low side-effect profile.
Treatment guidelines for HIV-1 infected adults in the developed world (that is, those countries with access to all or most therapies and laboratory tests) have been provided by the International AIDS Society-USA(IAS-USA) since 1996. The IAS-USA is a 501(c)(3) not-for-profit organization in the USA (and is not related to the worldwide International AIDS Society or IAS). The IAS-USA guidelines for antiretroviral therapy are developed by a volunteer panel of experts. Its last update was published in August 2008 in the Journal of the American Medical Association. In the 2008 update, the panel recommended that therapy be initiated before the CD4+ cell count declines to below 350/uL and be individualized for the particular patient's situation and comorbidities. For initial therapy, it recommends 2 NRTIs with either an NNRTI, a ritonavir-boosted PI or an integrase inhibitor. In antiretroviral therapy failure, the goal of subsequent treatment is suppression of HIV-1 RNA to below detection; the treatment should ideally have 3 new drugs to which the patient's virus is susceptible. Therapy in selected clinical situations is also described. The IAS-USA also sponsors the development of guidelines for the use of drug resistance testing in patients with HIV-1 infection
Another set of guidelines (distinct from those of the IAS-USA) are provided by an expert panel convened by the U.S. Department of Health and Human Services
. The preferred initial regimens in the United States, as of June 2011, are:
(AZT) from 28 weeks or as soon as possible thereafter, be provided with single-dose Nevirapine (NVP) when entering labour, and be given AZT+3TC for one week following delivery. Meanwhile, whether the mother was on the above or standard ART, the child should be given single dose Nevirapine immediately after delivery and daily Zidovudine until one week old. Complementary measures that may also be used include caesarean section
and formula feeding; in some settings, the combination of providing all these measures has succeeded in reducing the risk of infection from 25% to about 1%.
that attack and destroy the body's defenses can exacerbate this slowing and increase the risk of developing additional medical problems like diabetes and high blood pressure
, and more physical limitations than younger adults with HIV. In the early years of the HIV epidemic (before HAART), older adults' health deteriorated more rapidly than that of younger individuals - regardless of CD4
count. Several studies found that older adults had lower CD4 counts at diagnosis, faster progression to an AIDS
diagnosis, more opportunistic infections, and a shorter survival rate than younger adults, regardless of when they were first diagnosed with HIV.
Recent studies have found that a person's age does not interfere with the ability of HAART to reduce viral load
, but there may be differences between younger and older people in how well the immune system responds to treatment. A study published in AIDS (2000) by Roberto Manfredi and Francesco Chiodo examined the effect of HAART on older people (defined as 55 or older) compared to younger people (35 or younger). The study included 21 older people (8 women, 13 men) and 84 younger people (29 women, 55 men). The researchers found that both groups responded to HAART, especially in reducing viral load. However, CD4 counts did not increase as much in the older people relative to the younger ones. On average, CD4 counts increased from 212 to 289 for older adults after one year of HAART. During the same period, CD4 counts rose from 231 to 345 for younger people.
Some people may have a very low CD4 count even though they have an undetectable viral load. This may be related to decreased activity in the thymus
(the gland where CD4 cells are made). A 2001 study in AIDS conducted by researchers in Los Angeles included 80 HIV-positive veterans (13 were over 55 and 67 were younger). Although both groups of veterans showed dramatic reductions in viral load once they were on treatment, the researchers found significant differences in CD4 levels at 3, 9, 15, and 18 months. After one year on HAART, average CD4 counts increased by 50 for the older men, compared to increases of 100 for the younger ones. This difference was not related to baseline HIV viral load, coinfection with hepatitis C
, or the race/ethnicity of participants. These studies represent an important first step in understanding how their age may affect older adults' response to HIV treatment, but more studies are needed to understand the long-term effects of age on HAART in older adults.
infection becomes resistant to standard HAART, there are limited options. One option is to take larger combinations of antiretroviral drugs, an approach known as mega-HAART or salvage therapy. Salvage therapy often increases the drugs' side-effects .
If an HIV infection becomes sufficiently resistant to antiretroviral-drugs, treatment becomes more complicated and prognosis may deteriorate. Treatment options continue to improve as additional new drugs enter clinical trials. However, the limited distribution of many such drugs denies their benefits to patients, particularly in the developing world.
s (or "structured treatment interruptions"), are intentional discontinuations of antiretroviral drug treatment.
Intermittent therapy was an experimental approach designed to reduce exposure to antiretroviral drugs in an effort to mitigate side-effects. Intermittent therapy differed from treatment interruptions in that it involved using a much shorter cycle of switching on and off the antiviral drugs. Studies of such approaches include schedules of week-on, week-off (also known as "wowo") and five-days-on, two-days-off (also known as "foto"), which skipped treatment on weekends. Intermittent therapy is ineffective and results in drug resistance.
Suppressing HIV is inadequate to restore normal immune function. HIV can damage the ability of the thymus
to produce normally diverse T-cells. Also, rapid suppression of HIV and partial restoration of the immune system sometimes produces a dangerous hypersensitivity reaction, immune reconstitution inflammatory syndrome
. Research continues in these areas.
With the exception of post exposure prophylaxis, current treatment guidelines do not call for the interruption of drug therapy once it has been initiated.
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
es, primarily HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART. The American National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
and other organizations recommend offering antiretroviral treatment to all patients with AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. Because of the complexity of selecting and following a regimen, the severity of the side-effects and the importance of compliance to prevent viral resistance, such organizations emphasize the importance of involving patients in therapy choices, and recommend analyzing the risks and the potential benefits to patients with low viral loads.
There are different classes of antiretroviral drugs that act on different stages of the HIV life-cycle.
Classes of drugs
Antiretroviral (ARV) drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits.- Entry inhibitorsEntry inhibitorsEntry inhibitors, also known as fusion inhibitors, are a class of antiretroviral drugs, used in combination therapy for the treatment of HIV infection. This class of drugs interferes with the binding, fusion and entry of an HIV virion to a human cell...
(or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets. MaravirocMaravirocMaraviroc is an antiretroviral drug in the CCR5 receptor antagonist class used in the treatment of HIV infection. It is also classed as an entry inhibitor.-Mechanism of action:...
and enfuvirtideEnfuvirtideEnfuvirtide is an HIV fusion inhibitor, the first of a novel class of antiretroviral drugs used in combination therapy for the treatment of HIV-1 infection. It is marketed under the trade name Fuzeon ....
are the two currently available agents in this class. - CCR5 receptor antagonistsDiscovery and development of CCR5 receptor antagonistsCCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor CCR5 is involved in the HIV entry process...
are the first antiretroviral drugs which do not target the virus directly. Instead, they bind to the CCR5 receptor on the surface of the T-Cell and block viral attachment to the cell. Most strains of HIV attach to T-Cells using the CCR5 receptor. If HIV cannot attach to the cell, it cannot gain entry to replicate. - Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI)Reverse transcriptase inhibitorReverse-transcriptase inhibitors are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase enzyme that retroviruses need to reproduce.-Mechanism:...
inhibit reverse transcription by being incorporated into the newly synthesized viral DNA strand as a faulty nucleotideNucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
. This causes a chemical reaction resulting in DNA chain termination. - Non-nucleoside reverse transcriptase inhibitors (NNRTI)Reverse transcriptase inhibitorReverse-transcriptase inhibitors are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase enzyme that retroviruses need to reproduce.-Mechanism:...
inhibit reverse transcriptase directly by binding to the enzyme and interfering with its function. - Protease inhibitorsProtease inhibitor (pharmacology)Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...
(PIs) target viral assembly by inhibiting the activity of proteaseProteaseA protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
, an enzyme used by HIV to cleave nascent proteinProteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s for the final assembly of new virions. - Integrase inhibitorIntegrase inhibitorIntegrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus...
s inhibit the enzyme integraseIntegraseRetroviral integrase is an enzyme produced by a retrovirus that enables its genetic material to be integrated into the DNA of the infected cell...
, which is responsible for integration of viral DNA into the DNA of the infected cell. There are several integrase inhibitors currently under clinical trial, and raltegravir became the first to receive FDA approval in October 2007. - Maturation inhibitorMaturation inhibitorThe maturation inhibitors are a class of antiviral drugs for the treatment of infection with HIV. They act by interfering with the maturation of the virus. Specifically, drugs in this class disrupt the final step in the processing of the HIV-1 Gag protein, leading to the formation of...
s inhibit the last step in gag processing in which the viral capsid polyprotein is cleaved, thereby blocking the conversion of the polyprotein into the mature capsid protein (p24). Because these viral particles have a defective core, the virions released consist mainly of non-infectious particles. Alpha interferonInterferonInterferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
is a currently available agent in this class. Two additional inhibitors under investigation are bevirimatBevirimatBevirimat is an anti-HIV drug derived from a betulinic acid-like compound, first isolated from Syzygium claviflorum, a Chinese herb. It is believed to inhibit HIV by a novel mechanism, so-called maturation inhibition. It is not currently U.S. Food and Drug Administration approved, but is...
and ViveconViveconVivecon is an investigational new drug in development for the treatment of HIV infection. It is a maturation inhibitor.-Mechanism of action:Vivecon targets the gag polyprotein precursor, the main structural protein responsible for assembly and budding of virion particles. By binding to the gag...
.
Anti-viral hyperactivation limiting therapeutics
AV-HALTAV-HALT
AntiViral-HyperActivation Limiting Therapeutics are an investigational class of antiretroviral drugs used to treat Human Immunodeficiency Virus infection...
s (AntiViral HyperActivation Limiting Therapeutics or 'virostatics') combine immunomodulating and antiviral properties to inhibit a specific antiviral target while also limiting the hyper-elevated state of immune system activation driving disease progression.
Combination therapy
The life cycle of HIV can be as short as about 1.5 days from viral entry into a cell, through replication, assembly, and release of additional viruses, to infection of other cells. HIV lacks proofreading enzymes to correct errors made when it converts its RNARNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
into DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
via reverse transcription. Its short life-cycle and high error rate cause the virus to mutate very rapidly, resulting in a high genetic variability of HIV. Most of the mutations either are inferior to the parent virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
(often lacking the ability to reproduce at all) or convey no advantage, but some of them have a natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
superiority to their parent and can enable them to slip past defenses such as the human immune system and antiretroviral drugs. The more active copies of the virus the greater the possibility that one resistant to antiretroviral drugs will be made.
When antiretroviral drugs are used improperly, these multi-drug resistant strains can become the dominant genotypes very rapidly. Improper serial use of the reverse transcriptase inhibitor
Reverse transcriptase inhibitor
Reverse-transcriptase inhibitors are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase enzyme that retroviruses need to reproduce.-Mechanism:...
s zidovudine
Zidovudine
Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
, didanosine
Didanosine
Didanosine is sold under the trade names Videx and Videx EC. It is a reverse transcriptase inhibitor, effective against HIV and used in combination with other antiretroviral drug therapy as part of highly active antiretroviral therapy .-History:The related pro-drug of didanosine,...
, zalcitabine, stavudine
Stavudine
Stavudine is a nucleoside analog reverse transcriptase inhibitor active against HIV.-History:...
, and lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
can lead to the development of multi-drug resistant mutations. The mutations can include the V75I, F77L, K103N, F116Y, Q151M, and the M184V mutation. These mutations were observed before protease inhibitor
Protease inhibitor (pharmacology)
Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...
s had come into widespread use. The mutants retained sensitivity to the early protease inhibitor saquinavir
Saquinavir
Saquinavir is an antiretroviral drug used in HIV therapy. It falls in the protease inhibitor class. Two formulations have been marketed:*a hard-gel capsule formulation of the mesylate, with trade name Invirase, which requires combination with ritonavir to increase the saquinavir bioavailability;*a...
. These mutants were also sensitive to the rarely used reverse transcriptase inhibitor foscarnet
Foscarnet
Foscarnet is the conjugate base of the chemical compound with the formula HO2CPO3H2.-Uses:This phosphonic acid derivative is an antiviral medication used to treat herpes viruses, including drug resistant cytomegalovirus and herpes simplex viruses types 1 and 2...
.
Antiretroviral combination therapy defends against resistance by suppressing HIV replication as much as possible.
Combinations of antiretrovirals create multiple obstacles to HIV replication to keep the number of offspring low and reduce the possibility of a superior mutation. If a mutation that conveys resistance to one of the drugs being taken arises, the other drugs continue to suppress reproduction of that mutation. With rare exceptions, no individual antiretroviral drug has been demonstrated to suppress an HIV infection for long; these agents must be taken in combinations in order to have a lasting effect. As a result, the standard of care is to use combinations of antiretroviral drugs. Combinations usually comprise two nucleoside-analogue RTIs and one non-nucleoside-analogue RTI or protease inhibitor. This three drug combination is commonly known as a triple cocktail.
Combinations of antiretrovirals are subject to positive and negative synergies
Synergy
Synergy may be defined as two or more things functioning together to produce a result not independently obtainable.The term synergy comes from the Greek word from , , meaning "working together".-Definitions and usages:...
, which limits the number of useful combinations.
In recent years, drug companies have worked together to combine these complex regimens into simpler formulas, termed fixed-dose combinations
Fixed dose combination (antiretroviral)
Fixed-dose combinations of antiretrovirals are multiple antiretroviral drugs combined into a single pill, which helps reduce pill burden. They may combine different classes of antiretrovirals or contain only a single class. Licensed fixed-dose combinations are shown in the table below....
. For instance, two pills containing two or three medications each can be taken twice daily. This greatly increases the ease with which they can be taken, which in turn increases adherence, and thus their effectiveness over the long-term. Lack of adherence is a cause of resistance development in medication-experienced patients. Patients who maintain proper therapy can stay on one regimen without developing resistance . This greatly increases life expectancy and leaves more drugs available to the individual should the need arise.
Fixed-dose combinations
Fixed dose combinationsFixed dose combination (antiretroviral)
Fixed-dose combinations of antiretrovirals are multiple antiretroviral drugs combined into a single pill, which helps reduce pill burden. They may combine different classes of antiretrovirals or contain only a single class. Licensed fixed-dose combinations are shown in the table below....
are multiple antiretroviral drugs combined into a single pill.
| Brand Name | Drug Names (INN International Nonproprietary Name An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization... ) | Date of FDA Approval | Company |
|---|---|---|---|
| Combivir Combivir Lamivudine/zidovudine is a pharmaceutical treatment for HIV infection. It is a fixed dose combination of two antiretroviral drugs, lamivudine and zidovudine... |
zidovudine Zidovudine Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine.... + lamivudine Lamivudine Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV... |
September 26, 1997 | GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom... |
| Trizivir Trizivir Abacavir/lamivudine/zidovudine is a pharmaceutical treatment for HIV infection. It is a fixed dose combination of three reverse transcriptase inhibitors patented by GlaxoSmithKline and now marketed by its joint venture with Pfizer, ViiV Healthcare:*abacavir *lamivudine *zidovudine It is indicated... |
abacavir Abacavir Abacavir is a nucleoside analog reverse transcriptase inhibitor used to treat HIV and AIDS. It is available under the trade name Ziagen and in the combination formulations Trizivir and Kivexa/Epzicom... + zidovudine Zidovudine Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine.... + lamivudine Lamivudine Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV... |
November 15, 2000 | GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom... |
| Kaletra Lopinavir Lopinavir is an antiretroviral of the protease inhibitor class. It is used as a fixed-dose combination with another protease inhibitor, ritonavir, under the trade names Kaletra and Aluvia .... |
lopinavir Lopinavir Lopinavir is an antiretroviral of the protease inhibitor class. It is used as a fixed-dose combination with another protease inhibitor, ritonavir, under the trade names Kaletra and Aluvia .... + ritonavir Ritonavir Ritonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS.... |
September 15, 2000 | Abbott Laboratories Abbott Laboratories Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr.... |
| Epzicom Epzicom Abacavir/lamivudine is a combination drug for the treatment of HIV infection. It is marketed as Kivexa in most countries except for the United States, where it is branded as Epzicom... (in USA) Kivexa (in Europe) |
abacavir Abacavir Abacavir is a nucleoside analog reverse transcriptase inhibitor used to treat HIV and AIDS. It is available under the trade name Ziagen and in the combination formulations Trizivir and Kivexa/Epzicom... + lamivudine Lamivudine Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV... |
August 2, 2004 | GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom... |
| Truvada Truvada Tenofovir/emtricitabine, trademark Truvada, is a fixed-dose combination of two antiretroviral drugs used for the treatment of HIV. It consists of 300 milligrams of tenofovir and 200 milligrams of emtricitabine. By combining the two agents into one tablet, it reduces the pill burden and increases... |
tenofovir/emtricitabine | August 2, 2004 | Gilead Sciences Gilead Sciences Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two... |
| Atripla Atripla Emtricitabine/tenofovir/efavirenz is a fixed-dose combination drug for the treatment of HIV infection. It combines Gilead Sciences's tenofovir and emtricitabine with Bristol-Myers Squibb's efavirenz into a fixed-dose pill... |
efavirenz Efavirenz Efavirenz is a non-nucleoside reverse transcriptase inhibitor and is used as part of highly active antiretroviral therapy for the treatment of a human immunodeficiency virus type 1.... + tenofovir/emtricitabine |
July 12, 2006 | Gilead Sciences Gilead Sciences Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two... and Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation... |
The preferred initial regimens in the United States, as of June 2011, are:
- Tenofovir/emtricitabine (a combination of two NRTIs) and efavirenzEfavirenzEfavirenz is a non-nucleoside reverse transcriptase inhibitor and is used as part of highly active antiretroviral therapy for the treatment of a human immunodeficiency virus type 1....
(a NNRTI). Efavirenz should not be given to pregnant women. - tenofovir/emtricitabine and raltegravir (an integrase inhibitorIntegrase inhibitorIntegrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus...
) - tenofovir/emtricitabine, ritonavirRitonavirRitonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....
and darunavirDarunavirDarunavir is a drug used to treat HIV infection. It is in the protease inhibitor class. Prezista is an OARAC recommended treatment option for treatment-naïve and treatment-experienced adults and adolescents. Developed by pharmaceutical company Tibotec, darunavir is named after Arun K...
(both latter are protease inhibitorProtease inhibitorProtease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...
s) - tenofovir/emtricitabine, ritonavir and atazanavirAtazanavirAtazanavir, marketed under the trade name Reyataz by Bristol Myers, is an antiretroviral drug of the protease inhibitor class...
(both latter are protease inhibitors)
Initiation of antiretroviral therapy
Antiretroviral drug treatment guidelines have changed over time. Prior to 1987, no antiretroviral drugs were available and treatment consisted of treating complications from the immunodeficiency. After antiretroviral medications were introduced, most clinicians agreed that HIV positive patients with low CD4 counts should be treated, but no consensus formed as to whether to treat patients with high CD4 counts.In 1995, David Ho promoted a "hit hard, hit early" approach with aggressive treatment with multiple antiretrovirals early in the course of the infection. Later reviews noted that this approach of "hit hard, hit early" ran significant risks of increasing side effects and development of multidrug resistance, and this approach was largely abandoned.
The timing of when to initiate therapy has continued to be a core controversy within the medical community. The development of a stable consensus is hampered by the lack of randomized controlled studies with many guidelines and consensus statements basing their recommendations on observational studies. More recently, the trend has been in favor of earlier treatment of asymptomatic HIV patients, with more studies analyzing various treatment regimens in progress.
There is a consensus among experts that, once initiated, antiretroviral therapy should never be stopped. This is because the selection pressure of incomplete suppression of viral replication in the presence of drug therapy causes the more drug sensitive strains to be selectively inhibited. This allows the drug resistant strains to become dominant. This in turn makes it harder to treat the infected individual as well as anyone else they infect.
Current guidelines
The current guidelines use new criteria to consider starting HAART, as described below. However, there remain a range of views on this subject and the decision of whether to commence treatment ultimately rests with the patient and their doctor.The current guidelines for antiretroviral therapy (ART) from the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
reflect the 2003 changes to the guidelines and recommend that in resource-limited settings (that is, developing nations), HIV-infected adults and adolescents should start ART when HIV infection has been confirmed and one of the following conditions is present :
- Clinically advanced HIV disease;
- WHO Stage IV HIV disease, irrespective of the CD4 cell count;
- WHO Stage III disease with consideration of using CD4 cell counts less than 350/µl to assist decision making;
- WHO Stage I or II HIV disease with CD4 cell counts less than 200/µl.
The treatment guidelines specifically for the USA are set by the United States Department of Health and Human Services (DHHS). The current guidelines for adults and adolescents were stated on December 1, 2009.
• Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with a CD4 count <350 cells/mm3 (AI).
• Antiretroviral therapy should also be initiated, regardless of CD4 count, in patients with the following conditions: pregnancy (AI), HIV- associated nephropathy (AII), and hepatitis B virus (HBV) coinfection when treatment of HBV is indicated (AIII).
• Antiretroviral therapy is recommended for patients with CD4 counts between 350 and 500 cells/mm3. The Panel was divided on the strength of this recommendation: 55% voted for strong recommendation (A) and 45% voted for moderate recommendation (B) (A/B-II).
• For patients with CD4 counts >500 cells/mm3, the Panel was evenly divided: 50% favor starting antiretroviral therapy at this stage of HIV disease (B); 50% view initiating therapy at this stage as optional (C) (B/C-III).
• Patients initiating antiretroviral therapy should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy based on clinical and/or psychosocial factors.
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = expert opinion
Baseline resistance
In countries with a high rate of baseline resistance, resistance testing is recommended prior to starting treatment; or, if the initiation of treatment is urgent, then a "best guess" treatment regimen should be started, which is then modified on the basis of resistance testing. In the UK, there is 11.8% medium to high-level resistance at baseline to the combination of efavirenz + zidovudine + lamivudine, and 6.4% medium to high level resistance to stavudineStavudine
Stavudine is a nucleoside analog reverse transcriptase inhibitor active against HIV.-History:...
+ lamivudine + nevirapine.
Regimens
Most current HAART regimens consist of three(3) drugs: 2 NRTIs + a PI/NNRTI/IIIntegrase inhibitor
Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus...
. Initial regimens use "first-line" drugs with a high efficacy and low side-effect profile.
Treatment guidelines for HIV-1 infected adults in the developed world (that is, those countries with access to all or most therapies and laboratory tests) have been provided by the International AIDS Society-USA(IAS-USA) since 1996. The IAS-USA is a 501(c)(3) not-for-profit organization in the USA (and is not related to the worldwide International AIDS Society or IAS). The IAS-USA guidelines for antiretroviral therapy are developed by a volunteer panel of experts. Its last update was published in August 2008 in the Journal of the American Medical Association. In the 2008 update, the panel recommended that therapy be initiated before the CD4+ cell count declines to below 350/uL and be individualized for the particular patient's situation and comorbidities. For initial therapy, it recommends 2 NRTIs with either an NNRTI, a ritonavir-boosted PI or an integrase inhibitor. In antiretroviral therapy failure, the goal of subsequent treatment is suppression of HIV-1 RNA to below detection; the treatment should ideally have 3 new drugs to which the patient's virus is susceptible. Therapy in selected clinical situations is also described. The IAS-USA also sponsors the development of guidelines for the use of drug resistance testing in patients with HIV-1 infection
Another set of guidelines (distinct from those of the IAS-USA) are provided by an expert panel convened by the U.S. Department of Health and Human Services
United States Department of Health and Human Services
The United States Department of Health and Human Services is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. Its motto is "Improving the health, safety, and well-being of America"...
. The preferred initial regimens in the United States, as of June 2011, are:
- tenofovir/emtricitabine (a combination of two NRTIs) and efavirenzEfavirenzEfavirenz is a non-nucleoside reverse transcriptase inhibitor and is used as part of highly active antiretroviral therapy for the treatment of a human immunodeficiency virus type 1....
(a NNRTI). Efavirenz should not be given to pregnant women. - tenofovir/emtricitabine and raltegravir (an integrase inhibitorIntegrase inhibitorIntegrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus...
) - tenofovir/emtricitabine, ritonavirRitonavirRitonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....
and darunavirDarunavirDarunavir is a drug used to treat HIV infection. It is in the protease inhibitor class. Prezista is an OARAC recommended treatment option for treatment-naïve and treatment-experienced adults and adolescents. Developed by pharmaceutical company Tibotec, darunavir is named after Arun K...
(both latter are protease inhibitorProtease inhibitorProtease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...
s) - tenofovir/emtricitabine, ritonavir and atazanavirAtazanavirAtazanavir, marketed under the trade name Reyataz by Bristol Myers, is an antiretroviral drug of the protease inhibitor class...
(both latter are protease inhibitors)
Children
Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, in particular for young infants, treatment recommendations from the DHHS have been more aggressive in children than in adults; the current guidelines were published November 3, 2005.HIV Postexposure Prophylaxis (PEP)
In 2005, the Centers for Disease Control and Prevention in the United States recommended a 28-day HIV drug regimen for those that have been exposed to HIV (HIV Postexposure Prophylaxis [PEP]). The WHO recommendations on treatment are that the minimum that should be used is dual NRTIs for 28 days, with triple therapy (dual NRTIs plus a boosted PI) being offered where there is a risk of resistance. The effectiveness of this intervention has never been precisely ascertained, but postexposure prophylaxis is most effective when administered sooner, though not believed to be effective if given 72 hours after exposure.Prevention of mother-to-child-transmission (PMTCT)
The use of antiretrovirals is also recommended for the prevention of mother-to-child transmission of HIV-1. The current WHO recommended regimen is as follows: where the pregnant woman does not yet need to start ART for therapeutic reasons, she should start ZidovudineZidovudine
Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
(AZT) from 28 weeks or as soon as possible thereafter, be provided with single-dose Nevirapine (NVP) when entering labour, and be given AZT+3TC for one week following delivery. Meanwhile, whether the mother was on the above or standard ART, the child should be given single dose Nevirapine immediately after delivery and daily Zidovudine until one week old. Complementary measures that may also be used include caesarean section
Caesarean section
A Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...
and formula feeding; in some settings, the combination of providing all these measures has succeeded in reducing the risk of infection from 25% to about 1%.
Concerns
There are several concerns about antiretroviral regimens:- intolerance: The drugs can have serious side-effects, particularly in advanced disease.
- resistance: If patients miss doses, drug resistance can develop,
- cost: Providing anti-retroviral treatment is costly and resource-intensive, and the majority of the world's infected individuals cannot access treatment services.
- public health: Individuals who fail to use antiretrovirals properly can develop multi-drug resistant strains which can be passed onto others.
Responses to treatment in older adults
As people age, their bodies are not able to repair and rebuild damaged cells, organs or tissues as rapidly as those of younger people. Diseases like HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
that attack and destroy the body's defenses can exacerbate this slowing and increase the risk of developing additional medical problems like diabetes and high blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, and more physical limitations than younger adults with HIV. In the early years of the HIV epidemic (before HAART), older adults' health deteriorated more rapidly than that of younger individuals - regardless of CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
count. Several studies found that older adults had lower CD4 counts at diagnosis, faster progression to an AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
diagnosis, more opportunistic infections, and a shorter survival rate than younger adults, regardless of when they were first diagnosed with HIV.
Recent studies have found that a person's age does not interfere with the ability of HAART to reduce viral load
Viral load
Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...
, but there may be differences between younger and older people in how well the immune system responds to treatment. A study published in AIDS (2000) by Roberto Manfredi and Francesco Chiodo examined the effect of HAART on older people (defined as 55 or older) compared to younger people (35 or younger). The study included 21 older people (8 women, 13 men) and 84 younger people (29 women, 55 men). The researchers found that both groups responded to HAART, especially in reducing viral load. However, CD4 counts did not increase as much in the older people relative to the younger ones. On average, CD4 counts increased from 212 to 289 for older adults after one year of HAART. During the same period, CD4 counts rose from 231 to 345 for younger people.
Some people may have a very low CD4 count even though they have an undetectable viral load. This may be related to decreased activity in the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
(the gland where CD4 cells are made). A 2001 study in AIDS conducted by researchers in Los Angeles included 80 HIV-positive veterans (13 were over 55 and 67 were younger). Although both groups of veterans showed dramatic reductions in viral load once they were on treatment, the researchers found significant differences in CD4 levels at 3, 9, 15, and 18 months. After one year on HAART, average CD4 counts increased by 50 for the older men, compared to increases of 100 for the younger ones. This difference was not related to baseline HIV viral load, coinfection with hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
, or the race/ethnicity of participants. These studies represent an important first step in understanding how their age may affect older adults' response to HIV treatment, but more studies are needed to understand the long-term effects of age on HAART in older adults.
Mega-HAART
If an HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection becomes resistant to standard HAART, there are limited options. One option is to take larger combinations of antiretroviral drugs, an approach known as mega-HAART or salvage therapy. Salvage therapy often increases the drugs' side-effects .
If an HIV infection becomes sufficiently resistant to antiretroviral-drugs, treatment becomes more complicated and prognosis may deteriorate. Treatment options continue to improve as additional new drugs enter clinical trials. However, the limited distribution of many such drugs denies their benefits to patients, particularly in the developing world.
Structured treatment interruptions
Drug holidayDrug holiday
A drug holiday is when a patient stops taking a medication for a period of time; anywhere from a few days to many months or even years if they feel it is in their best interests.Planned drug holidays are used in numerous fields of...
s (or "structured treatment interruptions"), are intentional discontinuations of antiretroviral drug treatment.
Intermittent therapy was an experimental approach designed to reduce exposure to antiretroviral drugs in an effort to mitigate side-effects. Intermittent therapy differed from treatment interruptions in that it involved using a much shorter cycle of switching on and off the antiviral drugs. Studies of such approaches include schedules of week-on, week-off (also known as "wowo") and five-days-on, two-days-off (also known as "foto"), which skipped treatment on weekends. Intermittent therapy is ineffective and results in drug resistance.
Suppressing HIV is inadequate to restore normal immune function. HIV can damage the ability of the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
to produce normally diverse T-cells. Also, rapid suppression of HIV and partial restoration of the immune system sometimes produces a dangerous hypersensitivity reaction, immune reconstitution inflammatory syndrome
Immune reconstitution inflammatory syndrome
Immune reconstitution inflammatory syndrome is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the...
. Research continues in these areas.
With the exception of post exposure prophylaxis, current treatment guidelines do not call for the interruption of drug therapy once it has been initiated.
Adverse effects
Adverse effects of antiretroviral drugs vary by drug, by ethnicity, by individual, and by interaction with other drugs, including alcohol. Hypersensitivity to some drugs may also occur in some individuals. The following list is not complete, but includes several of the adverse effects experienced by patients taking some antiretroviral drugs:- Abdominal painAbdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
(Ritonavir) - AlopeciaAlopeciaAlopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
(INF-alpha) - AnemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
(AZT) - Asthenia
- DiarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
(Abacavir) - DizzinessDizzinessDizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
(Vertigo) - Fanconi syndromeFanconi syndromeFalconi syndrome is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid...
- FlatulenceFlatulenceFlatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
(Tenofovir ) - GynecomastiaGynecomastiaGynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
- HeadacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
(3TC overdose) - HepatitisHepatitisHepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
- Hyperbilirubinemia
- HypercholesterolemiaHypercholesterolemiaHypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
- HyperpigmentationHyperpigmentationIn dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
(Emtricitabine) - Ingrown nailIngrown nailOnychocryptosis , also known as an ingrown toenail, or unguis incarnatus is a common form of nail disease. It is an often painful condition in which the nail grows so that it cuts into one or both sides of the paronychium or nail bed...
s (IDV) - InsomniaInsomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
(Emtricitabine ) - JaundiceJaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
- LipodystrophyLipodystrophyLipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy is used when describing the loss of fat from one area...
/ HIV-associated lipodystrophyHIV-associated lipodystrophyHIV-associated lipodystrophy is a condition characterized by loss of subcutaneous fat associated with infection with HIV.-Cause:The exact mechanism of HIV-associated lipodystrophy is not fully elucidated... - Liver failureLiver failureAcute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
- MalaiseMalaiseMalaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
- Mental confusionMental confusionConfusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
(EVZ ) - MigraineMigraineMigraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
s - Mitochondrial toxicityMitochondrial toxicityMitochondrial toxicity is a condition in which the mitochondria of a body's cells become damaged or decline significantly in number; it occurs as a side effect of certain antiretroviral drugs used to treat human immunodeficiency virus, or HIV.-Causes:...
(ddI > d4T > AZT) - Mood swingMood swing-Associated disorders:Mood swings are commonly associated with mood disorders including bipolar disorder and depression. In patients with cases of bipolar disorder, the patient experiences serious mood swings that last for days or even weeks...
s - MyalgiaMyalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
(AZT overdose) - MyopathyMyopathyIn medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
(AZT overdose) - NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
(AZT) - NeutropeniaNeutropeniaNeutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
(AZT) - NightmareNightmareA nightmare is an unpleasant dream that can cause a strong negative emotional response from the mind, typically fear or horror, but also despair, anxiety and great sadness. The dream may contain situations of danger, discomfort, psychological or physical terror...
s (EFZ) - Oral ulcers (ddC)
- PancreatitisPancreatitisPancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
(ddI) - ParesthesiaParesthesiaParesthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
(IDV) - Peripheral neuropathyPeripheral neuropathyPeripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
(ddI, ddC, d4T) - RashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
- Renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
or insufficiency (IDV, TDF) - SomnolenceSomnolenceSomnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
(drowsiness) - Stevens–Johnson syndrome
- Change in tasteTasteTaste is one of the traditional five senses. It refers to the ability to detect the flavor of substances such as food, certain minerals, and poisons, etc....
perception - VomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
(AZT) - XerodermaXerodermaXeroderma, literally meaning "dry skin", is a condition involving the integumentary system, which in most cases can safely be treated with emollients and/or moisturizers. Xeroderma occurs most commonly on the scalp, lower legs, arms, the knuckles, the sides of the abdomen and thighs...
(dry skin) - XerostomiaXerostomiaXerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
(dry mouth)
See also
- Antiviral drugAntiviral drugAntiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
- Discovery and Development of HIV Protease InhibitorsDiscovery and development of HIV protease inhibitorsMany major physiological processes depend on regulation of proteolytic enzyme activity and there can be dramatic consequences when equilibrium between an enzyme and its substrates is disturbed. In this prospective, the discovery of small-molecule ligands, like protease inhibitors, that can modulate...
- Discovery and Development of Non-Nucleoside Reverse Transcriptase InhibitorsDiscovery and development of non-nucleoside reverse transcriptase inhibitorsNon-nucleoside reverse-transcriptase inhibitors are antiretroviral drugs used in the treatment of human immunodeficiency virus . NNRTIs inhibit reverse transcriptase , an enzyme that controls the replication of the genetic material of HIV...
- Discovery and development of nucleoside and nucleotide reverse transcriptase inhibitors
Further reading
- Cohen, Mardge H., MD, et al., "Medically Eligible Women Who Do Not Use HAART: The Importance of Abuse, Drug Use, and Race", American Journal of Public Health, Vol 94, No. 7, July 2004, pp. 1147–1151. American Public Health Association
- Cohen, Mardge H., MD, et al., "Impact of Highly Active Antiretroviral Therapy on Anemia and Relationship Between Anemia and Survival in a Large Cohort of HIV-Infected Women: Women's Interagency HIV Study", MedscapeMedscapeMedscape is a web resource for physicians and other health professionals. It features peer-reviewed original medical journal articles, CME , a customized version of the National Library of Medicine's MEDLINE database, daily medical news, major conference coverage, and drug information—including a...
CME, 11/17/2004
External links
- AIDSinfo - Comprehensive resource for HIV/AIDS treatment and clinical trial information from the U. S. Department of Health and Human Services
- Origins of antiretroviral combination therapy
- Viral Load research papers, including effectiveness of HAART on reducing viral load
- Current status of gene therapy strategies to treat HIV/AIDS