However, the study authors caution that their results, which include only 48 weeks of trial data, are still preliminary. Longer follow-up periods will be necessary to ensure the regimen will be safe and effective long-term.

Currently, the standard treatment regimen for HIV includes at least three antiretroviral medications from two different drug classes, usually two nucleoside reverse transcriptase inhibitors (NRTIs), plus either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor (PI).

This combination therapy is generally successful in decreasing HIV replication, increasing healthy CD4 cell counts, and partially restoring the immune system.

However, there have been a number of short- and long-term harmful side effects reported in response to the current combination ART, especially with protease inhibitor-based therapy.

Some of the side effects include hyperlipidemia (elevation of lipids, such as cholesterol, in the blood), insulin resistance, lipodystrophy (abnormal fat redistribution), and an increased risk of heart problems.

As a result, researchers have explored simplified ART maintenance regimens that do not contain protease inhibitors as an alternative long-term drug option.

In this study, participants who had never received antiretroviral therapy were treated first with a standard dual NRTI/PI regimen, consisting of Combivir (zidovudine/lamivudine) plus Kaletra (lopinavir/ritonavir).

After achieving viral suppression (viral load, or amount of HIV virus in the blood, of less than 50 copies/milliliter), participants were randomly assigned to either continue the Combivir/Kaletra regimen, or switch to Trizivir.

Trizivir is a triple-NRTI regimen, and does not contain a protease inhibitor. Previous studies have shown Trizivir is associated with more favorable lipids and fewer drug interactions compared to regimens containing protease inhibitors.

The study showed that Trizivir was as good as Combivir/Kaletra at maintaining viral suppression halfway through the study, at 48 weeks. The trial will continue for an additional 48 weeks.

Additionally, researchers noted that the NRTI-only regimen, Trizivir, decreased participants’ pill burden from six or eight pills per day to two per day, which could improve adherence.

Adherence – taking medications as prescribed – is important to reduce HIV drug resistance and maintain virus suppression.

The researchers did note some limitations to the study, including a small sample size; only about 100 participants were analyzed. This was partly because the researchers were strict about allowing participants to continue, which could bias the study results toward a favorable outcome.

The study was also open-label, which means participants knew which medications they were taking.

Finally, the results only cover a fairly short duration, which means that it may be too early to predict the success of the treatment long-term.

Safety and effectiveness of the drug regimen will be studied after the full 96 weeks of the study are completed, which is expected to give more information on its long-term potential.

For more information, please see the study in AIDS Patient Care And STDs.

Sustiva, which is an antiretroviral drug made by Bristol-Myers Squibb, is approved by the FDA for use in combination with other antiretroviral agents in HIV-positive adults and children older than three years of age.

Sustiva is classified as a Pregnancy Category D drug, indicating there is evidence it can cause birth defects.

The new label has updated information on fetal harm, including neural tube defects (birth defects of the brain and spinal cord), that can occur if Sustiva is taken during the first trimester of pregnancy.

The Antiretroviral Pregnancy Registry, which monitors fetal outcomes of pregnant women exposed to Sustiva, reported birth defects in about three percent of live births involving first-trimester exposure to Sustiva, and in just over 3.5 percent of live births involving second/third-trimester exposure.

Additionally, the revised label warns of potential liver toxicity in people taking Sustiva.

Although most cases of serious liver problems occurred in patients with pre-existing liver dysfunction, a few cases occurred in patients without any pre-existing liver disease.

The liver problems encountered sometimes culminated in transplantation or death.

As a result, the FDA recommends considering liver enzyme monitoring in Sustiva patients, regardless of whether they have pre-existing liver dysfunction or not.

The label also cautions that Noxafil (posaconazole), which is used to treat Candida and other yeast infections, only be taken in combination with Sustiva if the benefit of the treatment offsets the risks. Sustiva can reduce the amount of Noxafil in the blood, making it less effective for treating infections.

Finally, the FDA warns that if Sustiva is taken with Selzentry (maraviroc), changes in the dose of one of the drugs may be necessary.

For more information, please see the FDA Web site.

A typical initial antiretroviral therapy regimen for HIV-positive patients who have not received therapy consists of two types of drugs: two NRTIs together with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor. Until now, it was unclear which two NRTIs are the most effective and safe.

This Phase 3 trial, known as study A5202, compared the efficacy and safety of two NRTI combinations, Viread and Emtriva versus Ziagen and Epivir, in previously untreated patients. These drugs were chosen because they have few side effects, are easy to take, and are potent anti-HIV agents.

Nearly 2000 patients participated in the trial. The patients were divided into four groups who received Viread and Emtriva or Ziagen and Epivir along with either Norvir (ritonavir)-boosted Reyataz (atazanavir), a protease inhibitor, or Sustiva (efavirenz), an NNRTI.

Among the 797 patients who had high viral loads at the start of the study, changes in the number of CD4 cells, a type of white blood cell that helps the body battle infection, was not significantly different between the two treatment groups.

However, 14 percent of patients in the Ziagen and Epivir group were unable to maintain viral suppression, compared to only 7 percent of the Viread and Emtriva group. Patients receiving Viread and Emtriva were also able to maintain viral suppression longer.

Results also showed that the combination of Viread and Emtriva was safer, with 20 percent experiencing serious side effects compared to 33 percent of those taking Ziagen and Epivir.

These results will strengthen recommendations by the United States Department of Health and Human Services that list Viread and Emtriva as the preferred NRTI combination for HIV-positive individuals starting antiretroviral therapy for the first time.

The AIDS Clinical Trials Group conducted this study with funding from the National Institute of Allergy and Infectious Diseases, a branch of the National Institutes of Health, with additional support from the General Clinical Research Center.

For more information, please read about the study on the U.S. Clinical Trials Web site or in the New England Journal of Medicine (abstract). Treatment guidelines can be found on the Department of Health and Human Services Web site.

Patients taking protease inhibitors or nucleoside reverse transcriptase inhibitors are at a higher risk of body fat redistribution and heart disease, according to an article published in the New England Journal of Medicine.

Body fat redistribution was evident in 20 to 35 percent of patients after one to two years on antiretroviral medication. Typically, fat accumulates in the mid-section or fat is lost from the face and limbs. Some patients may experience both symptoms. Sex, age and race have been shown to affect the severity. The study showed that fat accumulation was more frequent in women.

Increased levels of fat can accumulate in organs and the blood, increasing the risk of heart disease and diabetes.

The study also showed that older age and lower CD4 count may account for more noticeable fat loss from the body. CD4, or white blood cell count, is typically lower in those with HIV.

Antiretroviral medication is typically given in a combination with three or more other drugs, known as highly active antiretroviral therapy (HARRT). There are currently seven different classes of antiretroviral drugs, each producing a unique set of potential side effects.

The three classes that are most commonly prescribed are nucleoside reverse transcriptase Inhibitors (NRTIs), protease inhibitors, and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Each class of drugs works to target a different part of the HIV replication lifecycle.

During infection, HIV targets CD4 cells by programming these cells to carry out replication of the virus.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

NRTIs work to inhibit the conversion of RNA (the genetic material of viruses) to DNA. This conversion is necessary for the virus to infect CD4 cells. This class of drugs mimics protein building blocks that convert RNA to DNA and thereby inhibits its conversion by the virus. By preventing this process, new viral cells cannot be produced.

Common drugs in this class include zidovudine (Retrovir), Epzicom (abacavir/lamivudine) and Combivir (zidovudine/lamivudine).

According to HIV InSite, a project by the University of California San Francisco, the most common side effects with these drugs are acidosis, hepatic steatosis and body fat redistribution (as shown in the study by the New England Journal of Medicine).

Acidosis is a decrease in the pH of the blood. Respiratory acidosis, which is an increase of carbon dioxide in the blood, can also occur. This can be potentially dangerous for several reasons, including inadequate delivery of oxygen through out the body. Symptoms can include increased heart rate, shortness of breath and headaches.

Mild acidosis occurs in 10 to 40 percent of patients on antiretroviral therapy, according to AIDSMap, a non-profit organization in England.

Hepatic steatosis is when fat accumulates in the liver. Often, there are no symptoms from this occurrence. If the condition is detected early on, liver damage does not normally occur.

Side effects of Epzicom include a rash in about 50 percent of people, fever, nausea, vomiting and headache. Zidovudine has been shown to cause fatigue, nausea and headache, which normally subside after two to four weeks. Hyperpigmentation, or darkening, of the skin and nails can also occur. Combivir, which has active ingredients from both zidovudine and Epzicom, can produce similar side effects.

Protease Inhibitors

Protease inhibitors work to block the enzyme protease from cleaving protein segments in cells infected with HIV. Without the ability to cut, CD4 cells cannot produce new viruses. All protease inhibitors have gastrointestinal side effects.

Common drugs in this class include Norvir (ritonavir), Kaletra (lopinavir/ritonavir), and Prezista (darunavir).

Side effects may include accumulation of fat in the blood, diabetes and body fat redistribution problems. It also may increase the risk of bleeding in hemophiliacs (individuals who have an inability to form blood clots), according to HIV InSite.

According to AIDSMap, a study in Australia showed that 83 percent of patients taking this class of drugs experienced fat distribution changes. Eleven percent of patients had severe changes.

Prezista has been shown to cause rash and elevation of liver enzymes. Norvir and Kaletra frequently cause nausea, vomiting and diarrhea. Norvir can also have significant interactions with other medications.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

NNRTIs are similar to NRTIs in that they also affect the conversion of RNA to DNA. However, instead of mimicking protein building blocks, NNRTIs bind directly to the enzyme reverse transcriptase and therefore does not allow DNA to be formed.

Common drugs in this class include Rescriptor (delavirdine), Sustiva (efavirenz) and Viramune (nevirapine).

HIV InSite listed rash and toxic epidermal necrolysis, or cell death to the top layer of skin, as frequent side effects.

Rescriptor is less potent than other drugs in this class and therefore is not as commonly used as Sustiva or Viramune. It has been shown to cause nausea and vomiting. Side effects of Sustiva include drowsiness, confusion, abnormal dreams and abnormal levels of fat in the blood (which can lead to heart problems). Viramune has been shown to cause rash and liver failure.

Dealing With Side Effects

Continuation of some form of drug therapy is the best way to prevent HIV from developing into AIDS. However, certain side effects may be severe enough to warrant discontinuation or alteration of medications.

Dietary changes, exercise and cholesterol-lowering medications may be used to counteract concerns of heart disease in patients taking protease inhibitors or nucleoside reverse transcriptase inhibitors. In people with prior elevated risks for heart disease, a physician may have other recommendations, such as the use of a different class of drugs.

Symptoms of nausea, vomiting and diarrhea should be discussed with a physician. These could be signs of liver damage. In some cases, symptoms will subside or a physician may decide to change medication.

Body fat redistribution can be treated in several ways. Dietary changes or certain medications such as Glucophage (metformin) may be ordered for those who have fat accumulation in their body. For those who appear to be losing fat, injections of human growth hormone may be given.

As always, side effects that do not subside should be discussed with a physician to determine what necessary actions should be taken.

For more information on the heart disease and fat abnormalities, visit the article in the New England Journal of Medicine.

HIV is a retrovirus because it contains genetic information in the form of RNA. When HIV infects a human cell, it uses an enzyme called reverse transcriptase to convert the single stranded viral RNA to double stranded viral DNA. The viral DNA is then integrated into the host cell’s DNA and is able to go through cellular processes, such as transcription and translation, which allow it to replicate. RTIs are used to inhibit reverse transcriptase’s enzymatic function, thus preventing HIV replication.

There are three different types of RTIs:

Nucleoside Analog Reverse Transcriptase Inhibitors (NARTIs or NRTIs)

NRTIs were the first class of antiretroviral drugs developed. They are analogues of the normally occurring deoxynucleotides, molecules that make up the structural units of RNA and DNA, needed to synthesize the viral DNA. The only difference between NRTIs and deoxynucleotides is that NRTIs are missing a hydroxyl group, an oxygen atom bonded to a hydrogen atom. NRTIs compete with the normal deoxynucleotides for a position in the growing chain of viral DNA. When NRTIs are incorporated into the viral DNA, the missing hydroxyl group inhibits DNA synthesis from properly occurring, which is called chain termination. Thus, NRTIs are referred to as competitive substrate inhibitors because they bind to reverse transcriptase, the enzyme, in order to prevent the binding of the normal deoxynucleotides, the substrate.

Some NRTIs include zidovudine (Retrovir), didanosine (Videx), stavudine (Zerit), and Epivir (lamivudine).

Nucleotide Analog Reverse Transcriptase Inhibitors (NtARTIs or NtRTIs)

NtRTIs were the second class of antiretroviral drugs developed. Normally, nucleoside analogs are converted into nucleotide analogs by body processes. Thus, taking nucleotide analogs eliminates the conversion and goes directly to the inhibiting process. NtRTIs follow the same method of competitive substrate inhibition as NRTIs.

An example of an NtRTI is Viread (tenofovir).

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

NNRTIs were the third class of antiretroviral drugs developed. NNRTIs are non-competitive inhibitors of reverse transcriptase. They work by binding to a different site compared to the NRTI or NtRTIs and are not incorporated into the viral DNA. Instead, they inhibit the movement of proteins that are essential to reverse transcriptase’s function in carrying out DNA synthesis.

Some NNRTIs include Sustiva (efavirenz), Viramune (nevirapine), Rescriptor (delavirdine), and Intelence (etravirine).