Two of the studies focused on methods to completely eliminate HIV from the body. More specifically, they targeted latent HIV – HIV that lies dormant in infected cells and can start multiplying again if antiretroviral therapy is stopped.

Latent HIV is difficult to get rid of because after infection, the virus actually inserts its own DNA into a cell’s normal DNA sequence. Antiretrovirals can prevent the virus from using this DNA to make more of itself, but they can’t remove the virus DNA once it has been inserted.

As a result, HIV can hide out in an infected person’s DNA indefinitely, even if they are taking antiretrovirals. This type of HIV is called latent HIV and is the reason HIV cannot be cured with current treatments.

Two new studies presented Monday focused on targeting and removing latent HIV. In both studies, researchers created treatments that were shown in animal tests to reduce the amount of latent HIV in the body. In one case, however, the results were only temporary.

Three other studies showed positive preliminary results for new antiretroviral drugs: four new protease inhibitors, and two new integrase inhibitors. The new drugs show promise, but are still in early stages of development.

New Treatments To Remove Latent HIV From Cells

Two studies were presented showing preliminary research on new treatments to remove latent HIV from cells.

In the first study, a team of German and Swiss researchers created an artificial protein that cuts latent HIV DNA out of cells and prevents virus replication in mice.

Unlike normal antiretrovirals, the new protein is able to find virus DNA inside a cell’s DNA and cut it out of the sequence. It can also act like a regular antiretroviral and prevent the virus from multiplying.

In this study, the investigators modified either human adult CD4 (white blood) cells or human blood stem cells so that they could produce the artificial protein. They then transplanted these cells into mice to see if the protein would effectively remove latent HIV DNA or have antiretroviral activity.

The researchers found that the protein caused a substantial decrease in HIV viral loads (amount of HIV in the blood) and also protected CD4 cells in the mice, with no toxicity.

As a result of these promising results, the scientists recommend further study of the protein to see if it could be used as a novel treatment for HIV in addition to traditional antiretrovirals.

In the second study, Italian and American researchers looked at Gar1041, an experimental leukemia drug, in combination with antiretroviral therapy to see if it could reduce the amount of latent HIV DNA in monkey cells.

GAR1041 is a new type of experimental drug called an epigenetic drug. Epigenetic drugs are used to turn genes on and off and have mostly been studied in cancer cells. However, the researchers thought they might also be useful to fight latent HIV.

Within one month of treatment with Gar1041 plus antiretroviral drugs, the researchers found that the amount of latent HIV in the monkeys significantly decreased. The drop was not observed in monkeys receiving only antiretroviral therapy.

However, the concentrations of latent HIV rebounded after two months of therapy. The researchers concluded that their study shows latent HIV can be reduced using drug treatments, which is promising. However, further research would be necessary to permanently reduce latent HIV and keep it from rebounding.

Improved Therapies: Novel Protease And Integrase Inhibitors

A joint effort between Japanese and American scientists yielded four new protease inhibitors that were highly effective against drug-resistant HIV in laboratory tests.

Protease inhibitors, such as Kaletra (lopinavir/ritonavir) or Prezista (darunavir), work by blocking a virus protein called protease, which then prevents virus proteins from assembling properly.

The four new drugs developed by the Japanese-American team were found to be highly effective protease inhibitors in the laboratory. One of the drugs was more powerful than Prezista. As a result, they will be studied further as potential drugs to fight resistant HIV strains.

Another study, presented by researchers at GlaxoSmithKline, showed results for a potential new integrase inhibitor.

Integrase inhibitors are a relatively new class of drugs. They work by blocking the protein the virus uses to insert its DNA into the DNA of a healthy cell, thus preventing HIV from replicating.

In 2007, Isentress (raltegravir) was the first integrase inhibitor to receive approval from the United States Food and Drug Administration. Soon after its introduction, HIV resistance against Isentress developed.

The new integrase inhibitor, S/GSK1265744, was effective in laboratory tests against HIV virus isolated from patients showing resistance to Isentress. As a result, it could be used to treat HIV that is resistant to Isentress.

Finally, in another study, Belgian and Swiss scientists presented a new type of integrase inhibitor called LEDGINs. LEDGINs work slightly differently than Isentress and were very effective in the laboratory against Isentress-resistant HIV.

Although still in the early stages of development, the drugs show promise as new treatments for HIV. Further studies to assess their effectiveness are currently underway.

For more information, please see the AIDS 2010 conference website.

The studies, which yielded mostly positive results, illustrate the growing variety of treatment and medication options for people with HIV.

The three studies involving new treatment regimens all use Isentress (raltegravir), an integrase inhibitor approved by the United States Food and Drug Administration in 2007.

Integrase inhibitors are a relatively new class of drugs. They work by blocking the protein the virus uses to insert its DNA into the DNA of a healthy cell, thus preventing HIV from replicating. Isentress is currently the only approved integrase inhibitor.

In one study, Isentress was evaluated in a simplified two-drug combination treatment with Kaletra (lopinavir/ritonavir), a protease inhibitor. Two other studies tested the efficacy of replacing protease inhibitors with Isentress.

Protease inhibitors often increase cholesterol levels, which increases a patient’s risk of developing heart disease. Researchers predicted that switching to Isentress would reduce the risk of heart disease.

In all three studies, the new regimens involving Isentress have so far successfully suppressed the virus, produced few side effects, and decreased cholesterol levels in people with HIV.

The other two studies tested new drugs in Phase 2 development. Both drugs have demonstrated short-term efficacy and safety. One of the drugs is a CCR5 antagonist, like Selzentry (maraviroc). The other is a new integrase inhibitor, like Isentress.

Study Of The Two-Drug Combination Of Kaletra And Isentress

A 96-week-long Phase 3 study is currently assessing the safety and efficacy of taking Kaletra with Isentress. The new combination is compared to Kaletra plus Truvada (emtricitabine/tenofovir), which contains two reverse transcriptase inhibitors.

The study participants are all treatment-naïve, meaning they have not taken antiretroviral medications before.

The 48-week study results revealed that the combination of Kaletra and Isentress suppressed the virus as effectively as Kaletra plus Truvada. The treatment was well tolerated, and the most common side effects were diarrhea and high cholesterol. High cholesterol has been associated with protease inhibitors like Kaletra.

Researchers concluded that the two-drug combination of Kaletra and Isentress is promising as an effective treatment for HIV.

The Kaletra/Isentress treatment combination is unusual because it consists of only two medications and does not involve reverse transcriptase inhibitors.

The current regimen for people with HIV who are beginning treatment consists of three ART drugs: two reverse transcriptase inhibitors (such as those contained in Truvada) and a third drug, usually a protease inhibitor (such as Kaletra).

However, reverse transcriptase inhibitors have been associated with lipodystrophy, a side effect in which fat gets redistributed abnormally on the body. Changes in fat distribution can lead to changes in body shape and can also cause cardiovascular disease. As a result, researchers have experimented with antiretroviral regimens, such as the Kaletra/Isentress combination, that do not contain reverse transcriptase inhibitors.

The trial is ongoing but is no longer recruiting participants.

Replacement Of Protease Inhibitors With Once Or Twice Daily Isentress

A Phase 4 study evaluated the switch from a protease inhibitor regimen to a once or twice daily dosage of Isentress, an integrase inhibitor. The trial followed 222 participants with HIV for 24 weeks.

Researchers hoped switching to Isentress would lower participants’ cholesterol levels. In addition, Isentress is currently given twice daily. If effective, a once daily dosage would decrease treatment burdens for patients.

Researchers measured the effectiveness of the once daily dosage and monitored the patients’ cholesterol levels after switching from the protease inhibitor regimen.

Replacing the protease inhibitor regimen with Isentress was effective in all patients except in those who had previously demonstrated resistance to reverse transcriptase inhibitors. The once daily dosage of Isentress performed slightly worse than twice daily dosing.

In addition, as predicted, the patients’ cholesterol levels were significantly lowered after the switch to Isentress.

The study, sponsored by Hospital Carlos III in Madrid, is ongoing and currently recruiting participants.

Replacement Of Protease Inhibitors With Isentress

A 48-week Phase 3 study has been completed that compared patients taking protease inhibitors to those who switched to Isentress, an integrase inhibitor. The participants in both groups of the study started with low viral loads (amount of HIV in the blood).

At 48 weeks, the two regimens were similarly effective at maintaining low viral loads. Additionally, switching to Isentress effectively lowered cholesterol levels in patients.

There was a slight increase in the number of patients experiencing side effects. Side effects that led to treatment discontinuation occurred in 4 percent of patients treated with the Isentress regimen versus 2 percent of those on the protease inhibitor regimen.

Study Of A New CCR5/CCR2 Antagonist, TBR-652

Tobira Therapeutics completed a Phase 2 study of a possible new treatment, TBR-652, a dual CCR5/CCR2 antagonist.

CCR5/CCR2 antagonists work by blocking the CCR5 and CCR2 proteins on the outside of immune cells. When these proteins are blocked, the drug prevents HIV from attaching to and infecting the cells. Selzentry is the only currently approved CCR5 antagonist.

The study tested the antiviral ability, safety, and tolerability of TBR-652 taken once daily for 10 days. This is the first study of TBR-652 that has tested the medication on people with HIV.

A previous Phase 1 trial showed that the drug was well tolerated in HIV-negative subjects. The 54 HIV-positive participants in the Phase 2 trial also tolerated the drug well; there were no serious side effects or deaths.

Additionally, when TBR-652 was taken as the sole antiretroviral medication, the researchers reported significant antiviral activity, as measured by viral load.

“Our unique, dual CCR5/CCR2 investigational drug may provide a new strategy that would complement the well-established benefits of currently available virus-suppressing treatments for HIV,” said David Martin, Senior Vice President of Drug Development and Regulatory Affairs for Tobira Therapeutics in a press release.

The drug will require further trials at longer durations to determine whether it is a viable treatment option.

Study Of A New Integrase Inhibitor, S/GSK1349572

Shionogi-GlaxoSmithKline Pharmaceuticals is testing a new integrase inhibitor, S/GSK1349572, in an ongoing 24-week Phase 2b study on patients who are resistant to the integrase inhibitor Isentress.

The results through Day 11 have revealed that most of the subjects have tolerated the new drug well. The most commonly observed side effects were diarrhea and insomnia.

The study continues to observe the efficacy of the new integrase inhibitor against a variety of HIV-variants resistant to Isentress.

The trial is currently recruiting participants.

For more information, please see the AIDS 2010 conference website.

Integrase inhibitors belong to a class of anti-HIV drugs that work by inhibiting HIV replication, thereby preventing viral DNA from invading the genetic material of T-cells (healthy immune cells). Because integrase inhibitors have a different mechanism of action from other anti-HIV drugs, patients will have more options for viral suppressants, thereby making their treatment more effective and less vulnerable to developing resistance.

The study was a double-blind, randomized, placebo-controlled study of INI divided into three parts: single (Part A) and multiple (Part B) oral dose of increasing increments in 48 healthy subjects and a multiple oral dose study (Part C) in 11 HIV-infected patients.

In Part A, two groups were given alternating doses of INI suspension or placebo. In Part B, three groups were given INI suspension or placebo once daily for 14 days. In Part C, subjects were given six 5mg INI tablets or placebo once daily for 10 days.

Results in Part C showed a reduction in viral load of HIV infected patients. Additionally, 88 percent of the subjects receiving INI were able to reach undetectable levels of HIV in their level (below 50 copies/mL) by Day 14. Pharmacokinetic data from healthy subjects and INI-naïve HIV subjects showed that INI has a long plasma half-life of 30 hours (how long INI is able to stay in the plasma), lower variability, was able to reach therapeutic concentrations with a low dosage.

Overall, INI was well tolerated in both healthy and HIV-infected subjects, with mild side effects reported, the most common being headaches. Additional studies are needed in order to determine the safety and efficacy of INI as an anti-viral medication for HIV-patients.

For more information, please see Shionogi-GlaxoSmithKline Pharmaceuticals’ press release.

D.C. Public School System Offers STD Testing To High School Students: A report released today by the D.C. Appleseed Center for Law and Justice commended the recent D.C. school board decision to offer tests for sexually transmitted diseases (STD) to all public high school students this fall. A recent pilot program found that 11 percent of students tested positive for an STD, which increases the likelihood of HIV transmission during sexual contact. AIDS activists see the decision as an effort to arrest the city’s AIDS rate, which is the highest in the nation. For more information, please see the D.C. Appleseed report and the related Washington Post article.

Study Shows VivaGel Protects Against HIV And HSV Infection: A recent clinical study conducted in Melbourne, Australia demonstrated the anti-HIV and anti-HSV (herpes simplex virus) properties of VivaGel, a Starpharma product. VivaGel is a vaginally administered microbicide that blocks sexually transmitted diseases. It is currently in Phase 2 clinical trials in the U.S. The recent study suggests VivaGel retains its activity following vaginal administration and is active longer than expected. For more information, please see the Starpharma press release (pdf).

Study Reveals Isentress Is A More Effective Treatment Than Sustiva In Treatment-Naïve Patients: In a recent study published in The Lancet, the new antiretroviral Isentress (raltegravir) proved to be more effective in first-line therapy and faster in suppressing HIV replication than Sustiva (efavirenz), with fewer side effects. Isentress is an integrase inhibitor manufactured by Merck. For more information, please see the study in The Lancet (abstract) or read the related MedPage Today article.

In HIV replication, integrase allows the virus to insert, or “integrate,” its genetic material into the host cell’s DNA. As a result, the infected CD4, or “T-helper,” cell produces copies of the virus instead of new proteins for the cell’s own use.

This stage of HIV infection allows the host cell to create more copies of the virus to spread and infect other healthy cells.

Though researchers do not entirely understand how the enzyme acts, managing integrase through drug therapy has promising results thus far. The therapy is known to suppress and reduce a patient’s “viral load,” or the number of HIV copies in one milliliter of blood, because infected cells do not replicate more copies of the virus.

INIs are usually used in combination with other antiretroviral drugs – which target viruses like HIV that make copies of themselves in host cells. Unlike the majority of antiretroviral drugs, INIs are seen as a last resort to patients who have developed resistance to drugs.

Most INIs are taken orally in the form of pills, and long-term side effects of the drugs are still being studied. Specialists rarely prescribe INIs for patients who have not started antiretroviral treatments or patients who are responsive to other drugs.

The first FDA-approved INI was Isentress (raltegravir) in 2007. Some of the reported side effects of the drug were diarrhea, nausea, headache, and fever. In more severe cases, patients reported rash, Stevens-Johnson syndrome (a heightened mucous and skin reaction to a medication or infection), and depression.

Some INIs were discontinued during Phase 2 trials because of their toxicity – or degree to which a substance can harm an organism – in dogs. Elvitegravir, also known as “GS-9137,” is currently in Phase 3 trial by Gilead Sciences, Inc.