Truvada For Prevention Of HIV Makes Time Magazine’s “Top 10 Medical Breakthroughs” For 2011 – Results from several studies showing that a daily dose of the antiretroviral Truvada (emtricitabine/tenofovir) can reduce the risk of HIV infection by 60 percent to 90 percent were declared one of the top 10 medical breakthroughs of 2011 by Time Magazine. The magazine noted that if the antiretrovirals were made widely available they could help curb the HIV/AIDS epidemic. The primary study, HPTN 052, was also chosen by Science Magazine as “2011 Breakthrough of the Year.” Gilead Sciences, which makes Truvada, applied for FDA approval to market the drug as an HIV prevention measure in December (see related AIDS Beacon news). However, Bloomberg noted that the drug costs $12,000 per year and has side effects, both of which may prevent widespread implementation. For more information, please see the articles in Time Magazine, Science Magazine, and Bloomberg.

Physicians Caution That Certain Anti-Seizure Drugs May Interfere With Antiretrovirals – New guidelines from American Academy of Neurology warn that certain anti-seizure medications, such as those taken to treat epilepsy, may interact with antiretroviral medications for HIV/AIDS. For example, the guidelines note that valproic acid (Depakote, Depakene) may increase the concentration of zidovudine (Retrovir) in the blood, increasing the risk of toxicity and side effects. Several anti-seizure medications also may interact with Norvir (ritonavir)-boosted Reyataz (atazanavir) and Kaletra (lopinavir/ritonavir). The guidelines recommend that people with HIV and seizure disorders share with their clinician what medications they are taking so that drug types and dosages can be adjusted if needed. For more information, please see the guidelines (pdf) or the patient information guide (pdf) at the American Academy of Neurology website.

The authors noted that their results provide further justification for listing Truvada as a preferred combination regimen and Combivir and Epzicom as alternative regimens.

However, the study appears to be based on the separate costs of Truvada and Sustiva pills rather than Atripla, the once-daily pill that combines Truvada and Sustiva. The study also did not take into account the possibility of generic Combivir, which was approved by the U.S. Food and Drug Administration last month (see related AIDS Beacon news) and is expected to be available later this year.

The study authors also pointed out that some studies have suggested that Truvada may not be as effective for people who start treatment at lower viral loads, in which case Truvada may not be as cost-effective for these patients.

According to the study authors, rising drug costs and longer life expectancies for people with HIV mean that the costs of antiretroviral therapy have now become an important consideration.

In addition to the direct cost of the drugs, total health care costs are affected by the efficacy of a person’s first-line therapy and his or her long-term health. Low viral loads (amount of HIV in the blood) and high CD4 (white blood cell) counts, which are achieved with treatment, prevent disease progression and other illnesses associated with HIV.

First-line therapies are also more likely to have easier dosage schedules and are usually less expensive than later antiretroviral regimens. As a result, the longer a person can stay on first-line therapy, the lower his or her long-term health costs are expected to be.

Currently, U.S. treatment guidelines for HIV recommend that first-line therapy consist of two nucleoside reverse transcriptase inhibitors (NRTIs) plus at least one drug from another antiretroviral class. Truvada (emtricitabine/tenofovir), a combination of two NRTIs, is listed as the preferred combination of NRTIs, and the non-nucleoside reverse transcriptase inhibitor Sustiva (efavirenz) is listed among the preferred drugs to use in combination with NRTIs..

The two-NRTI combination pills Combivir (lamivudine/zidovudine) and Epzicom (abacavir/lamivudine) are listed as alternatives to Truvada.

In this study, the authors compared the cost-effectiveness of Truvada, Combivir, and Epzicom, each used with Sustiva, as first-line treatments in HIV-positive adults.

The authors developed a computer model for each first-line therapy that included annual drug costs, drug efficacy, medical costs related to treatment of side effects and HIV-related illnesses, the cost of switching antiretroviral regimens when a first-line regimen is no longer effective, and the estimated costs of second- and third-line treatment regimens based on current treatment guidelines.

Information such as drug efficacy, side effects, and failure rates were obtained from a 144-week study of Sustiva plus Truvada or Combivir and a 48 week study of Sustiva plus Combivir or Epzicom.

Results showed that Truvada was the most cost-effective NRTI combination for a first-line treatment regimen, with patients predicted to remain on the drug for almost eight years. Estimated lifetime costs for HIV treatment for people starting with Truvada plus Sustiva were $747,327.

Patients taking Epzicom were predicted to remain on the therapy for six years and accrue lifetime costs for HIV treatment of $777,090, and patients on Combivir were predicted to remain on it for almost six years with lifetime costs of $778,287.

The lower overall cost for Truvada was primarily a result of its greater efficacy, which delayed disease progression and allowed patients to remain on treatment longer.

For more information, please see the study in Value in Health (abstract).

The generic drug will be made by Teva Pharmaceuticals.  According to the company, the generic version will be available as of the fourth quarter of this year.  Since Teva is the first company to apply for FDA approval of the generic form of Combivir, Teva will be given 180 days to exclusively market the generic drug,  after which other generic versions can be marketed.

The branded drug Combivir is marketed by ViiV Healthcare, a joint venture of GlaxoSmithKline and Pfizer.

For a list of other approved generic anti-HIV medications, please see the FDA website.

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.

The guidelines include updates on preferred regimens for prevention of HIV transmission during pregnancy.

According to the report, fewer than 200 children are now born with HIV in the United States each year, as a result of efforts to limit mother-to-child transmission.

Transmission of HIV from a pregnant woman to her baby can occur during pregnancy, labor, or while breastfeeding after the baby is born. To prevent this, women are usually treated with antiretrovirals throughout the pregnancy and are told not to breastfeed their babies.

In this latest report, the NIH now recommends that pregnant women with HIV who are not already taking antiretrovirals start taking them sooner than previously suggested. The NIH suggests initiating treatment after the first trimester, and no later than 28 weeks into the pregnancy.

The guidelines also recommend pregnant women take a combination regimen consisting of at least three drugs, preferably two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor.

The recommended NRTI regimen is Combivir (zidovudine/lamivudine), based on clinical trials demonstrating its effectiveness.

The recommended NNRTI is Viramune (nevirapine), although only in women with CD4 cell counts of less than 250 cells/mm3 unless the benefits outweigh the risk of potential liver toxicity. Women already taking Viramune may continue during pregnancy.

The recommended protease inhibitor regimen is Kaletra (lopinavir/ritonavir). Alternative protease inhibitors include Norvir (ritonavir) in combination with Invirase (saquinavir), Crixivan (indinavir) or Reyataz (atazanavir).

Several treatments are not recommended for part or all of the pregnancy:

• The combination of stavudine (Zerit) and didanosine (Videx) are not recommended since they may cause serious side effects, including liver failure, in pregnant women.

• Sustiva (efavirenz) should not be taken in the first trimester of pregnancy because of possible harm to the baby. Sustiva is also an ingredient in Atripla (efavirenz/emtricitabine/tenofovir).

• Viread (tenofovir) should only be used when there is intolerance or resistance to zidovudine (Retrovir) or if the pregnant woman has hepatitis B because it may harm the baby. Viread is also an ingredient in Atripla and Truvada (emtricitabine/tenofovir).

• There is not yet enough data on Intelence (etravirine), Prezista (darunavir), Lexiva (fosamprenavir), Aptivus (tipranavir), Fuzeon (enfuvirtide), Selzentry (maraviroc), or Isentress (raltegravir) to recommend their use in pregnancy, although in some cases they may be used if other drugs are not well tolerated.

Prevention of mother-to-child transmission in HIV-positive women with hepatitis B (HBV) is also discussed. Treatment options depend on whether the mother requires anti-HIV treatment for her own health, anti-HBV treatment, or both.

The NIH also reaffirmed its recommendation that HIV-positive women should avoid breastfeeding. Although clinical trials in Africa have shown that antiretrovirals reduce the chances of transmitting HIV through breastfeeding, there is still a risk.

Since women in the U.S. have a safe, viable alternative to breastfeeding – formula feeding – the NIH strongly discourages HIV-positive women from breastfeeding.

After the baby is born, antiretroviral treatment of the infant is usually continued to ensure infection does not occur. The recommended treatment is zidovudine for six weeks after birth. In the new guidelines, the NIH warns that combining zidovudine with other treatments is not well-studied and should be done with caution.

Both Norvir and Kaletra have been associated with heart block, a problem with the heart’s electrical system, in babies, and therefore require especially close monitoring if used in infants.

Finally, food pre-chewed by HIV-positive caregivers should not be given to infants since this potentially increases the risk of HIV transmission.

The NIH welcomes feedback on the guideline revisions. Comments should be sent to ContactUs@aidsinfo.nih.gov with the subject line “Perinatal Comments” by June 7, 2010.

For more information, please see the complete guidelines at the NIH (pdf) website.

Combivir (zidovudine/lamivudine) is a combination therapy that includes zidovudine (Retrovir) and Epivir (lamivudine). Both zidovudine and Epivir are nucleoside reverse transcriptase inhibitors (NRTIs), which act as fake versions of the building blocks HIV needs to replicate. Zidovudine used in combination with Epivir is often part of the first line of antiretroviral therapy for HIV patients.

Lipodystrophy, abnormal growth or change in fat tissue, is one of the most common and potentially serious side effects associated with HIV treatment. Two different types of lipodystrophy are often present in HIV patients, lipoatrophy and lipohypertrophy. Lipoatrophy, or limb fat loss, is a decrease in fat tissue in a localized area such as the legs, arms, buttocks, or face. Some other signs of lipoatrophy could include veins protruding in those areas and sunken cheeks in the face. Lipohypertrophy, in contrast, is an abnormal increase in fat. In patients receiving treatment for HIV, lipohypertrophy commonly occurs around the stomach, and can also lead to increased fat tissue in the breasts and in the back of the neck or shoulders.

Previous studies have shown that lipodystrophy is associated with HIV treatment with stavudine (Zerit), another NRTI. This study suggests that other NRTIs may also be associated with lipodystrophy.

The study was conducted with 50 HIV-infected men who were undergoing antiretroviral treatment for the first time. Each participant was randomly assigned one of two different therapy treatments. The Combivir-containing therapy included Combivir and Kaletra (lopinavir/ritonavir). Kaletra is a combination therapy using two protease inhibitors (PIs) that disable a protein necessary for HIV replication. The Combivir-free treatment included Kaletra and Viramune (nevirapine), a non-nucleoside reverse transcriptase inhibitor (NNRTI), which works by blocking the action of reverse transcriptase, an essential protein for HIV replication.

The study was conducted for 24 months, and results showed that the Combivir-containing therapy led to increased lipoatrophy and lipohypertrophy compared to the Combivir-free therapy. Since no differences in effectiveness or safety were found between the two treatments, the researchers recommend that Combivir no longer be considered as a first-line antiretroviral therapy for treatment of HIV infections.

For more information about the study, see the original article at the PLoS Hub Web site.