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• DRUGS IN DEVELOPMENT
Integrase Inhibitor Shines Again in Treatment-Experienced Patients
One of the most promising antiretrovirals in development has a new name -- and new, highly promising study results to accompany it. Raltegravir is the newly minted generic name (and Isentress is the proposed brand name) for the integrase inhibitor MK-0518. In research presented at CROI 2007, an impressive 79% of treatment-experienced patients who received MK-0518 as part of an optimized salvage regimen achieved a viral load of less than 400 copies/mL by week 16 -- and adverse effects were similar to patients receiving a placebo. The Body PRO's Edwin DeJesus, M.D., reports.  Click Here
For more study analysis straight from the mouths of the investigators, listen to the podcast of a press conference with MK-0518 researchers David Cooper and Roy Steigbigel. The Body PRO also spoke with Dr. Steigbigel about the likelihood that MK-0518 will be covered by drug plans in the United States; you can listen to a podcast of that interview as well.
Maraviroc Continues to Impress in Clinical Trials
It has been a rocky road for the development of CCR5 antagonists: Unforeseen safety issues caused two major clinical trials of aplaviroc and vicriviroc to be halted prematurely. However, one CCR5 antagonist is still going strong: CROI 2007 saw the release of encouraging Phase 3 safety and efficacy data on maraviroc (UK-427,857), which may be inching closer to U.S. approval. The Body PRO's Graeme Moyle, M.D., reports from CROI 2007 on interim results from MOTIVATE 1 and MOTIVATE 2 -- two large, randomized trials of maraviroc conducted in treatment-experienced patients. Click Here
You can also listen to the podcast or read the transcript of our interview with Roy Gulick, one of the investigators in the maraviroc studies. Dr. Gulick discusses the study results and comments on a link researchers found last year between CCR5 inhibitor use and the severity of illnesses such as West Nile virus.
New NNRTI Advances Through Dose-Finding Study
TMC278, a next-generation NNRTI, is making its way through Phase 2b development. A dose-finding study presented at CROI 2007 shows that all tested doses of TMC278 exhibited similar antiretroviral activity to that of its fellow NNRTI efavirenz (Sustiva, Stocrin), through 48 weeks of treatment. The Body PRO's Graeme Moyle, M.D., reports. Click Here
GS 9137: Yes, There's an Integrase Inhibitor Other Than MK-0518
Each year, the Conference on Retroviruses and Opportunistic Infections -- as the first major HIV conference of the year -- gives the HIV health care community a chance to take stock of the antiretroviral pipeline. This year's crop includes some particularly intriguing prospects, including several antiretrovirals you may not yet have heard of. The Body PRO's Edwin DeJesus, M.D., reports on one of these drugs: the integrase inhibitor elvitegravir, formerly known as GS 9137. Click Here
More Tantalizing Evidence Tentatively Supports Interleukin-2 for Treatment-Naive Patients
It's the immune-based therapy drug that refuses to die, but that has also never made it as a proven therapy: interleukin-2 (IL-2). For years, researchers have explored the CD4+ cell count-boosting effects of IL-2 and sought to define its potential role in HIV treatment. A substudy presented at CROI 2007 examined whether IL-2's immune-strengthening properties could help delay the commencement of HAART in treatment-naive patients. As with so many IL-2 studies in the past, the results appear somewhat positive -- but are they positive enough? The Body PRO's Keith Henry, M.D., reports. Click Here |
• HIV TREATMENT & PATIENT CARE
Rate of CD4+ Cell Count Decline Is Poor Predictor of HIV Disease Progression, Study Finds; Role of Viral Replication Reaffirmed
Contrary to prior belief, the rate of CD4+ cell count decline in untreated, HIV-infected individuals poorly predicts the risk of AIDS or death, new data indicates. Last fall, Benigno Rodriguez, M.D., stirred up controversy when he published a paper challenging the power of the rate of CD4+ cell count decline to predict the risk of AIDS or death. At CROI 2007, John Mellors, M.D. -- whose research established the power of CD4+ cell decline rate in the first place -- presented a key study that refuted his earlier work and supported Rodriguez’s recent findings. Mellors reported that baseline CD4+ cell count only predicted 1.4% of the subsequent CD4+ cell count decline in individuals, indicating that several other factors contribute to immunologic deterioration. In contrast, Mellors found that baseline viral load predicted 46.1% of the variability in the time to AIDS. “These results reaffirm the key role of viral replication, as reflected by viral load, in the pathogenesis of AIDS,” Mellors stated. Click Here
10% of Newly Infected Patients Have Drug Resistance, Study Finds
The latest U.S. HIV treatment guidelines urge resistance testing for all patients newly diagnosed with HIV -- even if antiretroviral therapy is not yet indicated. Why such urgency? New research presented at CROI 2007 drives the point home: An 11-state study in the United States found that more than 10% of recently infected patients had a strain of HIV that was resistant to at least one antiretroviral. The Body PRO's Mark Holodniy, M.D., reports. Click Here
Once-Daily Lamivudine + Nevirapine + Tenofovir Leads to High Failure Rates in Treatment-Naive Individuals
Although one NNRTI + two NRTIs is one of the basic formulas recommended for first-line therapy, not all variations of this combination fully suppress viral replication. So it is with the once-daily combination of lamivudine (3TC, Epivir) + nevirapine (Viramune) + tenofovir (Viread), according to a study presented at CROI 2007. The French DAUFIN study was designed to compare once-daily lamivudine + tenofovir + nevirapine versus twice-daily zidovudine/lamivudine (Combivir) + nevirapine in treatment-naive individuals, but was prematurely halted due to a high rate of virologic failure in the once-daily arm. Of the 36 individuals assigned to once-daily treatment, eight developed early virologic failure before week 12 and another individual experienced viral rebound after week 12 (total failure rate = 25% vs. 3% for the twice-daily arm). Although the reasons for failure are currently unclear, the emergence of NNRTI resistance mutations (i.e., K65R and Y181C/A) was quite common in those who failed treatment, as was the emergence of the M184V NRTI resistance mutation. Click Here
Surprise: Entecavir Active Against HIV as Well as HBV
Entecavir (Baraclude), a therapeutic agent for hepatitis B virus (HBV) that was believed to only be active against HBV, also shows activity against HIV, according to a study presented at CROI 2007. Moreover, the agent can apparently select for HIV resistance mutations. Researchers from Johns Hopkins University reported on three HIV/HBV-coinfected individuals taking entecavir monotherapy for HBV, but not currently on therapy for HIV, who showed at least a 1-log10 decline in HIV-1 RNA after beginning entecavir treatment. Two of these individuals later experienced HIV viral rebound, and one developed the M184V mutation in HIV, which confers high-level resistance to entecavir, as well as to lamivudine (3TC, Epivir) and emtricitabine (FTC, Emtriva). Based on the findings, “entecavir should not be used in HIV/HBV-coinfected individuals not on a fully suppressive HIV regimen without careful consideration of other options,” the Johns Hopkins researchers advised. Click Here
In an interview at CROI 2007, HIV researcher Marshall Glesby, M.D., spoke with The Body PRO about this study; you can listen to the podcast or read the transcript of that interview. (Dr. Glesby discusses entecavir toward the end of the interview.) For more information, you can also read the "Dear Health Care Provider" letter (PDF) released by the manufacturer of entecavir.
Lopinavir/Ritonavir Monotherapy Reserved for Select Patients
A growing number of studies show that maintenance monotherapy with lopinavir/ritonavir (Kaletra) may be fine for select patients, since the drug is generally associated with a low risk of virologic rebound and protease inhibitor resistance. However, it remains unclear whether this strategy can -- or should -- be applied in real-life clinical situations, particularly considering how much more tolerable NRTI-based therapy has become in recent years. The Body PRO's Paul Sax, M.D., reports from CROI 2007. Click Here |
• COMPLICATIONS IN HIV-INFECTED PATIENTS
Chewing the Fat Contributes to Dyslipidemia in HIV-Infected Individuals, Study Finds
Massachusetts General Hospital, Harvard Medical School, and the U.S. National Institutes of Health recently partnered to investigate the relationship between diet and lipid levels in HIV-infected individuals as compared with HIV-uninfected individuals. The findings, reported at CROI 2007, may be enough to make a nutritionist faint. Although both populations had similar demographic profiles and consumed about the same number of calories, HIV-infected individuals consumed significantly more total fat, saturated fat and cholesterol during the course of a day than HIV-uninfected individuals. What’s more, 76% and 50% of HIV-infected individuals consumed more than the U.S. recommended daily allowance of saturated fat and cholesterol, respectively -- proportions that were significantly higher than those seen in the HIV-uninfected population. Not surprisingly, hypertriglyceridemia was strongly associated with the intake of saturated fat among HIV-infected individuals. The investigators of this study remarked that “increased saturated fat intake should be targeted for dietary modification in this population.” Click Here
Non-Opportunistic Infections Have Grown More Prevalent Than OIs
Adverse events not typically associated with HIV now make up a majority of reported complications among HIV-infected people on treatment, according to a major study presented at CROI 2007. These non-opportunistic infections also do not decrease as quickly once antiretroviral therapy commences, the study found. As The Body PRO's Pablo Tebas, M.D., reports, these findings drive home two important points: One, suboptimal therapy should not be continued if other options are available that could lower viral load and increase CD4+ cell count. Two, physicians and patients alike should not assume that treatment initiation will, in and of itself, resolve health complications; illnesses among HIV-infected patients may require more specific attention. Click Here
Smoking Cigarettes May Increase Anal Cancer Risk for Men With HPV
Cigarette smoking appears to increase human papillomavirus (HPV) viral load in men with anal HPV, which may speed the development of squamous cell intraepithelial lesions, according to a German study presented at CROI 2007. The study found that smokers had higher rates of HPV infection, including cancer-associated HPV types, than non-smokers. It also noted that smokers had higher HPV viral loads than non-smokers, and that squamous cell intraepithelial lesions -- particularly high-grade lesions -- were likewise significantly more common among men who smoked. Click Here |
• HIV TRANSMISSION
49% of HIV Transmissions Involve a Recently Infected Partner, Study Says
Nearly one out of every two HIV transmissions occurs when the person transmitting HIV has been recently infected, according to a team of Canadian researchers led by Mark Wainberg of the McGill University AIDS Centre. The finding points to the importance of frequent HIV testing, as well as the use of methods to diagnose cases of acute infection. The medical community "must do a much better job of identifying recently infected people if we are to be able to counsel them to modify high-risk sexual behavior and desist from transmitting the virus," Wainberg said. Click Here
HIV Testing in Gay Bath Houses Reaches Underserved Men, Study Says
Many high-risk individuals do not seek out HIV testing and prevention services. In an effort to reach some of these underserved people, a group of New York University researchers began offering HIV tests at two bath houses in New York City. The researchers found that not only was it possible to provide HIV testing there, but that doing so offered health professionals a unique opportunity to do prevention work with men who do not access traditional HIV prevention and testing services. The bath house patrons were told that HIV testing was available at the venue once a week, but the bath house staff did not approach patrons to promote testing. Nonetheless, a total of 350 rapid HIV tests were performed on 292 men, many of whom had never received HIV testing before. Fifteen men tested positive for HIV during the study; none became overly distressed by the results of their rapid oral test and all returned for their confirmatory blood test results. The researchers concluded that the program was successful, and plan to offer HIV testing at both venues three times a week. Click Here
Latinos Overlooked When It Comes to HIV Testing, Study Finds
Many primary care providers in predominantly Hispanic areas in Los Angeles County do not routinely offer HIV testing to Latino patients, according to a study released by the University of California-Los Angeles' AIDS Institute. Out of 85 physicians, nurse practitioners and physician assistants surveyed -- all of whom practiced in areas with a Latino population of at least 50% -- only 41% said that they regularly offered their patients advice about sexually transmitted diseases, and just 36% had ordered more than 20 HIV tests in the preceding six months. Researchers believe that the lack of testing could be contributing to the increase of AIDS cases among Latinos in Los Angeles County. Click Here |
• HIV IN THE NEWS
Mailing Error Reveals Names of 53 California ADAP Patients
The California Department of Health Services inadvertently revealed the names and addresses of up to 53 residents enrolled in the state's AIDS Drug Assistance Program (ADAP) by mailing benefit notification letters to the wrong ADAP members. A newly hired clerk did not realize that the letters were personally addressed and put them into envelopes, adding mailing labels to each envelope without matching them to the letters. The department informed the ADAP enrollees of the error through certified mail and asked that incorrectly addressed letters be destroyed. A departmental spokesperson said that steps would be taken to ensure a similar mistake does not happen again. Representatives from local HIV organizations expressed disappointment, but indicated that the error was not cause for panic or indicative of a systemwide failure. Click Here |
• HIV OUTSIDE THE UNITED STATES
Discrimination Against MSM Worsens HIV Epidemic in Africa, Report Says
Governments throughout the world are being urged to break their silence about discrimination against homosexuals in Africa, in an effort to help curb the spread of HIV across the continent. A new report released by the International Gay and Lesbian Human Rights Commission (IGLHRC) says that, despite comprising a large proportion of the African HIV epidemic, men who have sex with men (MSM) are overlooked and unprepared for HIV prevention. In Kenya, Nigeria and Senegal, discriminatory laws targeting MSM and lesbians still exist, according to IGLHRC. "If anything is increasing the vulnerability of gay men in Africa with HIV," a representative of the IGLHRC said, "it is sodomy laws that prevent people from speaking honestly about who they are and that push people further away from HIV prevention services." Click Here
System Started in Rwanda Suggests That Use of Cell Phones May Improve HIV Care
A clever medical reporting and tracking system that relies on cell phones may enable the provision of better health care to HIV-infected individuals in resource-limited areas, the New York Times reports. Launched two years ago in Rwanda to track individuals living with HIV, the system has since been expanded to allow health care workers in the field to send reports via cell phone directly to a central database. The system is said to connect 75% of Rwanda’s 340 clinics, which covers 32,000 people. The technology enables health care workers to track infected individuals, continuously monitor stocks of antiretroviral drugs and generate monthly reports on the number of HIV-infected individuals with access to antiretrovirals. Voxiva, the maker of the cell phone system, has recently entered into a public-private partnership to launch a new $10-million campaign that will use cell phones to bolster HIV care and treatment in 10 African countries. Currently, 60% of Africans live in areas with cell phone coverage; this figure is projected to increase to 85% by 2010. Click Here |
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