Abstract
HIV AND AIDS
Fewer HIV Drugs in Development
The available selection and success of current antiretroviral agents targeting HIV infection, while making it possible for infected individuals to live longer, healthier lives, has also had a negative effect on the HIV drug development pipeline. With far fewer HIV drugs in development at present compared to even 5 years ago (60 versus 100 in 2006), patients may be at risk if the virus mutates and becomes resistant to currently available drug cocktails. Even as the number of infected people continues to increase globally—including approximately 56,000 new cases in the United States each year, and more than 33 million people with living with HIV in 2009, only 6 of the 31 AIDS drugs on the market were approved since 2004. The last new AIDS drug gained approval 3 years ago.
Several factors are driving the decline in AIDS drug development, with most a result of the challenges companies face in besting what is currently available and overcoming the economic hurdles to do so. For example, the FDA now demands longer clinical studies and more data, and physicians will need strong evidence of improved efficacy and safety before putting their patients on a new drug or replacing a drug in an existing regimen. The efficacy and relative safety of current drug cocktails that provide a multipronged attack on the AIDS virus have set the bar high for new drug discovery efforts. Furthermore, most HIV patients who would be suitable subjects for a clinical trial of a new agent are already on an effective treatment regimen, making it more challenging to demonstrate a significant clinical effect compared to testing in treatment-naïve patients.
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HIV-Infected Persons More Susceptible to Bone Fractures
Results of the HIV Outpatient Study (HOPS) indicate that among the nearly 6000 HIV-infected persons followed during the study period 2000–2008, the age-adjusted rate of first bone fractures at any anatomic site was higher than the rates for the general U.S. population. Risk factors for fracture in the HOPS group included older age, substance abuse, nadir CD4+ cell count less than 200 cells/mm3, hepatitis C infection, and diabetes. The authors note that low bone mineral density is common among persons with HIV infection and recommend regular assessments for fracture risk.
Source: Young et al. Clin Infect Dis 2011. doi: 10.1093/cid/ciq242.
HIV Therapy Managed by Nurses is Effective and Cost Efficient in a Resource-Poor Setting
A pilot program in South Africa in which HIV patients on a stable antiretroviral regimen were treated by nurses at regional clinics—called “down-referral clinics” were more likely to be in treatment and responding a year later compared to patients cared for by physicians at larger hospitals, according to unpublished findings reported at the Conference on Retroviruses and Opportunistic Infections, held February 27 to March 2, 2011, in Boston, Massachusetts. After a year, 98% of the patients assigned to a nurse-managed clinic were still coming for treatment, compared to 93% of the patients receiving therapy at the central hospital. Additionally, the study conducted by health care professionals at Boston University's School of Public Health, found that treatment costs for the nurse-managed care were approximately 10% lower, translating to a $48 savings per patient over the course of the study. They suggest that broader use of this care model in down-referral clinics throughout South Africa would have the potential to save $12 to $20 million per year—money that could be used to provide treatment to more patients.
Source: Source: CDC HIV/Hepatitis/STD/TB Prevention News Update.
Five-Drug HIV Cocktail not Better than Standard HAART
Unpublished data presented at the recent Conference on Retroviruses and Opportunistic Infections from the first 48 weeks of a 96-week study comparing the use of a five-drug therapeutic cocktail with a standard three-drug antiretroviral regimen to treat acute and early-stage HIV infection demonstrated no differences in the levels of HIV RNA in the blood or of other immune system measurements. The three-drug arm of the study included the reverse transcriptase inhibitors tenofovir and emtricitabine and a boosted protease inhibitor (atazanavir or darunavir). Patients in the five-drug study arm received these same there drugs as well as the viral entry inhibitor maraviroc and the integrase inhibitor raltegravir. The main difference between the groups was a shorter time to undetectable HIV RNA levels in the blood of patients on the five-drug regimen, but by 24 weeks, there was no significant difference in the proportion of patients in each group with undetectable virus. No significant differences were found in recovery of CD4+ cells, levels of proviral DNA or cell-associated HIV RNA or their rates of decay over time, levels of naïve and total CD4 cells, or levels of immune system activation markers.
Source: CDC HIV/Hepatitis/STD/TB Prevention News Update.
FDA Warning Targets Kaletra Use in Premature Babies
The FDA issues a warning of serious health problems in premature babies given the Abbott drug Kaletra®, an oral solution of lopinavir/ritonavir. Kaletra containes alcohol and propylene glycol, and the diminished ability of premature babies to eliminate propylene glycol could lead to adverse events such as serious heart, kidney, or breathing problems. The FDA warns against use of Kaletra in premature babies until they are at least 14 days past their due date and in full-term babies younger than 14 days of age. If a health care professional believes that the use of Kaletra to treat HIV infection immediately after birth outweighs the potential risks, then the FDA strongly recommends monitoring for increases in serum osmolality, serum creatinine, and other signs of toxicity.
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Condom Use and Risk of HIV Transmission from Homosexual Men in Treatment to Their Uninfected Partners
Condom use at all times offers the best protection against transmission of HIV from an infected homosexual man receiving antiretroviral treatment (ART) to an uninfected partner. When condom use is less than complete, however, and its use is based on the results of viral load measurements, the best strategy is to use condoms when the last undetectable viral load was measured more than 3 months previously, according to a study of men who have sex with men performed in The Netherlands. The study found that without condom use the risk of an HIV-infected man on ART transmitting the virus to an uninfected partner is 22%. With incomplete condom use, defined as use in 30% of sex acts, the risk of HIV transmission declines slightly to 17%. When the decision to use a condom depends on the results of viral load measurements, the risk of transmission drops as low as 3% if men use condoms when their last undetectable viral load result was 6 months or longer ago. The study by Hallett and colleagues demonstrated that the risk of HIV transmission can be reduced even further if men base the decision to use condoms on last-undetectable-viral-load results from no more than 3 months previously.
Source: Sex Transm Infect 2011;87:17–21.
Abacavir Poses No Greater Heart Attack Risk than Other HIV Drugs
In response to conflicting information linking the antiretroviral drug abacavir to an increased risk of heart attack, the FDA conducted a meta-analysis of 26 randomized clinical trial in which abacavir was evaluated and concluded that there is no increased risk of myocardial infarction with use of the drug. The FDA recommends that health care professionals continue to prescribe abacavir according to label instructions and that patients not stop taking abacavir without first talking to their doctor.
HEPATITIS C VIRUS
Interim Results of Telaprevir in HIV/HCV Coinfection Are Promising
Vertex Pharmaceuticals presented interim results from a phase 2 study comparing the addition of telaprevir (an oral hepatitis C virus [HCV] protease inhibitor) to treatment with a combination of pegylated-interferon and ribavirin, versus the two-drug therapy alone in patients with HCV-HIV coinfection, at the recent Conference on Retroviruses and Opportunistic Infections. All of the 60 patients were treatment-naïve for HCV. Interim data were collected at week 4 of treatment and showed that 70% of patients receiving telaprevir-based combination therapy had undetectable HCV compared to 5% of patients receiving only pegylated-interferon and ribavirin, suggesting a rapid antiviral response to telaprevir. Most of the adverse reactions in the telprevir arm were mild or moderate; they included pruritus, nausea, dizziness, pyrexia, anorexia, and vomiting. Vertex is conducting a two-part study of the telaprevir combination therapy: Part A is evaluating the therapy in patients not receiving antiretroviral therapy for HIV infection; and Part B is evaluating the therapy in patients receiving ART comprised of either emtricitabine/tenofovir/efavirenz or a regimen including ritonavir-boosted tazanavir, tenofovir, and emtricitabine or lamivudine.
Source: CDC HIV/Hepatitis/STD/TB Prevention News Update.