Abstract
Renal Function Decline Observed with Tenofovir
Low body weight and body mass index (BMI) appear to be associated with renal function decline in patients taking tenofovir. The findings come from a study of HIV-infected patients in Thailand conducted by researchers from Ramathibodi Hospital in Bangkok.
The researchers conducted both retrospective and prospective cohort studies, enrolling patients who had started treatment with tenofovir. Renal function was defined as a decrease of 25% in glomerular filtration rate (GFR) from baseline. The researchers determined what factors were associated with any decline in renal function. For this study, a total of 405 patients were enrolled. Median body weight was 56.5 kg. All except 4 patients were antiretroviral-experienced. Patients received tenofovir for a median duration of 16 months.
Of 405 patients, 78 (19.3%) experienced a 25% decrease in GFR. This amounted to an incidence rate of 16.2 per 100 person–years. Kaplan-Meier survival analysis determined that the median time to such a decrease in renal function was 28 months. Factors associated with a 25% decrease in GFR included a lower body weight and BMI. Other factors were baseline GFR and if patients were receiving protease inhibitors or mephrotoxic drugs. According to the researchers, physicians should closely monitor patients who have these risk factors when receiving tenofovir therapy.
More details can be found in the October 2010 issue of the journal Current HIV Research 2010;8:504–509.
Study Compares Four Real-Time Viral Load Assays
Since the accurate measurement of viral load is critical to the therapeutic management of HIV, misestimating value can lead to suboptimal treatment and the development of resistance. A group of researchers from France recently compared the results from four commercial real-time assays to measure their reliabilities. They found a variety of differences in estimating viral load and other measurements.
Four commercially available tests were used in this study. These were the Abbott m2000 RealTime HIV-1 (Abbot Laboratories, Abbot Park, IL), the bioMérieux NucliSens Easy QR HIV-1 version 1.2 test) bioMérieux, Marcy l'Etoile, France), and versions 1.0 and 2.0 of the Cobas AmpliPrep/Cpbas TaqMan assays (Roche Diagnostics, Basel, Switzerland). Each of the four tests was performed on blood samples obtained from 74 consecutive patients in a blinded fashion.
The means of difference were null between version 2.0 of the CAP/CTM and the Abbott assay for CRF02_AG subtypes. However, it was positive in favor of CAP/CTM version 2.0 for genotypes B and negative in favor of NucliSens for all genotypes. The researchers found that the standard deviation of difference ranged from 0.3 to 0.59. This depended on the considered couple of assays. In addition, the reliabilities of all four tests, appreciated by the standard deviation of difference between measurement and the estimated “true” viral load and by the coefficient of reliability, were significantly different among each other. Other significant differences were seen within each group of HIV-1 genotype. Such disparity was higher for the CRF02_AG subtype compared to the B subtype. Given the risks of misestimating viral load with different assays, the researchers recommend that physicians use the same assay each time they monitor their patients.
The study was published ahead of print online on November 10, 2010 in the Journal of Clinical Microbiology.
Carotid Intima-Media Thickness Decreases with Atazanavir
Controversy continues over how antiretrovirals affect cardiovascular health in patients with HIV infections. Boosted atazanavir is a protease inhibitor that does not provide major dyslipidemia or insulin resistance. French researchers recently used an observational cohort study to determine the cardiovascular effects of atazanavir. Specifically, their main outcome was the degree of carotid intima-media thickness after therapy with this protease inhibitor. They found that atazanavir significantly decreased this thickness after 18 months.
The researchers enrolled 229 patients with HIV infection. Of these, 33 patients were treated with antiretroviral regimens containing ritonavir-boosted atazanavir. These individuals were compared to 99 age- and gender-matched controls who were not taking boosted atazanavir. Carotid intima-media thickness was measured at baseline and then again at 6-, 12-, and 18-month intervals.
At study entry, there was little difference in carotid intima-media thickness between the two groups. By 18 months, however, there was a significant decrease in carotid intima-media thickness in the 33 patients receiving boosted atazanavir. This difference remains significant even after the researchers adjusted for such factors as high-density lipoprotein (HDL)-cholesterol levels, cardiovascular family history, and exposure to other antiretrovirals including nucleosides.
More details can be found in the November 27, 2010 issue of AIDS 2010;24:2797–2801.
HIV Patients Diagnosed with Lung Cancer at a Younger Age
Patients with HIV are at an increased risk for primary lung cancer. Researchers from Virginia Mason Medical Center in Seattle, Washington, recently studied the characteristics of HIV patients with lung cancer and compared them with other patients with lung cancer who did not have HIV. One of their findings was that HIV patients with lung cancer were diagnosed with their cancer at a younger age compared to patients with lung cancer patients HIV.
A multi-institutional, international collaboration provided the researchers with a database of 75 patients with HIV infection and primary lung cancer. Their characteristics were studied and compared to data from the Surveillance Epidemiology and End Results program (SEER) containing information on 169,091 individuals. Another comparison was made with HIV-infected patients without lung cancer from the Adult and Adolescent Spectrum of HIV-Related Diseases (ASD) project containing 36,569 participants.
For patients with HIV infection and lung cancer, the median age at cancer diagnosis was 50 years. This compares with 68 years of age in the SEER group. HIV-infected cancer patients (77%) were similar to the SEER individuals (70%) in presenting most frequently with stage IIIB/IV cancers. Rates were similar for adenocarcinoma (46% versus 47%) or squamous carcinoma histologies (35% versus 25%). When the researchers compared the group of HIV lung cancer patients with the ASD group, they found similar median nadir CD4+ cell counts. The cancer patients had counts of 138 cells/mm3 while the ASD participants had counts of 160 cells/mm3. At the time of their lung cancer diagnosis, HIV patients had a median CD4+ cell count of 340 cells/mm3; the majority (86%) received antiretroviral therapy. Of the 75 patients with HIV and lung cancer, 63 were receiving treatment for their cancer. However, they experienced significant toxicities from chemotherapy. The median survival was 9 months for HIV patients and SEER participants with stage IIIB/IV lung cancer.
The study was published in the November 1, 2010 Clinical Lung Cancer 2010;11:396–404.
Factors Predict Likelihood of Viral Suppression
Canadian researchers have identified a number of factors that are associated with virologic suppression in HIV patients receiving highly-active antiretroviral therapy (HAART). Identifying patients who are at risk for diminished suppression can help focus efforts on maximizing the benefits of HAART in these individuals.
In this multisite Canadian cohort, 3555 individuals were enrolled. Their median age was 40 years; 80% were male. Eligibility included being HIV positive and antiretroviral-naïve. They started treatment on or after January 1, 2000. All patients had viral load and CD4+ cell counts taken within six months of starting therapy. Virological suppression was considered to be the time to the first of at least two consecutive viral load measurements of less than 50 copies per milliliter.
The median time to suppression was 4.55 months. Factors associated with an increased likelihood of suppression included older age, male gender, and not having a history of injection drug use. In the cohort of 3555 individuals, 18% had a history of injecting drugs. Having an AIDS diagnosis at baseline also predicted an increased likelihood of suppression; 13% presented with an AIDS-defining illness at baseline. In addition, suppression was more likely for individuals with low baseline viral loads compared to those with a viral load of 5 log10 copies per milliliter or more. By 18 months of follow-up, this effect of viral load stopped. In terms of specific therapies, non-nucleotide reverse transcriptase inhibitors (NNRTIs) and ritonavir-boosted HAART were associated with the likelihood of suppression.
More details can be found in the online, ahead of print November 8, 2010 edition of HIV Medicine.
Viral Escape in Cerebrospinal Fluid is Common in Patients on Suppressive Therapy
Reports have been published of cases in which there is HIV viral escape into cerebrospinal fluid (CSF) in patients receiving suppressive antiretroviral therapy. A group of international researchers have looked at this phenomenon in 69 patients with HIV and no neurologic symptoms. They have found that viral escape in CSF is actually more common than previously reported. As a result, even well-treated patients with HIV may continue to have low-grade CNS infection.
All of the 69 patients participating in the study were treated with antiretroviral therapy for more than 6 months. In addition, they all had viral suppression defined as having plasma HIV-1 RNA of less than 50 copies per milliliter. Patients were on regimens consisting of efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. The researchers measured HIV-1 RNA and neopterin levels.
Only 7 of the 69 participants (10%) had detectable HIV-1 RNA levels in their CSF. The median level was 121 copies per milliliter. Those individuals with detectable HIV in their CSF were found to have significantly higher levels of neopterin in their CSF. They also had longer durations of treatment. The subjects with CSF escape were more likely to have previous treatment interruptions. According to the researchers, the effectiveness rank of central nervous system penetration was not found to be a predictor of detectable virus or neopterin levels in the CSF.
The study was published in the online, ahead of print, November 4, 2010 edition of Journal of Infectious Diseases.
Case Report Shows Interaction between Enfuvirtide and Niacin
Researchers from the University of Texas Health Science Center in San Antonio have recently reported on a case involving a drug–drug interaction between enfuvirtide and niacin. The 47-year-old male patient suffered from dilated cardiomyopathy and prolonged QT syndrome. He had an automatic implantable cardiovascular defibrillator device.
For his HIV infection, the patient was taking subcutaneous enfuvirtide 90 mg twice daily as part of his antiretroviral regimen. He was also taking 500 mg/d of oral extended-release niacin to improve a HDL-cholesterol level of 8 mg/dL. Following 1 week on both medications, the patient started to have extreme redness, edema, and swelling at the enfuvirtide injection site. This also corresponded with the patient experiencing a flushing sensation from the niacin. Both reactions interfered with his daily activities. As a result, the patient elected to discontinue both therapies. Prior to receiving the niacin, the patient had tolerated the enfuvirtide. The patient's doctor restarted enfuvirtide and closely followed the patient. According to the researchers, the patient continues to take enfuvirtide without any further consequences.
The researchers believe that there was a drug–drug interaction between the enfuvirtide and the niacin. They hypothesize that this interaction is a result of prostaglandin synthesis and the mobilization of inflammatory cells, particularly Langerhans cells. According to their hypothesis, the Langerhans cells in the epidermis function improperly as a result of the presence of HIV and the attachment of enfuvirtide. Once the cells are exposed to nicotinic acid, they produce an exaggerated immune response. This response is characterized by pain, redness, and swelling at the enfuvirtide injection site. In addition, other inflammatory molecules, including prostaglandins and cytokines, may also have roles in this drug–drug interaction.
More details about this case report can be found in the November 2, 2010 online ahead of print edition of the Annals of Pharmacotherapy.