Abstract
Avoid Nevirapine After Childbirth
Although nevirapine should be used to prevent mother-to-child HIV transmission, it may not be wise to include it as part of an antiretroviral drug regimen after childbirth in women who have taken it during pregnancy. In a new study, researchers at the University of Alabama at Birmingham (UAB) have found that such women should not use nevirapine for at least 1 year after childbirth.
Although nevirapine works well to prevent mother-to-child HIV transmission, a single dose of nevirapine in infected pregnant women can trigger resistance to some antiretroviral regimens. However, after 12 months, the nevirapine-induced resistance fades and no longer affects the efficacy of the regimen.
The UAB study included 878 infected women in Zambia, Cote d'Ivoire, and Thailand. In total, 355 of the women were exposed to nevirapine, whereas 523 had been exposed to nevirapine before enrollment. Some were given single-dose nevirapine, and others were not; all participants were given ART immediately on confirmed infection and monitored for 1 year.
Researchers defined therapy failure as death, discontinuation of the nevirapine-containing regimen, or a viral load of ≥400 copies/mL at either 24 or 48 weeks. Among the 355 women exposed to nevirapine, 114 (32.1%) met the criteria for treatment failure. Of 523 women not exposed to nevirapine, for 132 (25.2%), therapy failed. The researchers stratified the women enrolled by interval categories between exposure and starting antiretroviral therapy. Failure rates (versus those of unexposed women) were highest in women for less than 6 months (47 of 116 women, 40%). An inverse relation was found between virologic failure and exposure interval. Overall, women with prior exposure to single-dose nevirapine during pregnancy had an increased risk of treatment failure after childbirth if they continued taking the drug. Women with a more-recent exposure were most at risk.
According to the researchers, women can safely use standard, first-line therapies in their countries after using nevirapine to prevent mother-to-child transmission, provided they wait 12 months after giving birth. Those women who need treatment sooner should use an antiretroviral regimen that does not contain nevirapine. A good choice of regimen for these women would be one that is PI based.
The study was published in the February 15 online journal PLoS Med, 2010;7(2): e1000233.
San Francisco Benefits from Decreased Community Viral Load
Both improved uptake in the use of combination antiretroviral therapy and increased testing rates have resulted in a decrease in community viral load in San Francisco, California. As a result, the city saw a decrease in the number of new cases of HIV infection between 2004 and 2008.
Researchers from the San Francisco Department of Public Health calculated the total and mean viral load in the city. These calculations were made from data collected by the San Francisco HIV/AIDS surveillance system. The city requires that laboratories report viral loads to the health department. For the study, mean community viral load consisted of the mean of the most recent HIV viral load of all reported HIV-infected persons in San Francisco, divided by the number of reported HIV-positive people in the city. The researchers evaluated the relation between viral-load measures and newly reported HIV infections and the incidence of HIV. They also examined the relation between the annual total and mean viral load with population-based incidence estimates obtained from the Centers for Disease Control and Prevention (CDC).
An association was found between community viral load and the number of new HIV infections. Although the CDC model estimated that the community viral load would predict the incidence of HIV, the researchers did not find this in their study. Greater community viral loads were found for several specific populations living in San Francisco, including African Americans, members of the transgender community, and users of injection drugs. The researchers attribute the overall decreases in community viral load to greater use of antiretroviral therapy during the past 5 years.
The findings were presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI), abstract 33.
Tenofovir/Emtricitabine Combination Results in Lower Bone-Mineral Density
A late-breaker presentation at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) points to bone-density problems with the use of the antiretroviral combination of tenofovir/emtricitabine. Results from the study show that patients treated with this combination had greater and larger declines in bone-mineral density overall, and specifically in the lumbar spine, compared with patients receiving abacavir/lamivudine.
Researchers from Case Western Reserve University in Cleveland, Ohio, monitored 269 patients with HIV for 96 weeks. Patients were randomized to receive one of four different antiretroviral regimens: abacavir/lamivudine or tenofovir/emtricitabine with either ritonavir-boosted atazanavir or efavirenz.
All four treatment groups experienced significant decreases in bone-mineral density. The most significant changes were observed during the first year of therapy. Patients in the atazanavir/ritonavir groups had more losses in lumbar spine bone-mineral density compared with patients receiving efavirenz. However, they did not experience more loss in hip bone-mineral density.
The study was presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI), abstract 106LB.
Arrhythmia Risk with Saquinavir
The Food and Drug Administration (FDA) is currently reviewing clinical trial data about a potentially serious effect on the heart from the use of saquinavir (Invirase®) in combination with ritonavir (Norvir®). The data suggest that together the two drugs may affect the electrical activity of the heart, specifically causing prolonged QT or PR intervals. A prolonged QT interval can increase the risk for abnormal heart rhythms, including torsades de pointes. A prolonged PR interval can cause heart block.
Invirase and Norvir should not be used in patients already taking medications known to cause QT-interval prolongation such as class IA (such as quinidine,) or class III (such as amiodarone) antiarrhythmic drugs; or in patients with a history of QT-interval prolongation. The FDA also recommends that healthcare professionals not use Invirase in patients with a history of QT-interval prolongation, preexisting conduction-system disease, ischemic heart disease, cardiomyopathy, or underlying structural heart disease.
The warning is based on data by Roche based on the FDA request that all manufacturers of protease inhibitors, including Invirase, conduct a thorough QT study to evaluate the effect these drugs have on the QT and PR intervals. Preliminary data show that when Invirase boosted with Norvir (1,000 mg/100 mg) was given to healthy patients, ages 18 to 55 years, a dose-dependent prolongation of the QT and PR intervals occurred. The magnitude of the effect and clinical implications of QT- and PR-interval prolongation are still being reviewed by the FDA.
These findings suggest that some patients using Invirase boosted with Norvir may be at an increased risk for developing abnormal heart rhythms. In particular, this risk may be increased in patients using other medications known to cause QT-interval prolongation such as class IA and class III antiarrhythmic drugs or in patients with a history of QT-interval prolongation.
Patients who appear to develop rhythm disturbances from treatment should be reported by their physicians to the FDA MedWatch program by calling (800) 332–1088.
Treatment with Antiretrovirals Increases Pregnancy Rates
A study conducted in a multicountry HIV-treatment program in sub-Saharan Africa found that pregnancy rates increased in women with HIV infection after they started taking antiretroviral therapy.
Researchers from the University of Cape Town, South Africa, analyzed data from the Mother-to-Child Transmission-Plus initiative (MTCT-Plus). In seven African countries, the MTCT-Plus initiative offers family-centered treatment, including checkups, blood tests, counseling, and ART, when appropriate. The study was designed to determine how treatment with antiretroviral therapy affected pregnancy rates among HIV-infected woman.
Over a 4-year period, the researchers found that nearly a third of the women starting antiretroviral therapy experienced a pregnancy. The chance of pregnancy increased over time in women who had started to receive ART. However, pregnancy rates remained low and constant in women who were not yet receiving ART. As expected, other factors, such as age, lower educational status, and less-reliable forms of contraception also affected pregnancy rates. Although the study cannot explain why women receiving antiretroviral therapy are more likely to become pregnant, the researchers offer behavioral explanations for the findings. For example, women receiving antiretroviral therapy are more likely to feel motivated to have children, as their health improves.
More details about the study can be found in the online journal PLoS Medicine, 2010;7(2): e1000229.
HIV Infection in IVDUs Decreases with Expanded HIV Treatment Coverage
A comprehensive population-based study, conducted by the BC Centre for Excellence in HIV/AIDS, shows that expanded highly active antiretroviral therapy (HAART) coverage was associated with a 50% decrease in new yearly HIV infections among injection-drug users. The increased HAART coverage also resulted in a decrease in the community HIV plasma viral load in British Columbia. These findings follow an earlier study by the Centre showing that 5-year mortality is similar between HIV-infected injection-drug users and nonusers infected with HIV and treated with HAART. Results from this new study show that HAART's secondary benefit of HIV prevention will also be experienced by drug users.
Based on the results from these two studies by the Centre, government officials in British Columbia have announced a new C$48-million, 4-year initiative to enhance HAART outreach to hard-to-reach populations in the province, including injection-drug users. Known as Seek and Treat to Optimize Prevention of HIV and AIDS (STOP HIV & AIDS), the initiative is aimed at curbing the transmission of HIV and decreasing AIDS-related morbidity and mortality. Specific efforts will be made to identify and test individuals at risk (seek), engage them in care, put them on HAART, and use harm-reduction strategies.
The findings were presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI).
Recent FDA Approvals and Changes
Earlier this year, the FDA approved a new tablet formulation of Norvir® (ritonavir). The 100-mg tablets do not require refrigeration.
According to the package insert, unlike the capsule formulation, Norvir tablets must be taken with meals. Patients who take the 600-mg twice daily soft-gel capsule Norvir dose may experience more gastrointestinal side effects, such as nausea, vomiting, abdominal pain, or diarrhea, when switching from the soft-gel capsule to the tablet formulation. This is because a greater maximal plasma concentration (Cmax) is achieved with the tablet formulation relative to the soft-gel capsule. These adverse events (gastrointestinal or paresthesias) may diminish as therapy is continued. Norvir tablets are not bioequivalent to NORVIR capsules. Under moderate-fat conditions (857 kcal; 31% fat, 13% protein, 56% carbohydrates), when a single 100-mg Norvir dose was administered as a tablet compared with a capsule, the AUC(0-∞) met equivalence criteria, but the mean Cmax was increased by 26%.
Also earlier this year, the FDA granted tentative approval for efavirenz cross-scored tablets, 200 mg, manufactured by Strides Arcolab Limited of Bangalore, India. The cross-scored tablet can be broken into two 100-mg or four 50-mg doses to facilitate pediatric dosing.
The Intelence™ (etravirine) label has been updated and revised by the FDA to include new drug–drug interaction information between etravirine and fluconazole, voriconazole, lopinavir/ritonavir tablets, and clopidogrel. Co-administration of etravirine and fluconazole or voriconazole significantly increased etravirine exposures. The amount of safety data for these increased etravirine exposures is limited; therefore, etravirine and fluconazole or voriconazole should be co-administered with caution. No dose adjustments of Intelence, fluconazole, or voriconazole are needed. Intelence and Kaletra (lopinavir/ritonavir) tablets can be co-administered without dose adjustment. The activation of clopidogrel to its active metabolite may be decreased when clopidogrel is co-administered with Intelence. Alternatives to clopidogrel should be considered.