Abstract
Antiretroviral Approaches Both Effective in Preventing HIV Transmission from Breast Milk
The largest study to date examining methods to prevent HIV infection among breastfeeding infants concludes that both giving antiretroviral drugs to HIV-infected breastfeeding mothers in sub-Saharan Africa and giving an HIV-fighting syrup to their babies are effective. However, researchers from the UNC School of Medicine believe that the infant regimen is the more effective of the two. In addition, the maternal regimen is considerably more expensive and requires health-care access not always found in developing countries. Each year, approximately 200,000 infants worldwide become infected with HIV through breastfeeding. Throughout the developing world, infant formula is both prohibitively expensive and associated with increased infant deaths.
In the study, called the Breastfeeding, Antiretrovirals, and Nutrition Study (BAN), 2,369 breastfeeding mother-infant pairs in Lilongwe, Malawi, were randomly assigned to one of three groups. The first was a maternal antiretroviral therapy (ART) group. In the second group, infants were treated with nevirapine liquid. Finally, a control group had medications given at the time of delivery only. In none of these women has AIDS developed yet, and so they did not need treatment.
After their babies were born, women in the maternal antiretroviral group received a single tablet twice a day containing the drugs zidovudine and lamivudine. They also received a dose of nevirapine by mouth once a day for 14 days and then twice daily from 2 to 28 weeks.
In the infant prophylaxis group, each infant received a dose of liquid nevirapine by mouth that increased with age, ranging from 1 ml per day in the first two weeks to 3 ml per day for weeks 19 through 28. Study personnel measured these doses into syringes. These were then given to the mothers, who then squirted the contents into their infants' mouths.
Mothers in the study were asked to wean their babies from breastfeeding by 28 weeks after birth. The study results were calculated after each participant in the treatment arms had completed 28 weeks of treatment. Results showed that infant nevirapine was 74% effective in preventing HIV transmission, whereas maternal antiretroviral therapy was 53% effective. In addition, the study found that infants had significantly increased HIV-free survival no matter which intervention was used.
Based in part on these results, the World Health Organization (WHO) has recommended that HIV-prevention guidelines for breastfeeding HIV-infected mothers who are still in the early stages of HIV infection be modified to offer them the choice of either dosing their uninfected infant with nevirapine syrup during breastfeeding or taking a triple-drug regimen themselves.
The study was published in the June 17 issue of the New England Journal of Medicine, 2010;362:2271–2281.
Nucleic Acid Testing Increases HIV Detection Yield
Community-based HIV testing programs generally use only HIV antibody testing, but nucleic acid testing (NAT) can detect the presence of HIV earlier. Researchers at the University of California, San Diego, School of Medicine studied more than 3,000 patients who sought HIV testing in community-based clinics in or near San Diego to examine the yield of testing with a rapid test plus NAT and to see whether patients would be willing to access their results by phone or computer. The findings showed that NAT testing increased the HIV-detection yield by 23%. In addition, a large majority of study participants received their negative test results by automated phone or Internet systems. Such automatic systems may increase case yields in programs that are geared to men having sex with men (MSM).
The patients were first tested for HIV with a rapid saliva test. If the result was positive, a counselor informed the patient, and blood was obtained for a standard HIV test. If the result was negative, blood was obtained for an NAT. Nearly one fourth of persons with identified cases of HIV had positive results only by NAT testing. More than two thirds of patients with negative NAT results retrieved them with computer or voicemail.
Most participants in the San Diego study (56%) and those with HIV (91%) were men having sex with men. According to the researchers, those with higher incomes, younger ages, no testing at substance-abuse rehabilitation centers, no recent syphilis, and no methamphetamine use were more likely to access negative NAT results with either Internet or voicemail systems.
The study was published in the June 15 issue of the Annals of Internal Medicine, 2010;152:778–785.
Directly Observed HIV Therapy by Patient-Selected Supporter Improves Survival
When applied to HIV care, the community-based model of directly observed therapy (DOT) has no effect on virologic outcomes. However, providing such support does significantly improve patient survival. The finding comes from a recent study conducted by researchers at Johns Hopkins Bloomberg School of Public Health, in collaboration with a team at the University of Cape Town, South Africa. They conducted the first randomized controlled trial of patient-nominated treatment supporters providing partial DOT in resource-limited settings. Mortality rates were lower among DOT patients than among those using self-monitored antiretroviral therapy (ART).
For the study, researchers analyzed data from 274 adult patients initiating ART at a public HIV clinic in Cape Town, South Africa. Patients were randomized to treatment-supporter DOT-ART or self-administered ART. In the DOT group, patients selected someone from their own personal network such as a family member or friend, to observe at least one medication dose every day and to provide support. DOT-ART patients and supporters received baseline and follow-up training and monitoring. Researchers defined the primary end points as the number of patients with undetectable HIV viral loads (<400 copies/ml) and a mean change in CD4 cell counts at 6, 18, 12, and 24 months. Secondary end points were pill-count adherence, new or recurrent AIDS-defining illness, and all-cause mortality.
The proportion of patients who had viral loads of < 400/copies/ml at 12 months were 72.8% in the DOT-ART arm and 68.4% in the Self-ART arm. Those patients participating in the DOT-ART arm had greater median CD4 cell-count increases at 6 months (148 cells/mm3). However, all other time points demonstrated similar results. Survival was found to be better in the DOT-ARM, with nine deaths (6.6%) occurring. This is compared with 20 deaths (14.6%) in the Self-ART arm. Mortality was found to be independently associated with study arm.
The study was published in the June 1 issue of AIDS, 2010;24:1273–280.
Crystal Structure of Tat Protein Created
Researchers at the University of Iowa Carver College of Medicine and the University of Nebraska Medical Center (UNMC) have created a three-dimensional picture of the HIV protein Tat. This is the first crystal structure of the HIV protein called Tat, showing it attached to the human protein (P-TEFb) that HIV hijacks during infection. It is hoped that this picture may one day help design better antiretroviral agents. The structure is the result of combining the disciplines of protein chemistry and x-ray crystallography. It shows how Tat latches onto this particular human protein and how the interaction alters the shape of the human protein. This may pave the way for designing inhibitors that target P-TEFb only when it interacts with Tat.
Whereas inhibiting P-TEFb blocks replication of the HIV, P-TEFb is a vital protein in human cells, and inhibiting it kills cells. If an inhibitor could be designed that distinguishes between the P-TEFb attached to Tat and the form that is normal in human cells, that drug might target HIV replication without harming normal cell function. Such compounds could be useful in combination with existing anti-HIV drugs to reduce viral levels further in HIV-infected individuals. In addition, drugs that target P-TEFb may be useful in treating drug-resistant HIV. Targeting a human protein like P-TEFb that the virus needs but cannot mutate may be a successful strategy to counter drug-resistant HIV.
The study was published in the June 10 issue of the journal Nature, 2010;465:747–51.
Tenofovir Improves Dyslipidema
When added to a stable background of antiretroviral therapy, tenofovir improves the lipid profile in patients when compared with a placebo. A double-blind, placebo-controlled crossover study demonstrated that tenofovir improves a variety of lipid parameters significantly. These include non–high-density lipoprotein cholesterol (non-HDL), low-density lipoprotein cholesterol (LDL), and total cholesterol.
Researchers from The Cleveland Clinic in Cleveland, Ohio, enrolled 17 patients with HIV infection who were experiencing dyslipidemia. All had already been treated with stable antiretroviral regimens for a minimum of 90 days. In addition, all of the participants had undetectable viral loads of < 400 copies/ml.
For 12 weeks, each participant had either tenofovir or a placebo added to the stable regimen. Both treatment phases were separated by a 4-week washout period. After 12 weeks of treatment with tenofovir, the median non–HDL-cholesterol levels decreased by 32 mg/dl. Total cholesterol decreased by 39 mg/dl. In addition, the LDL cholesterol decreased by 12 mg/dl. The researchers found that tenofovir had no effect on HDL cholesterol or triglyceride levels. After the washout period, triglycerides rebounded in patients initially receiving tenofovir, increasing above baseline. Throughout the entire study, patients maintained their virologic suppression.
The study was published online ahead of print, May 21, in AIDS.
Starting HAART Late Can Lead to Mother-to-Child Transmission
Starting highly active antiretroviral therapy (HAART) late in HIV-infected women is associated with an increased risk of mother-to-child transmission of HIV. The finding comes from a study of women in Johannesburg, South Africa, by researchers from the David Geffen School of Medicine at UCLA and colleagues in South Africa.
The researchers monitored 1,142 women between January 2004 and August 2008. All were seeking care at antenatal antiretroviral clinics in Johannesburg. Positive infant HIV DNA polymerase chain reaction testing at 4 to 6 weeks predicted mother-to-child transmission of HIV. The women had an average age of 30.2 years.
For the 85% of women who started antiretroviral treatment during pregnancy, the mean HAART duration was 10.7 weeks. It was 93.4 weeks for those women who became pregnant with HAART. Forty-three of 874 women experienced mother-to-child transmission, for an overall rate of 4.9%. No differences were detected between the various HAART regimens used. The rate of mother-to-child transmission was lower in women who became pregnant while taking HAART (0.7%) compared with those starting HAART during pregnancy (5.7%). The researchers discovered that each additional week of treatment in women initiating HAART during pregnancy decreased the odds of transmission by 8%.
The study was published in the Journal of Acquired Immune Deficiency Syndromes, 2010;54:35–41.
Physicians Not Correctly Identifying Drug Interactions
A 4-week audit of an adult ambulatory HIV clinic found that more than one fourth (27%) of patients receiving antiretrovirals were at risk of having a clinically significant drug interaction. Perhaps more alarming is that fact that treating physicians are not adept at correctly identifying these interactions when they occur.
Pharmacologist David W. Kubiak from Brigham and Women's Hospital in Boston, MA, conducted the study to see how widespread is the problem of drug interactions in these patients. During the study, treating physicians recorded all medications being used by patients. These included prescribed medications, as well as over-the-counter products and herbal supplements. The physicians were then asked to identify all of the potential drug interactions that could be deemed clinically significant in the patient. This was defined as being an interaction that could cause excess toxicity or the loss of a therapeutic effect. The researchers then assessed each patient's medication profile for possible drug interactions. This was accomplished by using the Liverpool HIV Drug Interactions website (
In total, 154 patients participated in the analysis. Of these, 86 were receiving a NNRTI; 54, a PI; and eight were receiving both. The researchers were able to identify a total of 213 potential drug interactions. Among these, 86 were considered clinically significant. These 86 drug interactions occurred in 43 patients (27%) and were most common in patients receiving PIs. When the researchers examined how well the treating physicians did, only 31 of these 86 interactions (36%) were correctly identified.
The study was published online ahead of print, June 16 in AIDS Clinical Care.