For the latest updated treatment guidelines for adults and adolescents, children, and pregnant women; postexposure prophylaxis guidelines for occupational and non-occupational HIV exposure; and opportunistic illness (OI) prevention guidelines, visit www.hivatis.org.

ICAAC Conference Highlights

The 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) took place December 16-19, 2001, in Chicago, following a two-month delay due to the events of September 11.

Although no major breakthroughs were announced, several presentations looked at refinements to antiretroviral therapy that aim to make treatment more simple and effective with fewer side effects.

The issue of when to start antiretroviral therapy has been an ongoing controversy. Mattias Egger, MD, from the University of Bristol in the UK presented data from a 13-cohort population comprised of over 12,500 people in the U.S. and Europe. He found that baseline CD4 cell count was the strongest predictor of HIV disease progression or death. There was little difference between people who started therapy with CD4 cell counts of 200-350 cells/mm³ compared with those who started at 350-500 cells/mm³, but the risk of progression was higher in those who started treatment with CD4 cell counts below 200 cells/mm³. Dr. Egger's findings support the recent change in U.S. federal treatment guidelines recommending that anti-HIV therapy start at CD4 cell counts below 350 cells/mm³ rather than below 500 cells/mm³.

In his presentation, Patrick Yeni, MD, of the Hôpital Bichat-Claude Bernard in Paris suggested that a strong recommendation for treatment should perhaps be limited to people with CD4 cell counts below 200 cells/mm³. But Brian Gazzard, MD, of Chelsea and Westminster Hospital in London argued that waiting until CD4 cell counts fall to 200 cells/mm³ may be too late, given that people who have ever had such a low count remain at increased risk for opportunistic illnesses (OIs) such as lymphoma. A. Moreno and colleagues from Ramón y Cajal Hospital in Madrid, Spain, also found that immunological recovery was impaired in people whose CD4 cell counts had fallen below 200 cells/mm³ before they started treatment.

Researchers from GlaxoSmithKline presented results of an analysis suggesting that the treatment delay recommended by the revised guidelines (which were based largely on data from men) could lead to increased disease progression and death in HIV positive women. The researchers reported that based on baseline CD4 cell counts and viral load levels, 59% of women were eligible for treatment under the revised guidelines, compared with 81% under the previous guidelines; they calculated that earlier treatment (as per the old guidelines) could potentially confer a 32% greater survival advantage than delayed treatment.

As an illustration of just how controversial the issue of treatment initiation remains, an audience poll at ICAAC revealed that 47% would recommend treatment for an HIV positive man with a CD4 cell count of 410 cells/mm³ and a viral load of 98,000 copies/mL, while 53% would recommend delaying therapy.

Which drugs to use also remains unresolved. Charles Boucher, MD, PhD, and colleagues from the University of Utrecht in the Netherlands compared people taking a protease inhibitor (PI) regimen, those using a non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and those who alternated between the two types of regimen every three months (the SWATCH study). Using an intent-to-treat analysis (in which all participants are analyzed on the basis of the treatment to which they were originally assigned), 69% of those who alternated between nelfinavir (Viracept, a PI) and efavirenz (Sustiva, an NNRTI) achieved viral loads below 400 copies/mL compared with 57% of those who consistently took either nelfinavir or efavirenz. However, there were no significant differences in toxicities-including lipodystrophy (abnormal body fat redistribution) and blood lipid (fat) abnormalities-which are often cited as a reason for switching to a protease-sparing regimen. In contrast, a study by Christine Katlama, MD, of the Hôpital Pitié- Salpêtrière in Paris and colleagues (the TRIZAL study) did show a decrease in cholesterol and triglyceride levels in people who switched from a PI-based regimen to a Trizivir (AZT/3TC/abacavir) regimen containing only nucleoside reverse transcriptase inhibitors (NRTIs); however, viral rebound was more likely in the Trizivir group.

New information was presented on strategic treatment interruption (STI) and drug cycling, which have become hot new topics in antiretroviral therapy. Joel Gallant, MD, of Johns Hopkins University in Baltimore, Maryland, presented an analysis of 62 people who stopped antiretroviral treatment, in some cases because therapy was no longer indicated under the revised federal guidelines. After a mean follow-up period of 64 weeks, about 75% remained off therapy and were doing well. Of the 25% who resumed treatment (after a mean of 33 weeks), most again achieved a successful virological response.

Several presentations focused on new drugs. Kathleen Squires, MD, from the University of Southern California (USC) in Los Angeles presented an overview of studies of tenofovir DF (Viread), a recently approved nucleotide reverse transcriptase inhibitor. The drug works well in treatment-experienced persons who have developed resistance to other drugs, and is associated with few side effects. Atazanavir is a new PI that can be taken once daily and appears active against certain PI-resistant strains of HIV; it also appears less likely to cause high blood fat levels, although it has been associated with high bilirubin levels (often a sign of liver toxicity). In one presentation, atazanavir regimens (400 or 600 mg/day) were superior to a nelfinavir regimen in reducing viral load. Those taking atazanavir experienced a mean 5% increase in both cholesterol and triglyceride levels, compared with a mean 25% increase in cholesterol and a mean 45% increase in triglycerides among those taking nelfinavir.

A study of tipranavir-the first nonpeptide PI-showed that people experiencing treatment failure who switched to a regimen of tipranavir/ritonavir plus two new NRTIs had a higher response rate than those who switched to saquinavir/ritonavir plus two new NRTIs. (Tipranavir and saquinavir [Fortovase] are given with a small amount of ritonavir [Norvir] to maintain high drug levels in the blood.) Tipranavir appears to be effective against HIV strains that are resistant to older PIs. Further down the pipeline, TMC 114 (an experimental PI) and TMC 125 (an experimental NNRTI) both appear highly potent in early tests. The HIV entry inhibitor T-1249 looks to be more potent than T-20, an earlier drug in the same class; T-1249 can be injected once daily rather than twice daily for T-20.

On the side effects front, several studies presented at ICAAC appear to point to PIs as a major culprit in lipodystrophy and related metabolic disorders, although the ill-defined syndrome is sometimes also seen in people with HIV who are not taking these drugs. Azucena Rodriguez-Guardado from the Hospital Central de Asturias in Oviedo, Spain, presented an analysis of various risk factors in addition to PI use that influence the development of high blood fat levels; these include family history of cardiovascular disease, a high viral load, and ever having a CD4 cell count below 50 cells/mm³. Another study indicated that people coinfected with HIV and hepatitis C virus (HCV) were more likely to experience lipodystrophy than those with HIV alone. Various studies examined the mechanisms by which antiretroviral drugs might cause lipid abnormalities and the effectiveness of various medications in managing high blood fat levels and insulin resistance. Other research examined the role PIs may play in causing bone abnormalities.

Other ICAAC presentations on drug-resistant HIV, genetic variations and treatment success, antiretroviral drugs and birth defects, and heart disease in people with HIV are discussed below. For complete online conference coverage, visit:
www.hivandhepatitis.com/2001conf/icaac2001/main.html, www.medscape.com/viewprogram/507, and www.natap.org/ 2001/ICAAC/ndxICAAC.htm.

XIV International AIDS Conference

The XIV International AIDS Conference will take place July 7-12 in Barcelona, Spain. International AIDS conferences, sponsored by the International AIDS Society, are now held every two years; the last took place in Durban, South Africa, in July 2000. According to an article by Michael McCarthy in the January 5, 2002 issue of The Lancet, this year's conference will be restructured to have a stronger emphasis on prevention, implementation, and policy. Under the new "Barcelona framework," the conference will have two primary components: science and action. There still will be tracks devoted to basic science, clinical research, and public health, but new tracks will be added that focus on prevention, interventions and program implementation, and advocacy and policy. McCarthy noted that conference organizers hope to bridge what they see as "a serious gap between AIDS scientists and people working on the ground in the fight against the worldwide HIV epidemic." The meeting is expected to draw over 15,000 researchers, physicians, policy-makers, activists, and journalists from around the world. Some scholarship funding is available for people with HIV and those working in the HIV/AIDS field. More information about the conference can be found at www.aids2002.com.

FDA Approves One-Pill-a-Day Efavirenz

On February 1 the Food and Drug Administration (FDA) approved a new 600 mg efavirenz pill to be taken once daily. Previously, three 200 mg pills were taken together once per day; 50, 100, and 200 mg pills will remain available. It is recommended that efavirenz be taken on an empty stomach, preferably at bedtime. Efavirenz (sold as Sustiva in the U.S. and as Stocrin elsewhere) must be used as part of a combination regimen with PI or NRTI drugs. The efavirenz package insert also was updated with information about drug interactions with cetirizine (Zyrtec), lorazepam (Ativan), rifabutin (Mycobutin), methadone, and St. John's wort. Bristol-Myers Squibb, the drug's manufacturer, said it hoped the lower pill burden would be easier to take and would help improve adherence.

New Amprenavir/Ritonavir Dosing Regimen

On February 5 the FDA approved a revised dosing regimen for amprenavir (Agenerase) plus ritonavir. The new recommended doses when the drugs are used together are 1,200 mg amprenavir plus 200 mg ritonavir once daily, or 600 mg amprenavir plus 100 mg ritonavir twice daily. Ritonavir increases blood levels of amprenavir because it is metabolized by the same liver enzyme system.

Treatment Delay Safe for Some People

Two studies published in the November 28, 2001 issue of the Journal of the American Medical Association (JAMA) indicate that some people can safely delay starting antiretroviral therapy longer than previously thought. The studies suggest that treatment still can be effective in people who start therapy with CD4 cell counts as low as 200 cells/mm³, even if they have high viral loads.

Robert Hogg, PhD, and colleagues from the University of British Columbia in Vancouver looked at over 1,200 people who started three-drug regimens between 1996 and 1999. Eighty-two had died of AIDS-related causes by 2000. Most of those who died had CD4 cell counts below 200 cells/mm³-and in many cases below 50 cells/mm³-when they started therapy. Yet those who began treatment with CD4 cell counts around 200 cells/mm³ had a survival rate similar to that of people with higher counts at the start of therapy.

Andrew Phillips, PhD, of the Royal Free and University College Medical School in London and colleagues analyzed data from over 3,000 HIV positive people in Europe who began antiretroviral therapy between 1996 and 2000. Those who initiated treatment with CD4 cell counts of 200-349 cells/mm³ did as well as those who started with 350 cells/mm³ or more. Although viral suppression took longer in those with viral loads above 100,000 copies/mL, by 32 weeks they were as likely as those with lower initial viral loads to achieve undetectable HIV RNA levels.

The studies provide further support for the updated U.S. federal guidelines that recommend treatment for people whose CD4 cell counts have fallen below 350 cells/mm³ rather than below 500 cells/mm³. In an editorial in the same issue of JAMA, Roger Pomerantz, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania, said it seemed "prudent" to postpone treatment for some people until their CD4 cell counts approach 200 cells/mm³. However, he cautioned that women with HIV may experience disease progression at CD4 cell levels that do not present a risk for most men, and suggested that people who have recently seroconverted should begin antiretroviral therapy immediately in the hopes of preserving CD4 cell function.

Seven-Day Drug Cycling Effective in Small Study

Mark Dybul, MD, and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID) reported results of a pilot study showing that a small group of people with HIV had successfully used a seven days on/seven days off structured intermittent therapy (SIT) regimen. The research was published in the December 18, 2001 issue of the Proceedings of the National Academy of Sciences. Ten participants with high CD4 cell counts (at least 300 cells/mm³) and low viral loads (below 50 copies/mL), all previously on standard antiretroviral therapy, were selected to stop treatment every other seven-day period for 32 to 68 weeks. During on-treatment weeks, all received a four-drug regimen consisting of d4T (Zerit), 3TC (Epivir), indinavir (Crixivan), and ritonavir. HIV viral load remained suppressed and CD4 cell counts remained at prestudy levels in all who adhered to the cycling regimen. (Two people were dropped from the study because they failed to take their drugs according to schedule.) In this small study, side effects were reduced in the SIT group; in particular, cholesterol and triglyceride levels decreased by 22% and 51%, respectively. In addition to reducing adverse events, such a regimen could reduce the cost of therapy by half, potentially allowing more people in developing countries to receive therapy. However, to date most researchers remain cautious about SIT, noting that much larger studies are needed to determine whether drug cycling will be feasible on a larger scale. People with HIV should not adjust their treatment regimens on their own without consulting their physicians.

Seven-Day Drug Cycling Effective in Small Study

A small study published in the November 24, 2001 issue of The Lancet suggests that treatment response during the first week of antiretroviral therapy may be a good predictor of long-term response. Michael Polis, MD, of NIAID and colleagues looked at the treatment histories of 124 people with HIV (90 children and 34 adults) who had taken part in three different studies between 1995 and 2000. Blood was drawn and analyzed daily for three months. Ninety-five percent of participants who had lower rates of decline in HIV viral load during the first six days of treatment continued to have poorer responses over a longer period, while those with higher rates of viral load decline continued to have better long-term responses. Current guidelines recommend that physicians consider changing therapy if a person has not achieved a good virological response after four weeks or eight weeks of treatment. The new research suggests that physicians perhaps should monitor virological response during the first week of therapy.

Incomplete HIV Suppression Still Has Benefits

Researchers reported in the February 1, 2002 issue of the Journal of Infectious Diseases that people can derive benefits from combination antiretroviral therapy even if their viral loads do not fall to undetectable levels. Steven Deeks, MD, of the University of California at San Francisco (UCSF) and colleagues compared CD4 cell activation and turnover in 36 HIV positive people who experienced virological failure (viral load did not become undetectable while taking antiretroviral therapy), 18 who experienced virological success (viral load did become undetectable with therapy), and 17 who did not receive treatment. The researchers found that CD4 cell activation was greater in the untreated and virological failure groups (13% and 8%, respectively) compared with the virological success group (3%). However, CD4 cell turnover in the virological failure and virological success groups did not differ significantly, and was lower in both groups than in the untreated group. Median CD4 cell half-life was 82 days in the virological success group, 68 days in the virological failure group, and 22 days in the untreated group. The researchers hypothesized that antiretroviral therapy may reduce the virulence of HIV even if it does not suppress the virus completely. They concluded, "Our data indicate that failure of antiretroviral therapy to durably suppress plasma viremia to undetectable levels results in the emergence of a virus population with reduced replicative capacity in vitro, decreased levels of viral replication, and prolonged CD4 T cell survival, compared with findings in untreated HIV-1 infection."

Garlic Lowers Saquinavir Level

According to a study published in the January 15, 2002 online edition of Clinical Infectious Diseases, garlic supplements can interact with saquinavir. Stephen Piscitelli, PharmD, of the National Institutes of Health (NIH) Clinical Pharmacokinetics Research Laboratory and colleagues found that saquinavir levels were decreased in nine HIV negative volunteers after they started taking garlic capsules twice daily. After taking garlic supplements for three weeks, blood levels of saquinavir were reduced by an average of 51%. Ten days after participants stopped taking garlic supplements, their blood levels of saquinavir remained an average of 35% lower than before they took the supplements. Garlic and saquinavir are metabolized by the same CP450 enzyme system in the liver. Judith Falloon, MD, of NIAID recommended that people taking saquinavir should be cautious about using garlic supplements. The researchers did not make a recommendation regarding the use of normal amounts of garlic in the diet as a flavoring agent.

Increased Prevalence of Drug-Resistant HIV

In a late-breaker session at ICAAC, Douglas Richman, MD, of the University of California at San Diego (UCSD) presented results from the first nationwide study of drug resistance. The analysis included 1,080 blood samples from people in the HIV Cost and Service Utilization Study, which includes over 200,000 people with HIV receiving care at various sites in the U.S. since 1996. Samples were tested using the ViroLogic Phenosense assay, a phenotyping test. Researchers found that more than three-quarters of people with detectable HIV viral loads harbored viral strains that were resistant to one or more antiretroviral drugs. When also including people with undetectable viral loads in the analysis, about half had resistant HIV. Seventy percent had NRTI-resistant strains, 42% had PI-resistant strains, and 31% had NNRTI-resistant strains. Over half had HIV that was resistant to two classes of drugs, and 14% showed resistance to all three classes. Some degree of resistance was seen in 87% of those currently on treatment, 41% of those currently not undergoing treatment, and 20% of those who had never received therapy.

Factors associated with resistance included lower nadir (lowest ever) CD4 cell counts (but not lower current counts), higher baseline HIV viral loads, white ethnicity, higher education, and HIV acquisition through male/male sexual activity. People treated at larger medical centers that have more experience treating HIV disease tended to have a lower rate of drug resistance. The higher resistance rates in well-educated, white gay men who have had access to the newest drugs suggest that frequent changes in drug regimens may promote the development of resistance; also, many of these men may have been among the first to receive treatment early in the epidemic when monotherapy was common. Although the implications of the research (which looked at resistance mutations, not loss of virological control) are unclear, Dr. Richman concluded, "We have to use drugs more intelligently."

Gene Variation May Predict Treatment Success

A variation in a gene known as MDR1 that controls a metabolic protein appears to have an effect on how well people respond to antiretroviral therapy, according to a study by Amalio Telenti, MD, of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and colleagues. The MDR1 gene controls production of P-glycoprotein, which has been shown to act as a barrier to drug absorption in certain parts of the body by pumping drugs and other toxins out of cells; in previous studies, the MDR1 gene has been associated with poor response to cancer chemotherapy. There are three genetic variants of MDR1: CC, CT, and TT. People with the TT genotype produce less P-glycoprotein.

Dr. Telenti and his team analyzed levels of efavirenz and nelfinavir in the blood of 123 people with HIV. People with the MDR1 TT variation had higher blood drug concentrations compared with those who had the other two genotypes; those with the CT variation had higher drug concentrations than those with the CC genotype. In addition, those who carried the TT genotype experienced more rapid immune system recovery (as shown by greater increases in CD4 cell counts) after starting antiretroviral therapy compared with those with the CT or CC genotypes. Among whites, 25% have the TT genotype; 50% and 25%, respectively, carry the CT and CC variations. Among blacks, in contrast, an estimated 67-83% carry the CC genotype and the TT variation is seldom seen. This may help explain why some studies have shown antiretroviral treatment to be less effective in blacks.

Dr. Telenti suggested that drugs that inhibit P-glycoprotein could potentially improve response to antiretroviral drugs in people with the MDR1 CT or CC genotypes. The study of genetic differences in drug metabolism is known as pharmacogenomics or pharmacogenetics. Dr. Telenti presented his research at the December ICAAC in what Renslow Sherer, MD, writing for HIVandHepatis.com, called "the one potentially ground-breaking presentation of the conference"; the study was published in the January 5, 2002 issue of The Lancet.

HIV Needs Cholesterol to Infect Cells

Eric Freed, PhD, and Akiro Ono, PhD, from NIAID's Laboratory of Molecular Biology published results in the November 20, 2001 issue of the Proceedings of the National Academy of Sciences showing that HIV requires cholesterol to infect cells. To enter a cell, a viral protein known as Gag must attach to cholesterol-rich patches called rafts in a host cell's membrane. The researchers discovered that by removing cholesterol from cells, they were nearly able to halt production of new HIV particles. Cholesterol was removed using two compounds, one that removes cholesterol from cell membranes and another that inhibits cholesterol synthesis. Said Dr. Freed, "Our research raises the intriguing possibility that widely used cholesterol-lowering drugs might have an effect in humans similar to what we have found in these initial laboratory studies." Cholesterol-lowering drugs already are used by many people with HIV to reduce high blood fat levels associated with the use of antiretroviral therapy.

Heart Disease in People with HIV

Reports continue to accumulate concerning the development of heart disease in people with HIV. A recent Centers for Disease Control and Prevention (CDC) study found a slightly increased heart attack rate among 3,000 HIV positive people using PI-containing regimens compared with the rate among HIV positive people using protease-sparing regimens. But it remains unclear whether the apparent increased risk of heart disease in people with HIV is due to a specific type of antiretroviral therapy, the virus itself, traditional risk factors such as cigarette smoking and obesity, or some other factor(s).

According to research published in the January 1, 2002 issue of Clinical Infectious Diseases, lower nadir CD4 cell counts and longer duration of antiretroviral therapy were associated with ischemic heart disease in people with HIV. Ischemic heart disease is a condition in which the heart muscle is deprived of oxygen due to restricted blood flow through the arteries serving the heart. Max David of the University of Cincinnati College of Medicine in Ohio and colleagues compared data from 16 HIV positive people with cardiovascular (heart and blood vessel) disease and 32 HIV positive people without such disease. In addition to higher rates of traditional cardiovascular risk factors (e.g., cigarette smoking, high blood pressure, elevated cholesterol), the group with cardiovascular disease had a lower mean CD4 cell nadir and longer exposure to NRTI drugs (which may be a marker for longer duration of HIV infection). However, PI exposure was similar in both groups. Carl Fichtenbaum, MD, a member of the research team, suggested that HIV infection may promote the development of atherosclerosis (hardening of the arteries), as do other inflammatory infections such as chlamydia and cytomegalovirus (CMV). In a study of heart disease risk factors presented at ICAAC, Michael Duong, MD, of the Hôpital du Bocage in Dijon, France, and colleagues analyzed coronary artery disease (CAD) risk factors in a group of 99 HIV positive people using combination antiretroviral therapy who had no known history of heart disease. Participants underwent an exercise stress test to detect silent myocardial (heart muscle) ischemia; in a stress test, the subject exercises on a treadmill and electrocardiogram (heart rhythm) and blood pressure tests are conducted. The researchers found no statistically significant differences in type or duration of antiretroviral therapy, length of HIV infection, viral load, or CD4 cell count between those who had positive stress tests (that is, those with evidence of myocardial ischemia) and those with negative tests. Factors associated with myocardial ischemia included obesity, high cholesterol levels, and older age. The authors concluded that a subset of people with HIV are at high risk for heart disease, but mainly due to the same risk factors seen in the general population.

Genital Cancer in Women with HIV

Research published in the January 12, 2001 issue of The Lancet shows that women with HIV are more susceptible to genital and anal cancer than HIV negative women; HIV positive women also are known to be more likely to develop precancerous cervical lesions and invasive cervical cancer. Lois Conley, MPH, of the CDC studied 925 women (481 HIV positive, 437 HIV negative, and seven with indeterminate serostatus) in the New York City area. The women received gynecological exams every six months, including colposcopy (tissue examination using a lighted magnifying instrument) and tests for human papillomavirus (HPV); certain strains of HPV are known to cause genital cancer. At enrollment, 6% of the HIV positive women and 1% of the HIV negative women had genital or anal warts (condylomata acuminata) or lesions. Over the course of the study, HIV positive women were 16 times more likely to develop vulvovaginal or perianal lesions than their HIV negative counterparts; 33 HIV positive women (9%) developed precancerous lesions compared with two HIV negative women (1%).

Women with HIV were also more likely to be infected with HPV (55% of HIV positive women compared with 32% of HIV negative women). After four years of follow-up, HIV positive women with HPV had a 15% chance of developing genital or perianal lesions, including intraepithelial neoplasia (precancerous cell changes); one woman developed invasive anal cancer. The authors recommended regular, thorough examinations (including Pap smears) of the cervix, vulva, vagina, and anus for women with HIV; women with any degree of cellular abnormality should also receive colposcopies and biopsies.

In related news, Howard Minkoff, MD, of Maimonides Medical Center in New York City and colleagues reported in the November 9, 2001 issue of AIDS that treatment with combination antiretroviral regimens appears to improve cervical intraepithelial neoplasia in women with HIV. Among 741 HIV positive women who carried at least one oncogenic (cancer-causing) strain of HPV, those treated with antiretroviral therapy were 40% more likely to experience a regression of cervical lesions and 32% less likely to experience cervical disease progression than women not receiving anti-HIV treatment.

Longer Tuberculosis Treatment for People with HIV

People coinfected with HIV and Mycobacterium tuberculosis are at greater risk for relapse after tuberculosis (TB) treatment and should receive longer treatment regimens, according to researchers from the New York City Department of Health. Cynthia Driver, RN, and colleagues analyzed treatment outcomes in 4,571 people who had received standard four-drug TB treatment (isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin) for at least 24 weeks; none had drug-resistant TB. The rate of TB recurrence (having a positive TB culture less than 30 days after the end of treatment) and relapse (having a positive culture more than 30 days after treatment) was two cases per person-year in HIV positive people compared with 0.4 cases per person-year in HIV negative people. Recurrence and relapse were less likely in those who received 36 weeks or more of TB therapy. The authors recommended that HIV/TB-coinfected people should receive either a longer course of TB treatment or regular follow-up to check for relapse. The study results were published in the November 15, 2001 issue of Clinical Infectious Diseases.

AIDS Drugs Appear Safe During Early Pregnancy

Patricia Garcia, MD, MPH, of Northwestern University in Chicago and colleagues presented data at ICAAC showing that antiretroviral drugs do not appear to cause birth defects when taken during the first trimester (three months) of pregnancy, a period in which early structural development of the fetus takes place. The researchers analyzed data from the Antiretroviral Pregnancy Registry, a voluntary registry of pregnancy outcomes in women receiving anti-HIV treatment. From the time of the establishment of the registry in 1989 to the analysis in 2001, there were 2,209 assessable pregnancy outcomes (92% live births, 2% spontaneous abortions, 2% induced abortions, and 1% stillbirths).

No evidence of an increased rate of birth defects was seen in women using antiretroviral drugs. Birth defects occurred in 2.4% of pregnancies in which the woman took antiretroviral drugs during the first trimester and 2.2% of pregnancies in which the woman started treatment in the second or third trimester. This is comparable to the known birth defect rate of 3% in the general population. Among women taking AZT (Retrovir) during the first trimester, birth defects were seen in 2.2% of pregnancies; the rate among women taking 3TC was 2.7%. Sufficient data were not available to calculate similar rates for other specific antiretroviral drugs. The findings are preliminary due to the low number of pregnancy outcomes reported to date. Physicians may report cases to the registry by calling 800-258-4263.

Caution is still warranted concerning the use of drugs during pregnancy, as evidenced by a report in the December 2001 issue of the journal Sexually Transmitted Infections showing that Pneumocystis carinii pneumonia (PCP) prophylaxis combined with antiretroviral therapy appears to increase the rate of birth defects. In a small study of 195 HIV positive pregnant women, Eva Jungmann, MD, of St. Thomas' Hospital in London and colleagues found that three of 13 infants (23%) born to women taking both anti-PCP and anti-HIV therapy during the first trimester were born with congenital abnormalities. In contrast, no birth defects were seen in the 34 infants born to women who took only anti-PCP drugs or only antiretroviral drugs. Folate (folic acid) is a vitamin that reduces the occurrence of neural tube birth defects when taken during pregnancy; anti-PCP drugs are known folate antagonists and may deplete levels of the vitamin in the body. However, an increased risk of birth defects was not seen in this study among women who took only anti-PCP drugs without antiretrovirals. Women with HIV who require PCP prophylaxis should discuss folic acid supplementation with their physicians.

Malaria Drug and HIV in Breast Milk

According to research published in the November 23, 2001 issue of AIDS, a cheap and widely available antimalaria drug may help reduce mother-to-child (perinatal) transmission of HIV via breast-feeding. Andrea Savarino, MD, of the Università di Torino in Italy and colleagues found in laboratory studies that chloroquine, a drug commonly used to prevent and treat malaria, accumulates in the breast milk. Several studies have indicated that chloroquine inhibits HIV replication, including one published in the same issue of AIDS (also by Dr. Savarino and colleagues) showing that chloroquine alters the HIV gp120 envelope glycoprotein. The researchers suggested that women taking chloroquine may be able to reduce the chances of transmitting HIV to their infants through breast-feeding. They are planning to conduct a human trial of chloroquine in sub-Saharan Africa, where such an inexpensive drug with few side effects could have a considerable impact on perinatal HIV transmission. Johan Boelaert, MD, a member of the research team, noted that because malaria does not carry the same stigma as AIDS, nursing mothers could use chloroquine without fear of revealing their HIV status.

PI Regimens Effective in Children

Results of a four-year study published in the November 22, 2001 issue of the New England Journal of Medicine showed that PI-based combination regimens are effective in children, reducing the rate of death by about two-thirds. Stephen Gortmaker, PhD, and colleagues from the Harvard School of Public Health in Boston, Massachusetts, looked at 1,028 HIV-infected children and adolescents (participants in Pediatric AIDS Clinical Trials Group study 219) who were treated for HIV disease at 40 U.S. pediatric AIDS centers. In 1996 only 7% of the children were receiving PI-based regimens, compared with 73% in 1999; over the intervening period, the AIDS death rate fell from 5.3% to 0.7%.

Rare HIV Infection from Donated Blood

A Texas man recently was identified as the first person known to have contracted HIV from donated blood since blood banks widely adopted a new screening technology three years ago. David Autry of Chilton was infected through donated blood he received during emergency heart bypass surgery in August 2000. Officials with the South Texas Blood and Tissue Center in San Antonio-where the HIV-infected blood originated-said that the blood bank had traced and located all the infected blood, and that no one other than Autry had received blood from the donor in question or contracted the virus. The blood of the donor-who had given blood regularly in the past-did not test positive for HIV until December 2000; the blood bank then went back through its records and notified hospitals that previously had received blood from the donor.

The new nucleic acid-based blood test detects HIV genetic material rather than antibodies. It is more reliable because antibody-based screening tests cannot detect HIV infection during the several-week to several-month "window period" after exposure but before the immune system has produced enough antibodies to register on the test. However, there remains a slight possibility that even the new test cannot detect HIV in the blood of people who were infected very recently, as apparently happened in the Texas case. With the new technology, experts estimate that there is only a one in 2 to 3 million chance of contracting HIV from donated blood. Although widely used, the nucleic acid-based test has not yet been approved by the FDA.

Liz Highleyman is a freelance medical writer based in San Francisco.

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