SEPTEMBER 1998

NUMBER ONE

NEWS FLASH

Hip-Hop Condoms?
Let's say you're an "extra big" man who complains most condoms are too tight or uncomfortable and just cramp your style. (Never mind that most condoms fit over a hand all the way to the elbow: We believe you.) Now you can turn to the kind folks at Mayer Laboratories in Oakland, California, who have come up with EZON, the "baggy" condom, which fits loosely over the shaft of the penis but is held tightly in place at the base. EZON is made of polyurethane, not latex, so it's not as thick as conventional condoms, but the P.R. guys say it's five times as durable. Now they have to get the government to believe them. FDA approval of EZON is pending. Did I hear someone say "represent"?

Speed and HIV: Double Trouble
A February study published in the Western Journal of Medicine by California researchers found that people who use speed, or oral methamphetamine, have an increased risk of contracting STDs and HIV. The study involved more than 258,500 sexually active patients seeking care at public HIV testing sites, all of whom denied using injection drugs. Those who used speed had a higher number of sexual partners, used condoms less frequently, and were more likely to engage in sex work. Sounding the alarm, researchers have called on HIV advocates to address the HIV risk of speed use in prevention programs. What's the message? Speed may increase risky behavior.

Good News: Short-Course TB
With more than one third of HIV deaths in the world caused by tuberculosis, there's good news on the TB-prevention front. A six-year federal study of almost 1,600 subjects by researchers at the Veteran Affairs Medical Center in Washington, D.C., found that a short two-month, two-drug course of daily rifampin (450-600 mg/day) and pyrazinamide (20 mg/kg daily) produced about the same rate of TB cases and deaths as the standard 12-month preventive regimen of daily isoniazid (300 mg/day). It also produced fewer side effects. The short-course treatment is cheaper, which could really help people in developing nations, where HIV-related TB is a big killer. It can also help prevent active infection in anyone with latent TB.

Unfortunately, dangerous drug interactions could make short-course TB therapy risky for HIV-positive people on HAART or using methadone. Rifampin shouldn't be taken with protease inhibitors (see "When Drugs Fail"); it is a very strong inducer of the p450 3A4 metabolic pathway used by PIs (see P450 table). Rifampin also interacts with methadone. Isoniazid is also a p450 inducer, as is rifabutin, a drug often used as an alternative to rifampin to treat active TB.

There is, however, more good news: After a two-year effort, French and British scientists recently cracked the genetic code for the tuberculosis organism. They're hoping it will lead to new anti-TB treatment and vaccines. In the meantime, Cel-Sci, a biotech company, has developed a vaccine for drug-resistant TB they say produces a more powerful immune response than conventional technologies. Stay tuned.

Hey, Baby!

Almost a million infants are living with HIV in the world now; more than 10,000 live in the U.S. AIDS is now the leading cause of child death in many U.S. cities. Although promising results are being reported with three-drug combinations to treat pediatric HIV, many infants are not getting the benefit of new therapies. This is particularly true of African-American and Latino infants whose families rely on cash-strapped Medicaid and government programs. For now, there are more than 400 special-care centers in the U.S. that provide for children with HIV who cannot access health care.

As with adults, getting early access to testing, care, and treatment can increase a child's chance of survival. New studies show that many children with HIV remain well for years, while others quickly get sick. In a recent 12-year study of more than 3,000 HIV-positive children under 13, Columbia University researchers predicted that almost half will survive to adolescence and 70 percent will live even longer.

Caring for HIV-positive infants is complex and demanding: ideally, a medical team includes physicians, nurses, social workers, psychologists, nutritionists, outreach workers, and pharmacists. If your baby has HIV, consult a pediatrician specialized in HIV care and consider getting a case manager to help your family plan how to get the care and support you will need. Local AIDS organizations can refer you to pediatric specialists and offer other services; clinics and social-service agencies also offer case-management services.

Pediatric HIV Disease: HIV therapy presents many challenges with infants because their young immune systems are vulnerable to infections and because HIV disease progression and drug effects change with age. HIV can infect human fetuses as early as eight weeks after conception; the virus severely affects physical development and the psychological and emotional well-being of infants. Some also suffer from complications of exposure to alcohol, drugs, and sexually transmitted diseases in the womb.

HIV symptoms include failure to thrive, poor growth, slow motor or language development, persistent diarrhea, thrush, recurrent or severe candida diaper rash, swollen lymph glands, and respiratory and bacterial problems. Experts say it's important to monitor an infant's head circumference and growth with weight and height charts and to see an HIV-experienced nutritionist to ensure the child gets a proper diet.

Early HIV Testing: Failure to diagnose maternal-fetal HIV infection remains a problem, say experts, who add that early testing and aggressive treatment can sharply lower the risk of transmission and delay disease progression. Initial testing is now recommended within 48 hours after birth (using PCR viral-load tests) and can be helpful for early detection at 14 days. Avoid taking blood samples from the umbilical cord that may be contaminated with maternal blood. Infected infants can be definitively diagnosed within one month after birth with PCR. For infants under 18 months who test positive, two PCR tests from separate samples are recommended to confirm the results. Diagnostic testing should be repeated at one to two months and three to six months.

If PCR tests aren't available, HIV-antibody tests should be repeated every six months until 18 months of age. Parents and siblings should also be tested. Caution: Past studies showed that all babies born to untreated HIV-positive mothers test positive temporarily after birth, due to the passive transfer of the mother's antibodies. In uninfected infants, HIV antibodies generally disappear after seven to 10 months.

T-cell tests should be obtained as soon as possible after a positive HIV PCR test result and should be repeated every three months.

Viral load: Babies generally have greater viral loads than adults, sometimes reaching millions of HIV copies, similar to primary infection in adults. Without treatment, viral load slowly decreases but levels off at higher rates than in adults. Ongoing studies show that a very high initial viral load is linked to more rapid progression of disease, suggesing that early treatment of infants with high viral loads could slow HIV.

Preventive Therapy: Experts recommend preventive therapy and vaccinations for HIV-positive infants to ward off HIV-related illnesses, especially -respiratory and bacterial infections and oral thrush.

Pneumocystis carinii pneumonia (PCP) is the most common HIV-related infection in infants and children and is treated with Bactrim (Septra), or as a less effective alternative, dapsone, in syrup form or aerosolized pentamidine. Because T-cell counts vary from infant to infant, experts recommend PCP prophylaxis for all HIV-positive infants less than 12 months and for one- to two-year-old infants with T-cell counts below 750; in children aged two to five, if T-cells fall below 500; in children six or older if T-cells fall below 200.

Pulmonary lymphoid hyperplasia (PLH) and lymphoid interstitial pneumonitis (LIP) are the second-most common respiratory infections in infants with HIV. Corticosteroids like prednisone and inhalers can help with breathing but should be used with caution as they stress the heart.

Antiviral Treatment: Federal treatment guidelines for pediatric HIV recommend early, aggressive use of three-drug combination therapy for infants with clinical signs or symptoms of HIV and for those who test HIV positive. These are based largely on initial drug safety, dosing, and efficacy studies done in adults. Drugs are absorbed, used, and eliminated in the body differently in children than adults, making it very hard for pediatricians to predict how particular treatment regimens will work in an infant.

There are currently eight HIV antiviral drugs available for pediatric use, including newcomer Ziagen, available through a broadened expanded-access program. In a recent three-drug pediatric trial of AZT/ddI/nevirapine in eight newborns aged two months to 16 months, researchers found the drugs lowered viral load by 97 percent in seven infants by week four. HIV RNA levels remained "undetectable" after 14 months in two infants.

Adherence: Adherence to drug regimens is needed to offset HIV resistance but poses a special problem for infants who depend on others to administer medicine. For now, the use of oral HIV formulas to treat infants poses a barrier, since they are hard to administer and tolerate, and drug absorption is affected by food. Education of parents, caregivers, and children is needed to stress the importance of compliance with drug regimens and should be reinforced at every visit with the doctor. But caregivers must first address real-life barriers to adherence such as homelessness and poverty.

Toxicity: Children develop side effects and drug toxicities at different frequencies than adults. Crixivan may cause an increase in indirect bilirubin in newborns and infants and must be monitored. Videx (ddI) has been also linked with changes in retinal depigmentation (eye color) in pediatric HIV but causes less risk of pancreatitis in kids. Indinavir can cause kidney stones, but it's harder to make sure infants get enough daily water to reduce this risk. AZT may cause pediatric anemia.

Vaccinations With the following exceptions, most vaccines for children with HIV are the same as for those without: Oral polio vaccine (OPV) and varicella zoster vaccine are not recommended (VZIG, varicella zoster immunoglobulin prophylaxis is used for an initial exposure to chicken pox). Age Vaccine DPT = diphtheria-pertussin-tetanus. IPV = inactivated polio virus HBOC = Haemophilus influenzae b conjugate vaccine; alternatively PRP-OMP, another Haemophilus influenzae b conjugate can be given at two, four, and 12 months. MMR = measles-mumps-rubella dT = adult diptheria and tetanus * Hepatitis B alternative schedule: At birth, one to two months, six to 18 months. If mother is HBsAG positive, infant should receive hepatitis B immune globulin and hepatitis B vaccine. **May give earlier in high-prevalence areas for measles. In New York City, MMR is given at 12 months. MMR booster (age 4-6) should not be given to severely immunocompromised infants. ***A second booster dose is recommended for "high risk" children three to five years after initial dose (five to seven years of age). 2 months DPT, IPV, HBOC. Hep B* 4 months DPT, IPV, HBOC, Hep B 6 months DPT, IPV (or 18 months),HBOC, Hep B, flu (annually, also for family members). 12 months PPD test (Mantoux with anergy screen) 15 months MMR**, HBOC, DPT, IBV 24 months Pneumococcal vaccine*** 4-6 years DPT, IPV, MMR 14-16 years dT, measles

Newborn Drug Scare NUMEROUS REPORTS TO DATE HAVE FOUND THAT USING AZT is safe for pregnant women, causing mild side effects like anemia (AZT) or high bilirubin in newborns. But an alarming Geneva late-breaker report has raised a cautionary red flag on the safety of drug combinations. Swiss researcher Patrizio Lorenzi found that 21 of 37 pregnant women on combinations of either AZT/3TC/Crixivan or d4T/3TC/Crixivan reported adverse events. Most were mild, but more severe ones included premature birth in 17 of 30 babies. Two newborns had non-life-threatening intracerebral hemorrhage and one had a major malformation. In an interview, Dr. Lorenzi cautioned against drawing fast conclusions from his study. He said some of the women had histories of IV drug use and advanced HIV infection prior to HIV therapy. One case of brain hemorrhage might have been due to an undiagnosed toxoplasmosis infection. For now, pregnant women are advised to carefully discuss the benefits versus risk of HAART therapy with doctors. For updates, contact the Antiretroviral Pregnancy Registry at (800)-722-9292, ext. 38465.