July 2001

Potent protein may prevent HIV infection

CAMBRIDGE, Mass. — A newly designed protein that binds to a region of HIV cells may inhibit its entry into human cells.

Researchers at the Whitehead Institute said the new protein, called 5-Helix, binds to the gp41 coat protein of the HIV cell and prevents many strains from fusing to human cells. The so-called “entry inhibitor” would be a viable alternative to current HIV drugs which operate only after cells have already been infected.

Lead researcher Peter Kim, PhD, is hoping 5-Helix can be used as a salvage therapy for patients who have failed a regimen. But the protein may also be useful as a prophylactic that could prevent HIV infection after accidental needle sticks in the hospital setting. Although 5-Helix will be an injected drug, it could probably be self-administered the same as insulin or erythroprotein.

Two years ago, Kim and colleagues used X-ray crystallography to map the gp41 protein. They found that gp41 lies just beneath the surface of the virus coat. But as HIV prepares to enter the cell, a “fusion peptide” protein shoots toward the host cell membrane, temporarily exposing gp41. It is at that moment researchers hope that 5-Helix will bind to the exposed protein and inhibit its ability to enter the host cell.

In vitro testing, 5-Helix showed the ability to prevent HIV from entering cells, even at low-level concentrations. Researchers said 5-Helix is very stable, making it less likely to be degraded by the body’s enzymes, can be made large enough to avoid elimination by the kidney and modified so as to escape destruction by the body’s immune system.

CDC reviews perinatal HIV prevention guidelines

ATLANTA — A recent CDC evaluation (MMWR. 2001;50[RR06]:15-28) of perinatal HIV prevention guidelines found that although the benefits of zidovudine (AZT, Retrovir, GlaxoSmithKline) have been widely disseminated, avoidable perinatal transmissions still occur.

Overall, the implementation of guidelines for AZT use was rapid and effective in most states. By 1996, all but 20% of HIV-positive women had received a diagnosis before delivery. The CDC recommends enhance surveillance in all states to monitor the effect of prevention programs. Perinatal transmission can be eliminated as a public health threat, the report said, through continued use of AZT, increased prenatal care visits and obstetric procedures such as elective cesarean delivery.

The CDC announced guidelines for the use of AZT in the perinatal clinical setting in 1994 and suggested counseling and voluntary testing in 1995. In a survey of 1,321 mother-child pairs from 1993, 1994 and 1996 showed that use of prenatal, intrapartum and neonatal AZT increased from 1993 to 1996. A total of 84% of women who had between 2 and 4 prenatal care visits were prescribed AZT, 89% who had between 5 and 9 visits and 95% of women who had more than 9.

Moreover, the proportion of women who were first tested or diagnosed during pregnancy dropped from 51% in 1993 to 47% in 1996. Only 14% of women received 0-1 prenatal care visits and 19% initiated prenatal care in the third trimester. Women using drugs during pregnancy was a significant predictor of little or no prenatal care (36% vs. 5%).

The CDC recommends specific intervention programs aimed at this high-risk population.

Drug-resistant HIV strain can elude detection

SCOTTSDALE, Ariz. — Researchers think they have found a strain of HIV that can avoid being detected by most resistance tests.

A mutation in the genetic code of HIV at position 318 can make the virus highly resistant to some non-nucleoside reverse transcriptase inhibitors (NNRTI). Most resistance tests, researchers said, cannot detect mutations located beyond position 300. Scientists at Tibotec-Virco announced the findings at the 5th International Workshop on HIV Resistance and Treatment Strategies held here recently.

The research team looked at thousands of HIV samples taken from clinical practices from around the world. They were able to identify around 500 samples with the 318 mutation. Of those, 98% displayed significant resistance to delavirdine (Rescriptor, Agouron). In combination with other mutations, 318 can increase resistance to efavirenz (Sustiva, DuPont).

Two years ago, researchers identified a mutation at position 333 that can cause dual resistance to lamivudine (Epivir, 3TC, GlaxoSmithKline) and AZT. Like the recently discovered mutation, the 333 mutation can evade detection on most resistance tests.