AIDS TREATMENT UPDATE, Issue 39, March 1996
Edward King

An updated analysis of the Delta trial results extended the preliminary results reported last year. Among previously untreated people, those taking AZT plus either ddI or ddC lived significantly longer than those taking AZT alone. The latest figures suggest that the AZT/ddI combination may be somewhat more effective than AZT/ddC at delaying disease progression (abstract LB5).

The more complete results now show that among people who had already taken AZT, those who switched to AZT plus ddI had marginally improved survival compared with people who remained on AZT alone. Switching to AZT plus ddC had no significant effect on survival.

American researchers reported the results of the CPCRA 07 trial (also known as NuCombo), which was identical to Delta except that it enrolled people with more advanced HIV infection. The 1,113 participants had AIDS or CD4 counts below 200. The results were similar - previously untreated people had a lower rate of disease progression or death if they took combination therapy rather than AZT alone, but there was no significant difference between the combinations versus AZT monotherapy in AZT-experienced people (abstract LB4).

* 3TC side-effects

Canadian doctors reported that 3TC may cause more serious side-effects than previously reported among people with advanced HIV infection (abstract 134).

Among 36 people taking 3TC alone or in combination with other anti-HIV drugs in an expanded access scheme, half reported some side-effects that were attributed to 3TC, and 20% stopped taking 3TC because of toxicities. Five people (14%) suffered hair loss, five developed nerve inflammation and several others experienced blood abnormalities, nausea or vomiting.

* CMV prophylaxis

People who have detectable cytomegalovirus (CMV) in their blood may be the most likely to benefit from drugs to prevent the onset of CMV disease. Researchers analysed data from the study ACTG 204, which compared the effectiveness of high dose acyclovir versus valaciclovir for preventing CMV disease in people with low CD4 counts (abstract 10).

All the trial participants had antibodies to CMV in their blood, but researchers also used the PCR test to detect the virus itself in their blood or urine. The people in whom valaciclovir reduced the risk of CMV disease were mainly those who had detectable CMV in their blood when they joined the trial.

British doctors say that the cost of anti-CMV drugs such as oral ganciclovir means that they cannot afford to offer it routinely to everyone with low CD4 counts. They hope that tests such as this may eventually help to target CMV prophylaxis by identifying the sub-group of individuals with low CD4 counts who will benefit from prophylaxis.

* Stavudine plus ddI

The combination of stavudine (d4T) plus ddI has good anti-HIV effects, according to interim results from a trial in previously untreated people with CD4 counts between 200 and 500 (abstract 197).

Among 32 people who completed 6 months of treatment with the combination, 19 experienced a one log drop in viral load at week 28, and 10 had a 2 log reduction. Among the 14 people who have received the combination for a year, the drop in viral load at week 52 averaged 1.5 log. The average CD4 count remained 60 cells above baseline after a year's treatment.

There had been concerns that this combination would result in a high rate of peripheral neuropathy, since both drugs can cause this side-effect. In fact, the rate of peripheral neuropathy has been similar to that seen with either drug alone. Stavudine is a licensed drug in the USA; in the UK it is available through an expanded access scheme.

* Mother-to-baby transmission

Viral load measurements are an imperfect indicator of the risk that an HIV-positive pregnant woman will pass on the virus to her unborn child, according to several studies.

When researchers analysed the plasma viral load of pregnant women whose children were infected with HIV, compared with women whose children were uninfected, they found no clear link. Some women with very high viral load had uninfected children, while some women with very low viral load had infected children (abstracts LB1-LB3).

A better predictor of the risk of transmission seems to be the woman's CD4 count, although this too is imperfect. A woman with a low CD4 count is significantly more likely to pass on HIV to her child.

The American trial ACTG 076 found that AZT treatment during pregnancy, labour and the infant's first weeks of life can reduce the risk of HIV transmission by about two-thirds. Doctors in North Carolina reported that these trial results hold true in the real world: the infection rate among children of HIV-positive women in the State has fallen from 21% in 1993 to 8.5% in 1994 (abstract 25).

Mother-to-baby HIV transmission has been linked to vitamin A deficiency among pregnant women in Africa, leading to suggestions that vitamin A supplements may be useful for all HIV-positive women. However, vitamin A deficiency is rare in developed countries, and excessive intake of vitamin A during pregnancy may increase the risk that the child will have birth defects. An American study found no evidence of a link between low vitamin A levels and mother-to-baby transmission among 96 American women, suggesting that this may not be a risk factor in the USA and similar countries (abstract 506).

* Doctors' experience

The more experience your doctor has at treating people with AIDS, the longer you are likely to live (abstract 413).

The study analysed the medical records of over 400 people treated by 125 different doctors in the Seattle area. People with the most experienced doctors survived 26 months after being diagnosed with AIDS, compared with 14 months for those with the least experienced doctors.

The most experienced doctors were more likely to monitor CD4 counts regularly and to prescribe PCP prophylaxis, resulting in significantly fewer cases of PCP and prolonged life.

CONFERENCE ABSTRACTS

The abstracts for these studies and all the other research presented in Washington can be read on the Internet at http://www.idsociety.org

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