Published in the Bulletin of Experimental Treatments for AIDS April 1998 issue, by the San Francisco AIDS Foundation.

Selected Highlights from 5th Conf. on Retroviruses and Opportunistic Infections Main Page

• New Anti-HIV Drugs
• Hydroxyurea
• Protease Inhibitor and Other Drug Combinations
• Opportunistic Infections
• Miscellaneous

April 1998 Table of Contents

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April 1998

Selected Highlights from the 5th Conference on Retroviruses and Opportunistic Infections

Miscellaneous

Harvey S. Bartnof, MD

Explanation Uncovered for Ineffective d4T or 3TC Therapy Following Use of AZT

Jean-Pierre Sommadossi, PhD, and colleagues from the University of Alabama have found an explanation for a heretofore unexplained phenomenon. It had been observed that anti-HIV drug-naive HIV positive patients treated with d4T plus 3TC experience a much larger HIV RNA viral load decrease than patients who had previously experienced failure of AZT-based therapies and subsequently switched to d4T plus 3TC. No significant genotypic changes could be found to explain the decreased response. Also, blood plasma tests revealed adequate drug levels of both d4T and 3TC. However, by measuring the activated metabolites of d4T and 3TC, that is, triple phosphorylates within blood mononuclear cells, Sommadossi found decreased levels in those who had previously experienced failure of AZT-containing therapies, when compared with those who were drug-naive and had a greater viral load decrease. The underlying mechanism for a decrease in intracellular phosphorylation of d4T and 3TC is under investigation. The authors concluded that intracellular levels of the active metabolites of d4T and 3TC correlate with blood plasma HIV viral load decreases.

It is difficult to draw specific conclusions from these findings, particularly in terms of the order in which to use anti-HIV therapies. For example, some people may conclude that the results suggest that d4T should be used as a first-line therapy. However, the converse of the report's conclusions was not tested. Specifically, it was not determined whether failure of a previous d4T-containing regimen would lead to subsequent failure of an AZT-containing regimen. It is possible that this would be the case. The study does help us understand specific mechanisms of HIV drug failure. Future assessments of anti-HIV drug efficacy may include intracellular drug measurements.

Sommadossi JP and others. Impairment of stavudine phosphorylation in patients receiving a combination of zidovudine and stavudine. CROI. Abstract and oral presentation 3.

Most Multiply Exposed HIV Negative Partners Have Normal CCR5 Gene

Previous research had suggested that some HIV negative gay men who had had multiple, unprotected sexual exposures to HIV were resistant to infection due to a double mutation in the CCR5 co-receptor gene. Now, researchers from the University of Washington have determined that 70% of such persons whom they have analyzed have normal CCR5 co-receptor genes. Among their 37 HIV negative, multiply-exposed study participants, only 3% (1 of 37) carried a double CCR5 mutation. Another 27% (10 of 37) had 1 copy of the mutant gene, while the remaining 70% (26 of 37) had 2 normal copies of the CCR5 genes. All 37 had negative polymerase chain reaction DNA tests for HIV.

The authors found that 46% of those with 2 normal CCR5 genes had a cytotoxic T-cell lymphocyte (CTL) response in vitro using samples of their blood mononuclear cells and HIV antigens. And 10% (1 of 10) of individuals with 1 CCR5 mutation also had a CTL response in vitro.

The authors concluded that inheriting mutant CCR5 genes did not account for the majority of HIV-1 resistance in their study. CTL responses and other factors may have a role in resistance to HIV transmission. Understanding the role of these factors will provide additional insights to new therapies and vaccine candidates.

Markee J and others. Protection against HIV-1 infection in persons with repeated exposure: evidence for T cell immunity in the absence of inherited CCR-5 co-receptor defects. CROI. Abstract 537.

HIV Documented from 1959

The first occurrence of HIV/AIDS has been debated since the disease was first recognized. In the 1980s, there was a published report of a patient whose blood plasma collected in 1959 was found to contain HIV antibodies. However, several researchers questioned the validity of the sample results. Now, researchers from the Aaron Diamond AIDS Research Center in New York have analyzed the stored plasma sample by amplifying and characterizing viral genetic sequences. David Ho, MD and his colleagues "not only authenticate this case as the oldest known HIV-1 infection, but also place its viral sequence near the ancestral node of (HIV)." Moreover, the researchers suggested that HIV "evolved from a single introduction into the Africa pop-ulation in a time frame not long before 1959." The report was also published in the February 5, 1998 issue of the journal Nature.

Zhu T and others. An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. CROI. Abstract 280; Nature 391:594-597. February 5, 1998.

Page last updated 5 May 1998