HIV drug resistance can persist three years after transmission

Edwin J. Bernard
Estimated reading time 3 minutes
This article is more than 22 years old.

Researchers in Vancouver, Canada have identified two separate cases of transmission of antiretroviral-resistant HIV where resistance mutations have persisted for up to three years. These drug-resistant viruses were unusual in that they remained fit (i.e. able to replicate and therefore, destroy CD4 cells), did not revert to wild type drug sensitive HIV (which is usually seen when HIV is not under pressure from antiretrovirals), and rendered the two individuals infected with the mutated virus less susceptible to treatment, leading to more rapid disease progression.

The researchers had detailed data on both the infected individuals (the index cases) and the individuals that infected them (the source cases).

Index case 1 was infected with HIV through intravenous drug use in June 1998 and remained off therapy from seroconversion to March 2001. Genotype studies of source case 1 at the time closest to the seroconversion of index case 1 (April 1998) showed that this person’s HIV had the following mutations: 10I, 20R, 36I, 63P, 71V, 82A. 90M (protease inhibitor mutations); 41L, 44D, 75M, 98G, 210W, 215Y (reverse transcriptase mutations). After stopping all therapy in March 1998, source case 1’s HIV reverted to wild type within seven months. In July 1998, within weeks of transmission, index case 1’s HIV had the same protease mutations and four reverse transcriptase mutations, including one that had been dominant in source case 1 a year previously (98G), and one that had mutated from 215Y to 215C. By March 2001, after no antiretroviral treatment, the protease inhibitor mutations remained the same and there were now six reverse transcriptase mutations (41L, 44D/E, 75M/V, 98G, 210W, 215S). CD4 cell count had declined from 680 cells/mm3 in April 1999 to 240 cells/mm3 in March 2001. Viral load peaked at 238,000 copies/ml in August 2000 and was 116,000 copies/ml in March 2001.

Glossary

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

CD4 cells

The primary white blood cells of the immune system, which signal to other immune system cells how and when to fight infections. HIV preferentially infects and destroys CD4 cells, which are also known as CD4+ T cells or T helper cells.

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 

natural history

The natural development of a disease or condition over time, in the absence of treatment.

Index case 2 was infected with HIV by their sexual partner in January 2001. Genotyping of source case 2’s HIV prior to their infecting index case 2 (5 January 2001) showed that two reverse transcriptase mutations were present: 190A, and 219K/Q. Between January and July 2001 (last data available) index case 2’s HIV also had a persistent 190A mutation and there was a rapid CD4 cell decline from 660 cells/mm3 in January to 330 cells/mm3 in May, with a persistent viral load around 130,000 copies/ml. This could have been due to the effects of primary infection, however, and since index case 2 began antiretroviral therapy in late June 2001, the natural history of the mutation could not be seen.

However, the authors argue that index case 1 shows that without a pre-existing viral reservoir of wild type HIV, new transmission of drug-resistant virus can persist for much longer than previously thought, leading to further complications in treatment and a less positive prognosis. This “suggests that resistance testing should be considered before treatment in the chronically infected and treatment-naive patient,” they conclude.

Further information on this website

Transmission of drug-resistant HIV: summary of research to date

References

Chan KCW et al. Prolonged retention of drug resistance mutations and rapid disease progression in the absence of therapy after primary HIV infection. AIDS 17 (8): 1256-1258, 2003.

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