HIV superinfection: man infected with wild-type four months after drug-resistant strain

This article is more than 21 years old.

A Californian man has been superinfected with wild-type (drug-sensitive) HIV after initial infection with drug-resistant virus. The case is reported in a fast tracked article in the May 2nd 2003 edition of AIDS.

The case adds to the growing body of research on HIV superinfection.

The patient was enrolled in a cohort of people who were initially infected with drug-resistant HIV. Four months later, however, a separate and distinct wild-type viral population was detected.

Glossary

strain

A variant characterised by a specific genotype.

 

superinfection

When somebody already infected with HIV is exposed to a different strain of HIV and becomes infected with it in addition to their existing virus.

 

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

plasma

The fluid portion of the blood.

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). 

At enrollment the man had a CD4 cell count of 711 cells/mm3 and viral load of 2,413 copies/ml. Plasma and peripheral blood mononuclear cell samples were taken in order to identify resistance mutations. Resistance mutations in reverse transcriptase codons 181 and 184 were identified.

However, the presence of a second, distinct viral population was confirmed four months later by the sequencing of the 1302 bp fragment of the gag-pol region. It showed that, unlike the initial strain of HIV detected in the man, the second strain was drug-sensitive at codons 181 and 184 of HIV reverse transcriptase where drug resistance was initially detected.

Both strains of HIV were from the type B sub type, which is prevalent in the US. Further tests were conducted to rule out the possibility that the man had been initially infected with both a drug-sensitive and drug-resistant strain of HIV. These included clonal sequencing and genetic reconstruction of viral populations. These tests failed to detect a mixed population of HIV before or after the point at month four when the man was superinfected. Coinfection was further ruled out by analysis of the length polymorphism of the V4-V5 region of HIV gp120 which showed that the man was initially infected with a single strain of HIV.

Superinfection with the wild-type HIV had a negative impact on the man’s viral load and CD4 cell count. Coinciding with detection of the second strain of HIV the man’s viral load increased from a stable level of between 2,400 copies/ml and 7,000 copies/ml to a little over 34,000 copies/ml at month four, almost 200,000 copies/ml at month six and 170,000 copies at month nine. At the same time, the man’s CD4 cell count fell from almost 800 cells/mm3 to a low point of 283 cells/mm3 at eleven months.

"These data indicate that four months after infection by drug-resistant HIV this patient was infected by a second, drug-sensitive virus”, note the investigators.

The potential health implications of infection with two different viral populations, which are not equally susceptible to the patient’s immune system, are emphasised by the investigators, with the fitter wild-type virus causing “an abrupt increase in plasma viremia” in this patient.

Superinfection could also impact on the effectiveness of HAART. Standard tests to detect drug resistance would not reveal a drug resistant strain of HIV after superinfection with a second, fitter, wild-type strain. “Nevertheless, if the patient were to initiate therapy, it seems likely that drug-resistant virus would quickly re-emerge.”

Further information on this website

Transmission of drug-resistant HIV - overview

First unequivocal case of HIV superinfection -news story

Superinfection with HIV: evidence published -news story

HIV superinfection: more evidence - news story

Resistance - booklet in the information for HIV-positive people series

References

Koelsch KK et al. Clade B HIV-1 superinfection with wild-type virus after primary infection with drug-resistant clade B virus. AIDS, 17: F11 – F16, 2003.