HIV-1 and HIV-2 coinfection: viral response to HAART differs

Michael Carter
Published: 06 June 2005

For patients coinfected with both HIV-1 and HIV-2, both viruses should be taken into account when selecting treatment regimes and measuring outcome, emphasise investigators writing in the July 15th edition of Clinical Infectious Diseases (now on-line). These cautions are included in a case report of an individual, coinfected with HIV-1 and HIV-2, who initially achieved good immunological and virological outcomes on commencing highly active antiretroviral therapy (HAART). However, the individual experienced an increase in HIV-2 viral load and fall in CD4 cell count after HAART was changed to a simpler regimen which kept HIV-1 undetectable.

HIV-2 has a low prevalence outside west Africa and clinical experience of treating of HIV-2 is limited. Generally, clinicians approach the treatment of HIV-2 in the same way as HIV-1 with minor modifications.

Nevertheless, it is known that HIV-2 is naturally resistant to all currently available drugs in the NNRTI class and that some other antiretrovirals work less well against HIV-2 than against HIV-1.

In November 2001 a 44 year old woman from Guinea Bissau was diagnosed with both HIV-1 and HIV-2 in Madrid, Spain. At the time of diagnosis her CD4 cell count was 112 cells/mm3, and her HIV-1 viral load was 3700 copies/ml. She started a HAART regimen consisting of d4T (stavudine, Zerit), 3TC (lamivudine, Epivir)and Kaletra (lopinavir/ritonavir) two weeks after diagnosis which rapidly suppressed her HIV-1 viral load to below 50 copies/ml. Over the next 19 months her CD4 cell count increased to over 500 cells/mm3 and her viral load remained undetectable.

In the summer of 2003, the patient switched to a once-daily HAART regimen consisting of ddI (didanosine, Videx) tenofovir (Viread)and efavirenz (Sustiva). Despite good adherence, the woman’s CD4 cell count fell steadily and was only 169 cells/mm3 by May 2004. This prompted further changes in the individual’s HIV therapy. Because of concerns that the combination of ddI and tenofovir can suppress CD4 cell count, tenofovir was replaced by 3TC. As her CD4 cell count still did not change, efavirenz was replaced by Kaletra. After three months treatment was again changed to 3TC, Kaletra and atazanavir (Reyataz). Nevertheless, the woman’s CD4 cell count remained low.

All treatment decisions were guided by HIV-1 viral load and HIV-2 viral load was not considered. Investigators conducted a retrospective analysis of HIV-2 viral load using a new real-time nucleic acid sequence based amplification (NASBA). HIV-2 viral load was a little under 7500 copies/ml when the women was first diagnosed with HIV and fell to undetectable during the first 18 months of HIV treatment. However, it started to increase in April 2003 and in all subsequent samples HIV-2 was detectable, reaching a peak of 6800 copies/ml. After therapy with 3TC, Kaletra and atazanavir (Reyataz) was initiated, HIV-2 viral load fell sharply to 91 copies/ml.

Further analysis indicated that the woman was infected with wild-type HIV-2 before the initiation of HAART, but after 23 months of treatment she had developed K65R and I118V resistance mutations in the HIV-2 reverse transcriptase. Finally, the investigators conducted phylogenetic analysis which showed that the patient was infected with HIV-2 subtype A.

“Our patient further illustrates that, in HIV-1 - HIV-2 coinfected individuals, both viruses should be taken into account when assessing treatment decisions and outcomes” conclude the investigators. They add, “drugs known to be active against HIV-2 should be given and periodic measurement of HIV-2 loads must be performed.”

Reference

Rodes B et al. Viral response to antiretroviral therapy in a patient coinfected with HIV type 1 and type 2. Clin Infect Dis 41 (on-line edition), 2005.