Treatment with HAART does not significantly reduce the shedding of herpes simplex virus type 2 (HSV-2) according to a US study to be published in the August 15th edition of The Journal of Infectious Diseases (now available on-line). The investigators did however find that the use of HAART reduced the number of days HAART treated individuals had ulcers caused by HSV-2, but caution that the high rates of HSV reactivation seen in their study could facilitate the transmission of HIV and recommend that HIV-positive individuals coinfected with HSV-2 continue to take anti-HSV therapy even when on HAART.
HAART has been shown to restore the immune system’s ability to fight opportunistic infections caused by herpes viruses including CMV and HHV-8. Infection with HSV-2 is widespread among HIV-positive individuals (studies suggesting a prevalence of 50%-95%), and HIV is frequently detected in genital ulcers caused by HSV-2, increasing he risk of HIV transmission.
No studies have, however looked at the impact of HAART on either the shedding of HSV-2 in the mucosa of HIV-positive individuals or the development of ulcers caused by HSV-2 in HAART-treated patients.
Investigators in Seattle enrolled 77 HIV-positive individuals, all of whom were infected with HSV-2 into a study to answer these questions.
On entry to the study, 28 patients were taking HAART (median duration of anti-HIV treatment being 21 months). Individuals were allowed to take anti-HSV treatment in the event of an attack causing ulcers, but were not allowed to take HSV suppressive therapy.
CD4 cell counts were comparable between the patients taking HAART and those not on HIV treatment (332 cell/mm3 versus 307 cellmm3), but HIV viral load was significantly lower in patients taking HAART (median 170 copies/ml versus 18,800 copies/ml, p < 0.001). In total, eleven of the 28 patients taking HAART had a viral load below 50 copies/ml.
All 77 study members collected swabs from oral and genital secretions. Investigators had swabs from 4462 days of follow-up to analyse. In total, HSV secretions were present in 8.4% of oral samples and 27.3% of genital samples.
Frequency of HSV shedding was reduced, but not significantly, amongst HAART-treated individuals (17.7% days versus 29.3% days untreated patients, p = 0.08). HSV viral load was also similar between patients treated with HAART and individuals not taking anti-HIV treatment (p = 0.20).
However, the number of total number of days when ulcers caused by HSV-2 were present was significant lower in the HAART-treated individuals (2.8% of days versus 11.3% of days in patients not taking HAART, p = 0.001).
Investigators also found that individuals with advanced HIV disease were at no greater risk of shedding HSV-2. No relationship was found with either CD4 cell count (p = 0.80), or HIV viral load (p = 0.59).
“Our data indicate that treatment of HIV-1 infected persons with HAART does not significantly reduce the frequency of mucosal HSV shedding in HIV-1-infected persons. However, the percentage of days that subjects reported HSV lesions was reduced among HAART-treated subjects, suggesting that the improvement in clinical HSV disease is more pronounced than the reduction in HSV shedding,” write the investigators.
The investigators believe that their findings could have implications for HIV prevention. “The high frequency of HSV reactivation and the marked up-regulation of HIV-1 in HSV-infected cells all suggest that HSV reactivation may continue to facilitate the transmission of HIV.”
Anti-HSV prophylaxis should be continued in HIV-positive individuals coinfected with HSV even if they have a high CD4 cell count and are taking HAART, the investigators conclude.
Posavad et al. Frequent reactivation of herpes simplex virus among HIV-1-infected patients treated with highly active antiretroviral therapy. Journal of Infectious Diseases 190 (on-line edition), 2004.