CROI: Aciclovir therapy for women with HIV and herpes produces modest reductions in genital viral load

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Two studies using aciclovir in women co-infected with HIV and genital herpes (HSV-2) presented last week at the Fourteenth Conference on Retroviruses and Opportunistic Infections in Los Angeles showed declines in HIV viral load in their vaginal secretions. But these were quite modest, being almost within the error range of viral load testing, and the findings suggest that using aciclovir as suppressive therapy may only have a modest accessory role in the reduction of HIV transmission.

The use of aciclovir has been previously suggested as an aid to HIV prevention because herpes co-infection, particularly if it is symptomatic, appears to increase the risk of both HIV acquisition and of transmission 2-5 fold.

A study originally presented at last year’s CROI, using the related drug valaciclovir, had produced a 0.5 log (threefold) drop in plasma viral load in African women (see Nagot). It was hoped HSV-suppressive treatment would have a similar effect on viral load in vaginal fluid.



A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.


Short for logarithm, a scale of measurement often used when describing viral load. A one log change is a ten-fold change, such as from 100 to 10. A two-log change is a one hundred-fold change, such as from 1,000 to 10.

herpes simplex virus (HSV)

A viral infection which may cause sores around the mouth or genitals.


The fluid portion of the blood.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

At this year’s CROI, a Thai study (Dunne) which gave aciclovir to women co-infected with HIV and HSV-2, showed a 0.44 log (about 2.8-fold) drop in the HIV viral load in cervicovaginal secretions. This was statistically significant though, as one questioner commented, it is not greatly in excess of the 0.3 log sensitivity limit of most viral load tests.

However a South African study (Delany) only produced an average 0.12 (11%) drop in vaginal viral load, which was not statistically significant, though it produced an average 0.37 log (2.4-fold) drop in plasma HIV viral load, and also significantly reduced the number of visits at which women shed detectable amounts of HIV in vaginal fluid, which may be a more useful measure of their infectiousness.

The Thai study was a randomised placebo-controlled double-blind crossover study. What this means is that of the 76 women enrolled, 34 were given a month of twice-daily aciclovir (800mg), then after a month’s ‘washout’ on no treatment, they were given a month on a placebo pill. The other 33 received the placebo pill first, then the washout, and then the aciclovir.

Cervicovaginal lavage (CVL) specimens were obtained from enrolled women at baseline and at weekly visits for three months. The viral load test used for the CVL specimens could detect viral load down to a threshold of three copies of HIV per ml.

The women were aged 18-49 with an average age of 33 and had been diagnosed with HIV for an average of 4.6 years. None were taking antiretrovirals. All had CD4 cell counts over 200 cells/mm3 with an average count of 366 cells/mm3. Their average HIV plasma viral load was 40,000 copies/ml and their average CVL viral load was quite low at 63 copies/ml, though this varied from undetectable to 12,500 copies/ml. Three-quarters of the women had detectable CVL viral load at baseline, though only two (3%) had detectable HSV shedding at baseline.

However three women required aciclovir therapy for genital ulcer disease during the study.

One-third of the women had no change in their CVL viral load while on aciclovir, though these were mainly women who had undetectable levels on entry to the study. Thirty-four women (55% of those who completed the study) had a reduction in their CVL viral load averaging 0.44 log (2.75-fold). Six women actually had an increase in CVL viral load while on aciclovir.

However the thirty-four women (55% of those who completed the study) whose viral loads did go down had a reduction in their CVL viral load averaging 0.44 log (2.75-fold).

In questioning, investigator Eileen Dunne said that plasma viral loads were not measured during the study so they could not be correlated with CVL viral load, though this would be done retrospectively. She was also asked if this relatively modest drop in CVL viral loads that were mainly low in the first place would have much impact on transmissibility of HIV. She said that the impact of aciclovir therapy on HIV transmission might be greater in women who had symptomatic HSV lesions, especially if given in combination with antiretroviral therapy.

In the South African study, 269 women were randomised to receive either 400mg of aciclovir (151 women) or a placebo (148 women) for three months. Women with genital ulcers or other reasons to get open-label aciclovir therapy were excluded from the study, though in questions afterwards it became clear that a few women had received episodic therapy for genital ulcers during the trial. Investigator Sinead Delany said that they did not see substantial numbers of women returning for episodic therapy in the placebo arm, but this could have slightly blunted the results.

The women gave blood tests and vaginal swabs at the end of the first, second and third month.

The women’s average age was 32 and average time since HIV diagnosis was just over a year. The CD4 count in the aciclovir arm was 446 cells/mm3 and in the placebo arm was 500 cells/mm3 (women with CD4 counts under 250 cells mm/3 were excluded from the study). Their average HIV plasma viral load was 12,500 copies/ml. A total of 107 women in the aciclovir arm and 104 in the placebo arm shed detectable amounts of HSV-2 vaginally at the start of the study.

The vaginal viral load in the women on aciclovir was only 0.12 log (11%) lower than in the women on placebo, and this was not statistically significant (p=0.3).

However, somewhat fewer women on aciclovir shed detectable amounts of vaginal HIV at every visit (23% versus 30%) and there was a statistically significant reduction of 44% in the number of times women shed detectable HIV during their three follow-up visits. More aciclovir recipients shed no HIV at any visit than women on placebo.

There was also a 0.37 log (42%) reduction in plasma viral load amongst the women on aciclovir, and this was statistically significant. The plasma viral load in women on aciclovir was 4,700 copies/ml and in women on placebo 8,300 copies/ml.

Genital HSV-2 shedding was reduced by 58%, and this was statistically significant.

Delany said that her study provided “weak evidence for an overall effect on HIV genital viral load…but stronger evidence for a reduction in frequency of shedding.”


Nagot N et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med 356: 790-799, 2007.

Dunne E et al. The effect of suppressive aciclovir therapy on HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 30, 2007.

Delany S et al. Impact of HSV-2 suppressive therapy on genital and plasma HIV-1 RNA in HIV-1 and HSV-2 seropositive women not taking ART: a randomised, placebo-controlled trial in Johannesburg, South Africa. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 154LB, 2007.