New investigational topical HERPES SIMPLEX VIRUS (HSV) treatment

We start this week with a novel therapeutic agent for HSV. Khemis et al1 in France highlight the potential role for a novel agent, the CS21 barrier genital gel in the management of recurrent genital HSV. This prospective randomised controlled, investigator-blinded trial compared CS21 barrier genital gel, the investigational agent, with topical aciclovir and a placebo in 61 (43 women and 18 men) patients with recurrent herpes. They compared clinical end points using a cumulative score of four herpes-related functional symptoms (pain, burning, itching and tingling sensation) and secondary endpoints (skin changes, time to heal, local tolerance and overall acceptability of the treatment). CS21 was found to be more efficient than topical aciclovir or placebo for subjective symptoms as measured by a self-reported questionnaire and for pain relief in those with recurrence of genital herpes on days 1, 2, 3, 8, and 15 of use. Significant differences were seen between CS21 and placebo (p=0.003) and CS21 and aciclovir (p=0.024) at day 2. Time to heal was also shorter with CS21 when compared with placebo at 9.62 versus 17.05 days (p=0.04; p=0.057 when compared with aciclovir). Topical aciclovir is not used routinely in the UK (where oral therapy is preferred), but is used by many patients in France, and perhaps in other countries. There may certainly be a role for this agent for patients unwilling to take oral medication, who want effective, speedy symptomatic relief.

Can you hear me ok?

Next, we tackle the slightly overlooked topic of hearing loss in HIV-positive adults. Torre et al2 in the USA looked at pure-tone hearing thresholds in HIV-negative and HIV-positive adults (stable on antiretroviral therapy (ART) with a good CD4 count), to evaulate hearing sensitivity characteristics and assess whether disease status and/or ART were associated with hearing loss. Two hundred and sixty-two men (117 HIV positive) and 134 women (105 HIV positive) were enrolled in the study, recruited from the Multi-center AIDS Cohort Study cohort and the Womens Interagency HIV Study. HIV-negative controls were matched demographically.

HIV-positive adults had poorer hearing sensitivity independent of CD4, HIV viral load (VL), long-term noise exposure, and ART at higher (p=0.02) and lower (p=0.05) pure tone conduction thresholds. In 97% of cases the hearing loss was sensorineural. Most participants were middle aged so the higher frequency loss was anticipated (as a process of ageing) but lower frequency hearing loss was unexpected. This is the frequency at which we hear vowels and consonants and the authors comment that this hearing loss may lead to increased communication difficulties in some HIV-positive individuals. Unfortunately, the authors make no comment of syphilis status which would have been useful information.

HIV acquisition following syphilis acquisition

This interesting paper by Solomon et al3 demonstrates the subsequent HIV seroconversion of those who are diagnosed with syphilis. The rate of syphilis acquisition was studied in the setting of a prospective cohort as part of the Pre-exposure Prophylaxis Initiative (iPREX) trial, where individuals were randomised to receive pre-exposure prophylaxis (PrEP) with Truvada (FTC and Tenofovir) or placebo. Two thousand four hundred and ninety-nine men who have sex with men (MSM) and transgender women were recruited and syphilis prevalence was assessed on study entry and incidence was measured during the follow-up phase.

The initial prevalence of syphilis (Rapid Plasma Reagin test (RPR) positive) was about 14% and was similar in both the drug and placebo groups. Overall, syphilis incidence during the trial did not differ between the arms at 7.3 per 100 person-years (p=0.304) but HIV incidence did increase with incident syphilis with a HR of 2.6 (95% CI 1.6 to 4.4; p<0.001). This was greatest in the first 90 days after syphilis diagnosis than >90 days. Interestingly, no effect of PrEP was seen on syphilis incidence. In the current debate about when to use PrEP could a new syphilis diagnosis be a realistic indicator to help narrow down those most at risk?

Strategic Timing of AntiRetroviral Treatment (START)

As this goes to press comes news of the START study being halted early with the Drug Safety Monitoring Board favouring putting all participants on ART regardless of CD4 count.4 ,5 Interim results released show that there were just under half the number of AIDS defining and non-AIDS defining serious events or death in the on-treatment arm (41 vs 86), compared with the ‘standard of care’ arm (starting antiretroviral (ARVs) at CD4 <350 cells), a reduction of 53%, although overall absolute risks were small in both arms. This is robust evidence we have all been waiting for and further information is expected between writing this clinical round up and publication. But what are the implications for daily practice? For many who have already opted to treat at higher CD4 counts perhaps little will change. In the UK, we already have a good record of starting and maintaining patients on treatment. And what of the implications for onward transmission? Just as one question is answered (for now), new challenges appear.