Flares of genital ulcer disease common in women starting HIV treatment, could temporarily increase infectiousness

Genital ulcers frequently flare-up in women starting HIV treatment, a Kenyan study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes suggests. A low CD4 cell count when HIV treatment was started and a history of genitals ulcers were risk factors for these short-term episodes of genital disease.

“Because genital ulcerative disease flares during the early period after antiretroviral therapy initiation could increase HIV infectivity, pre-treatment counselling include information about ways to reduce the risk of HIV transmission to sexual partners”, comment the investigators.

Genital ulcers are common in women with HIV. Sexually transmitted infections, especially herpes simplex virus-2 are frequently the cause. As such ulcers can cause both damage to the mucus membrane and inflammation, they may increase HIV viral load in the genital compartment, therefore meaning that there could be a greater risk of HIV transmission to sexual partners.

Soon after starting HIV treatment, some patients experience immune reconstitution illnesses. These can involve a temporary worsening of pre-existing conditions, including genital ulcer disease.

To obtain a better understanding of the frequency and timing of genital ulcer disease in women starting HIV treatment, investigators designed a prospective study involving 134 women starting HIV treatment for the first time. The study lasted six months. At baseline and regular intervals after initiating antiretroviral therapy, the women were questioned about the presence of genital ulcers and had a physical examination.

The median CD4 cell count when HIV treatment was started was 127 cells/mm³, and 82 women (62%) reported a history of genital ulcers at some point before starting HIV treatment.

After starting HIV treatment, genital ulcers were reported or observed in 54 women (40%) at 85 study visits (10%). The ulcers were detected by patient report only in 47% of cases, by physical examination in 38% of cases, and by both in 18%.

At baseline, the prevalence of genital ulcer disease was 10%. This increased to 17% after one month of HIV treatment, but fell to 6% after six months of antiretroviral therapy.

In the first set of statistical analysis, a baseline CD4 cell count below 100 cells/mm³, an AIDS diagnosis, and a history of genital ulcers were all significantly associated with a flare-up of genital ulcers during follow-up.

Subsequent analysis that controlled for potentially confounding factors showed that a history of genital ulcers remained highly significant (odds ratio [OR], 3.8; 95% CI: 1.9-7.7, p < 0.001), but a low baseline CD4 cell count was of only borderline significance (OR, 1.8; 95% CI: 1.0-3.4, p = 0.06).

Next the investigators restricted their analysis to cases of ulcerative disease which were diagnosed by physical examination. One month after starting HIV treatment, there was a 40% increase in the prevalence of genital ulcers from baseline in this subset of women, but this had fallen to 20% by month two, and after three moths of HIV treatment, was below baseline levels. Both a baseline CD4 cell count below 100 cells/mm³ and a previous history of genital ulcers were highly significant predictors (both P < 0.001) of flares in genital ulcer disease after starting anti-HIV drugs.

“We found that genital ulcer disease prevalence was relatively high at baseline (almost 10%), increased almost 2-fold in the first month, then returned to baseline thereafter”, write the investigators.

They therefore conclude, “although all women initiating antiretroviral therapy should be counselled about strategies for reducing their risk of transmitting HIV to sex partners, the data presented here suggest that women with a history of genital ulcer disease may benefit from additional risk reduction counselling regarding the potential for increased transmission risk in the first 1-2 months of therapy.”