What happens to people who become HIV positive in prevention trials?

One of the most contentious issues in HIV prevention trials has been the question of who is responsible for the care of people who become infected during the trial, and whether they are entitled to compensation. Two presentations at the Microbicides 2010 Conference investigated what actually happened to women who seroconverted during the two trials of the candidate microbicide PRO 2000.

Sharon Riddler of the University of Pittsburgh analysed what happened to women who had seroconverted (become HIV positive) during the HPTN 035 study , the smaller of the two trials.

There were 3087 women in this trial, of whom 139 (4.5%) seroconverted. One hundred of them are currently in an ongoing prospective cohort called MTN 015, which will analyse the care received by seroconverters not just in the HPTN 035 trial but also the CAPRISA and VOICE trials of tenofovir microbicides and pre-exposure prophylaxis.

The median age of the women was 27 at the time of enrolment into the cohort. Women joined the cohort, on average, 18 months after seroconversion, because it took time to set up the cohort: enrolment for women who seroconvert in CAPRISA and VOICE should be much faster. The average follow-up time so far is ten months.

There have been twelve AIDS-defining evens in ten participants, four of them severe. So far there has been one known death possibly related to HIV, of a woman who died of TB 22 months after seroconversion.

At the time of enrolment the median CD4 count of women not on treatment was 405 cells/mm³, and their average viral load 8000 copies/ml; the average CD4 count in women on treatment was 560 cells/mm³ and their viral load 400 copies/ml. Fifteen women not on antiretrovirals had a CD4 count under 250.

Only 50 women had ever registered for clinical care, and only 30 were taking antiretrovirals as treatment; 23 were taking d4T/3TC/nevirapine, which is still the cheapest and most frequently prescribed regimen in the four southern African countries in which the trial took place (there was also a site in Philadelphia in the USA).

Nine women had also taken antiretrovirals purely in order to prevent mother-to-child HIV transmission; in all but one case this consisted of AZT monotherapy (single-dose nevirapine was not counted as therapy).

The most striking finding from the study was that 40% of the women taking treatment stopped treatment altogether during the follow-up period, even though the average time between enrolment and taking treatment was only 13 months. Although side effects were mentioned, there was no detailed analysis of why women ceased therapy.

“Despite participation in a previous microbicide trial, many women were not accessing care for HIV infection,” Sharon Riddler commented.

Another study by Sharika Gappoo of the South African Medical Research Council looked at treatment rates amongst women who seroconverted at the Durban sites of the other PRO 2000 study, MDP 301.

Out of 2391 enrolled in the trial at Durban, 165 women (7%) seroconverted. Referral systems had been set up with local HIV clinics in advance of the trial. Sixty-one (37%) of the women, however, couldn’t be traced and were lost to follow-up. Of the remainder, three-quarters (47% of all seroconverters) eventually accessed care although, comment the researchers, “it took several counselling sessions and a lot of encouragement before they attended local clinics”.

Eleven other women joined others in being referred to SPARTAC (Short Pulse Anti Retroviral Therapy at HIV Seroconversion), a clinical trial to see if giving people three months or a year of therapy as soon as possible after infection enables them to delay taking long-term therapy.

Sixteen women who kept in touch with the researchers refused to access care. “Many did not take up referrals due to denial, stigma or other commitments (work, caring for children, etc.)” say the researchers.

Reasons quoted by the women included fear of disclosure to family, friends or people they knew who worked at the clinics; denial of their HIV status; concerns about drug side effects; economic considerations (having to work, the cost of travel to the clinic), preferring traditional medicine; and feeling well and not thinking it necessary to access care.

Pointing out that future microbicide trials will be of ARV-based formulations and have potential for resistance, the researchers say that future trials will need “a more stringent mechanism…to monitor and evaluate various factors that impede participants accessing HIV-related care”.