TREATMENT OF SERO-DISCORDANT COUPLES: IMPLICATIONS FOR YOUNG PEOPLE JJ KUMWENDA (FRCP-UK)

SYNOPSIS OF HPTN 052 A randomized clinical trial to evaluate the effectiveness of Antiretroviral Therapy plus HIV primary care versus HIV primary care alone to prevent the sexual transmission of HIV-1 in sero-discordant couples.

STUDY OBJECTIVES Primary objective: To compare the rate of HIV infection among partners of HIV infected participants in two study arms – ARM 1: Antiretroviral therapy plus HIV primary care at time of enrolment – ARM 2: HIV primary care alone until the participant has two consecutive measurements of CD4 cell count below 250 cells/mm3 or develops an AIDS defining illness.

STUDY OBJECTIVES Evaluate the optimal time to begin antiretroviral therapy in order to reduce illness and death among people infected with HIV/AIDS.

Secondary objectives Determine long term safety of ART Characterize the pattern and rates of ART drug resistance Assess factors associated with adherence to therapy Evaluate effectiveness of couples counselling and characterize patterns of sexual behaviour in couples in both arms

Study design Phase 3, two arms, randomized controlled multicenter clinical trial Study population: HIV-1 sero-discordant couples in which the HIV infected partner is ART naive and has CD4 cell between 350 and 550 cells/mm3 Sample size: 1750 sero-discordant couples Study arms: two arms, assigned 1:1 ratio. – ARM 1: ART at enrolment plus HIV primary care – ARM 2: HIV primary care alone until participant’s CD4 cell count falls below 250 on two consecutive times or develops an AIDS defining illness

PARTICIPATING SITES Botswana: Gaborone Brazil: 2 sites Porto Alegre and Rio de Janeiro India: Chennai and PUNE Kenya: Kisumu Malawi: Blantyre and Lilongwe South Africa: Johannesburg and Soweto Thailand: Chiang Mai USA: Massachusetts Boston Zimbabwe: Harare

Results 1763 couples were enrolled from April 2005 to May % were heterosexual Mean age was 33 years Mean CD4 cell count at entry 436 cells/mm3 ( )

DSMB FINDINGS IN RELATION TO HIV TRANSMISSION 39 cases of HIV transmission among previously uninfected partners 28 transmissions were linked (i.e. The virus found in the infected partner did come from the index case) 11 transmissions were not linked (virus found in the infected partner came from someone other than the partner registered in the study) or were still being analysed 27 transmissions in the delayed arm versus 1 in the immediate arm Over 96% reduction in HIV transmission in the immediate arm HIV incidence as a whole in the study was lower than what was expected

DSMB TRANSMISSION IN RELATION TO BENEFITS OF STARTING ART EARLY 105 cases of ill health in total 65 cases in delayed arm versus 40 in immediate arm 17 cases of extrapulmonary TB in delayed arm compared to 3 in immediate arm Deaths were 10 in immediate arm versus 13 in delayed arm

ISSUES WHEN CONDUCTING 052 Difficult to enrol young people (most go for HIV testing as couples but break up immediately if results are sero-discordant Difficult to keep sero-discordant couples together. Required constant counselling Keeping to schedule of events was a huge task

ISSUES RELATED TO YOUNG PEOPLE HIV incidence highest in the age group especially in women 4.9% HIV prevalence in year age group in Malawi more in girls 6.8% compared to 3.1% in boys Trans-generational sex seems an important risk factor in girls Only 42% Overall Knowledge in the adolescent age group about HIV prevention

What to with 052 results Malawi to follow WHO recommendation to increase CD4 cell count threshold to 350 for initiating ART Preparation underway to do district-wide door to door testing for couples. Uptake for HIV testing improves significantly on home testing Increasing treatment threshold to 550 as was in 052 has both policy and resource implications Governments normally follow WHO lead.