ANRS12249 is one of
several randomised trials designed to answer this question. Frank Tanser, who conducted the
original surveillance study that first noted the link between treatment and
incidence in KwaZulu Natal, described it and the other huge treatment-as-prevention comparison
studies that are underway in southern and eastern Africa.
ANRS12249 is taking place in an area of KwaZulu Natal near that covered by the previous surveillance study. The
entire population will be offered home-based HIV testing and those testing positive in intervention communities will
be offered referral to care and immediate ART (in control communities, they will be offered treatment according to South African treatment guidelines). There are 90,000 people in the
original surveillance area and 22,000 in the new intervention area – which, as
we will see, is small compared to some other treatment as prevention studies.
Data
were presented at the International AIDS Conference at Melbourne earlier
this year by principal investigator François Dabis, who noted that while home
testing appeared to be very acceptable, people were taking longer than anticipated to come
forward for treatment if they did test positive.
Tanser said, however, that
already some benefits were being seen to the treat-everyone approach. In the
intervention areas, 77% of everyone with HIV was diagnosed, of whom 73% were in
care, of whom 80% were on ART, meaning 45% of everyone with HIV was on ART. Tanser
said that an estimated 31% more people were in care and 28% more were on treatment
than would be the case if treatment was being offered according to South
African national guidelines.
Between now and 2019, four other
huge treatment-as-prevention trials, each slightly different, and involving up
to two million people, will test whether intensified treatment really can bring
down HIV infections on a population level.
The POPArt trial is the biggest of these, involving no fewer than 1.2 million people. The POPArt intervention includes home-based HIV testing by community health providers, an offer of ART upon HIV diagnosis at any CD4 count, voluntary medical male circumcision, the prevention of mother-to-child transmission, condom provision and tuberculosis (TB) monitoring and treatment. Communities are randomised into
three arms: one receiving the full POPArt intervention; one receiving the POPArt prevention package but ART according to country guidelines (currently at below 500 CD4 cells/mm3 in Zambia and below 350 cells/mm3 in South Africa, though this is soon to rise to 500); and one receiving the standard of care in their country. The estimated
completion date is 2018. As estimating HIV incidence for a trial this size
would be expensive, a subset of around 50,000 people will be tested frequently for
incident HIV infections.
The Botswana Combination
Prevention Programme (BCPP) is
studying 180,000 people in 30 villages in Botswana. It will randomise 15
villages to standard of care and 15 to a package similar to the POPArt one plus
ART for everyone with a viral load above 10,000 copies/ml. It should report by
late 2017.
The SEARCH trial is taking place in Kenya and Uganda, and is in some
ways the most ambitious as it will also measure the effect of intensified
treatment on a number of socioeconomic indicators and health outcomes not directly
related to HIV. It will randomise 320,000 people in 32 communities to receive
either standard of care or ART at any CD4 count, intensified linkage to and
retention in care for people with HIV and frequent testing for high-risk individuals. Interestingly, it will also provide a multi-disease prevention campaign, testing people for
malaria, hypertension (high blood pressure) and diabetes. It was fully
enrolled this July and 89% of participants have had an HIV test.
SEARCH will evaluate the
programme not just for HIV incidence but for additional gains: maternal and
child health, TB, education level, earning power and costs. The reason for
testing people for hypertension and diabetes is to see if such an intervention could be
of benefit in low-income areas where these are the most urgent health problems.
SEARCH will report in 2019.
The final study, MaxART, is a three-year
implementation study led by the Swaziland Ministry of Health and supported by a
number of partners including the Clinton Foundation. It will not measure
incidence directly; its aim is to study the feasibility, acceptability,
scalability, and clinical outcomes,
including AIDS, of a national roll-out of ART for all in this small but
high-prevalence country.
Fourteen clinics in one region are included in the
study implementation. Health facilities transit, two at a time, from the
control (standard of care) to the intervention (ART for all HIV-positive
clients) stage. The order in which the facility groups transition is randomized,
with the health workers and study participants blinded to the timing so as to
minimize bias. Community participation and a robust communications strategy are
also an integral part of the study implementation to ensure that the community’s
interests are heard and protected.