A universal test-and-treat policy may sound like a solid route towards reducing the number of new HIV infections, but results of a major five-year trial in South Africa show that, in isolation, it is not. A Daily Maverick report says that according to the study, although home screening proved popular, stigma and other factors still prevent patients from seeking out treatment – even if it is offered freely and immediately.
The research offered repeat home testing and immediate antiretroviral (ARV) treatment in trial clinics for those who tested positive. It showed that while there was significant take-up of the offer to screen for HIV at home, few of those diagnosed with HIV sought treatment. Their entry into the healthcare system, the researchers said in a statement, was “infrequent and slow”. Furthermore, HIV transmission in the population was not reduced.
The report says the research, known as the Treatment as Prevention (TasP) trial, was run by the Africa Health Research Institute (AHRI) and the French Agency for Research on Aids and Viral Hepatitis (ANRS) in the Hlabisa Area, northern KwaZulu-Natal, from March 2012.
The findings are significant as this is the first of four international randomised trials to assess the effectiveness of the universal test-and-treat strategy in reducing HIV transmission. It is also the first to report its results. “The results are crucial for governments to consider as they implement or scale up their ‘treat all’ programmes,” the AHRI said.
In 2016, South Africa had an estimated 7.1m people living with HIV. One-third of all new infections in the sub-Saharan region in 2016 were in South Africa. South Africa also has the largest ART programme in the world, and spends over R20bn on its HIV/Aids programmes annually.
AHRI director, Professor Deenan Pillay, co-led the study and he is quoted as saying that the results pointed to four main areas that needed work. First, a mixture of stigma and patient discomfort in public health clinics, possibly due to long travel and waiting times. Second, people were possibly more mobile or travelling for work, which could take them away from their home clinics. “That’s an impediment to expecting people to turn up at regular intervals,” he said. “There must be things we can do to help people access care seamlessly if they are travelling.”
Third, he argued, there was a difference in how different genders experienced treatment. The healthcare sector was “pretty feminised”, he said, which might lead to a feeling of shame in male patients if they were accessing care from female healthcare workers. And fourth, it could be helpful not to identify people visiting clinics in HIV-specific queues. “Generalising chronic care would be a big plus,” he said in the report.
Previous research, including research by the AHRI in rural KZN populations, has demonstrated that roll-out of ARV treatment (ART) has significantly reduced death, the AHRI said. “Several other studies done in this population and elsewhere have shown that ART also has the capacity to reduce transmission to other people.” It is therefore crucial for policy-makers and fieldworkers to help patients bridge the gap between diagnosis and accessing treatment.
“Despite being a negative finding, this is a very important finding in terms of HIV policy,” said Pillay. “AHRI has previously demonstrated the potential benefit of ‘treat all’, but this trial has now shown that implementing the policy is not enough. Our next steps are to investigate if initiating treatment at home might increase people’s entry into care. We are also looking at potential solutions including financial incentives and mobile and technology options, some of which could be gender specific.”
The report says to perform the research, the trial area was divided into 22 geographic zones or clusters, each of about 1,280 people or older. These were randomly split into two equal groups, an intervention group and a control group. Over 13,000 people were included in the intervention groups altogether, and just shy of 15,000 in the control groups. Every six months, the participants were offered rapid HIV screening in their homes.
In the intervention group, people who tested HIV positive were offered immediate ART, whatever their CD4 count. In the control group, treatment was initiated according to the previous indications recommended by South Africa’s Department of Health (originally a CD4 count of less than 350, and from January 2015 a CD4 count of less than 500). Mobile treatment clinics were sent to each area to facilitate access to care for people who tested positive. They could also use local health services at any time.
According to the researchers, screening at home was well accepted, and HIV status was identified at least once for 88% of the people contacted.
However, there was no significant population-level impact of universal ART on the HIV infection rate. The annual incidence of HIV infection was an estimated 2.13% – meaning 2.13 individuals out of 100 were infected in a given year – in the intervention group, versus 2.27% in the control group. These figures, said the authors, were not statistically significant.
“Linkage to HIV was both slow and poor, leading to a lower than anticipated increase of population ART coverage,” AHRI said. “The rate of linkage-to-care was similar in both arms, with only 30% of individuals registering at the trial clinic within six months of home HIV diagnosis, considerably lower than the expected 70%.”
Unfortunately, Pillay is quoted as saying, improving the linkage between testing and treatment – or encouraging patients to access care – could potentially prove difficult. “South Africa has the biggest treatment programme in the world,” he pointed out. “However, only 50% of the people who need treatment are on treatment, so it is a matter of doubling that number. That is if the rate of infections stays static, but there are new infections.
“It is almost impossible for the current structure of the Department of Health to deal with a doubling of numbers. So there must be different ways in which treatment is given, which could be cost neutral.” This could include arranging for patients to pick up medications in their home communities rather than travelling to clinics, or introducing novel ways to monitor infections, at home, in mobile clinics, or in community centres.
“There are ways of decentralising care,” Pillay said. In his view, the study highlights the need to make it easier for patients to seek care without facing stigma, or to be able to adhere when access to their home clinic is difficult for whatever reason.
The authors estimated that only four out of 10 HIV positive people living in the region had an undetectable viral load. Yet UNAIDS estimates that to meet its targets aligned to ending the epidemic by 2030, seven out of 10 HIV positive people must have an undetectable viral load by 2020.
However, despite the lack of impact on transmission at population level, the trial did further underline the individual benefits of universal ART. Evidence included high viral suppression observed at 12 months, the researchers said. “There was a higher retention rate in the intervention than the control arm, with participants on ART more likely to be retained in care than those pre-ART. These are strong arguments to roll out universal test and treat without any restriction,” they argued.
“Despite the offer of treatment after an HIV positive diagnosis, there was clearly a reluctance on the part of many to be treated immediately,” AHRI said. Besides the stigma factor outlined by the study authors, other reasons have been cited elsewhere, from discrimination by medical staff to lack of transport, distance from facilities, illegal and unscrupulous dealers, a preference for alternative treatments and having access, but experiencing social difficulties with adherence.
Pillay said he was “amazed” that there could still be so much reluctance to seek treatment – and so much stigma – in an area such as KZN, where 30% of the population is infected, “so every family will have a member with HIV, or know somebody who is infected”.
“Yet,” he said, “in that circumstance, stigma still exists.” The practical solutions, he believes, include continuing to treat HIV/Aids as a chronic disease, but rolling this into care for other diseases such as hypertension and diabetes, or linking it to contraception. “This would provide an environment where people are not just being seen as having HIV.”
Further, he said in the report, a strong education component that began at school was crucial, but this was a concern where the public education service was facing its own challenges.
Pillay said the trial had shown that “treating ourselves out of the epidemic” or, to phrase it differently, eliminating the disease with straightforward treatment only, was “a really difficult thing to do”. HIV/Aids would not be eradicated with treatment alone, he said – it would require a more aggressive focus on prevention, as well as making it easier for patients who are on treatment to adhere to treatment programmes.
ANRS director, Professor François Dabis, who co-led the study, added: “We should not be distracted to promote the universal test-and-treat strategy, and look for more efficient solutions to reach this goal of test-and-treat all as quickly as possible.”
Background: Universal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa.
Methods: We did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and <500 cells per μL from January, 2015; control). Participants and investigators were not masked to treatment allocation. We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up. This study is registered with ClinicalTrials.gov, number NCT01509508, and the South African National Clinical Trials Register, number DOH-27-0512-3974.
Findings: Between March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84–2·39) in the intervention group and 2·27 per 100 person-years (2·00–2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87–1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83).
Interpretation: The absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence.
Collins C Iwuji, Joanna Orne-Gliemann, Joseph Larmarange, Eric Balestre, Rodolphe Thiebaut, Frank Tanser, Nonhlanhla Okesola, Thembisa Makowa, Jaco Dreyer, Kobus Herbst, Nuala McGrath, Till Bärnighausen, Sylvie Boyer, Tulio De Oliveira, Claire Rekacewicz, Brigitte Bazin, Marie-Louise Newell, Deenan Pillay, François Dabis