Three presentations at the recent 7th International AIDS Society conference on HIV Pathogenesis, Treatment and Prevention from different parts of Africa looked in turn at the potential impact on the HIV epidemic of earlier antiretroviral therapy (ART); institutional factors that may prevent people accessing it early; and individual feelings about ART that may also make people hesitant to start it.
Ivory Coast: the benefits of ART
From the Ivory Coast, a study found that giving antiretroviral treatment to people early would reduce the likelihood that they would infect their partners by 90%, without any increase in potentially risky sexual behaviour.
The Temprano study was run by the French AIDS research institute ANRS and randomised 957 people with HIV in Abidjan, Ivory Coast, either to immediate treatment or to treatment when people's CD4 count fell below what was then the World Health Organization's threshold for treatment initiation of 200 cells/mm3. The trial took place between January 2009 and September 2011 and halfway through, in early 2010, the WHO revised its treatment threshold upward to 350 cells/ mm3. The study changed its threshold accordingly (at the IAS 2013 conference another revision upward to 500 cells/ mm3 was announced).
The trial had the unusual feature that its participants were largely female: 80.5% were women. Twelve months after enrolment, participants were asked to fill out a behavioural questionnaire and the researchers compared behavioural characteristics and viral load in early versus guideline-treated participants.
They found very little difference in sexual behaviour between the immediate-treatment versus guideline-treated group. Forty-six per cent of participants overall had had sex in the past month and 23% had had casual sex. There was no significant difference in the proportion of people reporting potentially risky sex: 10% of the early-treated versus 12.8% of the guideline-treated, a non-significant difference (p=0.17).
Whether the sex had actually posed a risk depended, amongst other things, on whether participants were virally suppressed. Whereas only 17.1% of those in the early-treated arm had a viral load over 300 copies/ml, 89.5% of those in the guideline-treated arm did. Assuming that people with viral loads under 300 copies/ml are uninfectious, the researchers calculated that only 2.4% of early-treated participants, or only about 11 or 12 individuals, were exposing their partners to potential HIV infection, compared with 11%, or over 100 individuals, in the guideline-treated arm.
This implies a protective value of early antiretroviral treatment, in a trial that was designed to measure risk behaviour rather than ART efficacy, of about 90%.
Kenya/Uganda: obstacles in accessing ART
The earlier people access ART, the more effect it has in preventing HIV. But what are the barriers to early access? Data from a study of pre-exposure prophylaxis (PrEP) provided interesting data on how soon people actually start ART once they become eligible, and on the reasons for delayed access.
Partners PrEP randomised the HIV-negative partner in 4247 HIV-serodiscordant couples in Kenya and Uganda, where the HIV-positive partner had a CD4 count above the WHO guidelines threshold and was not on ART, either to receive PrEP or placebo. It found PrEP to be 65% protective.
If the HIV-positive partner's CD4 count fell below the guideline threshold, they were immediately counselled to start ART and were referred to a local HIV centre (the trial protocol did not allow for the prescription of ART as treatment by the researchers themselves). The data reported come from 2008 to 2011 and again, the treatment threshold was raised in 2010 in line with the WHO guidelines revision.
The HIV-positive partner became treatment-eligible in 2178 of the couples (51%) and was referred. Of these, 180 (8%) were lost to follow-up, 1998 attended for a follow-up visit at least once, and 1427 (71%) of these started ART during the three-year trial. While there was delay in accessing HIV – only 50% had started it within six months of referral – most eventually started, with 90% of those who were followed up for two years or more starting ART. As presenter Andrew Mujugira showed, this access rate compared quite favourably to the rates seen in a number of different cohort studies in the US.
However, only 66% of those referred with a CD4 count below the AIDS-defining limit of 200 cells/mm3, who were in danger of serious illness, began ART within six months of referral, a proportion no higher than among those with CD4 counts between 200 and 350 cells/mm3.
Self-reported barriers to accessing ART included protocols that mandated adherence counselling before starting people on ART. One-third of HIV centres expected participants to attend three adherence-counselling appointments before starting ART: these might only be monthly, so starting ART could be delayed by three months, and the average delay between attending the first HIV centre appointment and starting ART was 49 days in those receiving adherence counselling versus 14 days in those not receiving it. There was no difference in adherence or in the proportion achieving undetectable viral load between those who received adherence counselling and those who did not.
Another institutional barrier was that HIV centres insisted on re-doing the participants' CD4 counts rather than accepting the referrers' result. As a result of this constraint 21% of referred participants were refused ART because their CD4 count at the HIV centre was actually somewhat above the ART threshold. This may reflect short-term natural variations in CD4 count or different laboratory methods, but counts are unlikely to start increasing over the long term in people not taking ART, so this is likely to delay ART unnecessarily for those close to the treatment threshold.
Botswana: attitudes towards taking ART
Partners PrEP study participants were probably unusually well motivated to take ART both as members of a jointly enrolled couple and because they already had experience of their partner taking PrEP (or placebo). This may not be the case in typical clinical settings. To explore some attitudes towards taking ART in depth, a smaller study from Botswana conducted semi-structured interviews and two focus groups with twelve people with HIV (nine women and three men) from the same town, Mochudi. All participants had CD4 counts over 350 cells/mm3 and viral loads over 50,000 copies/ml – so they were not yet clinically eligible for ART but might be interested in its prevention benefits.
The interviews reinforced how important HIV stigma remains in Botswana, despite or perhaps because of HIV's high prevalence. Participants were well aware of the clinical benefits of ART but also cited being no longer being visibly unwell as a good reason to take ART. Conversely, some were worried about being stigmatised because if people saw they were taking ART they would know they had HIV.
Instances of HIV stigma were commonly reported by the group: one women said “There was one at our work, and it was known she had this disease. Then I saw people scorned her... the others no longer used the toilets that she used.”
Against that, a number of participants had internalised the perception that, these days, “it is a disease like anything else. It is the same as being sick with diabetes.”
There were concerns about side-effects, about the time and expense of going to the HIV clinic and accessing ART, and again about disclosure and stigma: people were worried that the HIV clinic was sited in the same hospital that everyone went to. People also felt they were not capable of the lifelong commitment to ART: one said “It is very difficult, I don't know if I will get used to it or forget them”.
Another previously unexplored theme that arose in the discussions was a perceived link between ART and drinking alcohol. The two were seen as incompatible, either for reasons of interaction or because people were sure that drinking was incompatible with adherence and would lead to treatment failure. Taking ART was equated with sobriety, so people who drank were not ready for it: “My partner takes [the pills] but he doesn't take them well, because he is a drunkard”, one woman said. “He will be out and the time will come for him to take them and he doesn't.”
Against these barriers to ART, people cited experiences of friends recovering from AIDS as the best facilitator for taking ART, and in particular the fact that they can return to work: “You will see that a person will not now be sick day after day, and they walk, they work, and they were a patient who was just sleeping in blankets,” said a 61-year-old man.
The prevention benefits of ART were also stressed and was also seen as something that might help reduce stigma. “People should stop being ashamed, they should stand on their feet and fight this disease so that it finishes,” said one woman. “We should take these [antivirals] so that the virus will reduce, and its spread.”
Jean K et al. Early antiretroviral therapy, sexual behaviours and HIV-1 transmission risk: estimates from the Temprano-ANRS 12136 Randomized Controlled Trial, Abidjan, Côte d´Ivoire. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract MOAC0201, 2013.
Mujugira A et al. Delay in antiretroviral therapy initiation is common among east African HIV-1-infected individuals in serodiscordant partnerships. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract MOAC0202, 2013.
Logan A et al. Acceptability of early initiation of antiretrovirals for treatment as prevention among HIV-infected persons in Mochudi, Botswana. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract MOAC0204, 2013.