The global scale of antiretroviral therapy (ART) has resulted in the transformation of HIV infection as an inevitably fatal disease transformed into a chronic disease, although incurable; an infection that requires lifelong treatment with the technology we have at the beginning of the 21st Century.
An increasing number of children infected through mother-to-child transmission of HIV, vertical transmission, which Cuba was the first nation to eradicate, who died in childhood in the pre-ART period, are now reaching adolescence and about to facing the prospect of having to take ART daily with better adherence for the rest of their lives2,, 3, 4
Em Lancet HIV, the PENTA 16 study shows the findings of the BREATHER study group report, an open-label study comparing daily and continuous ART shots with short-cycle treatments allowing 2 untreated days each week.
One hundred and ninety-nine participants aged 8 and 24 years who had suppressed viral load for at least twelve months prior to enrollment and were taking a ART regimen containing a long-term treatment with efavirenz were recruited from 11 countries all around the world. At 48 weeks, six (6%) of 99 children in the short-course treatment group versus seven (7%) of 100 in the continuous treatment group had virological rebound (HIV viral load> 50 copies per ml; difference -1 2%, 90% IC - 7, 3 to 4, 9), showing that short cycle treatment is not inferior to continuous treatment.
There was no statistical difference between the groups in the proportion of participants who developed large resistance mutations or in the proportion of adverse events. This is the first study to show that controlled discontinuation seems to be safe both in terms of maintaining viral suppression and in the emergence of drug resistance. In particular, the study was done in locations of geographic configurations of various configurations achieving an impressive retention rate with only one participant lost in any follow-up.
Children have an expectation of taking ART for an average of about 20 years longer than adults and strategies that allow time out of HAART could be an effective way to reduce organic fatigue by treatment.6
In addition, reducing the use of ART through a short course of treatment can provide potential cost savings. The short cycle treatment strategy was highly acceptable for the
participants, especially since it allowed them to socialize on the weekends, which is contrary to the main barrier to taking the medications. Even patients who are virologically suppressed reporting intermittent use with a short drug-free period and short cycle treatment provides a regulated time without medication and a legitimate way of losing doses.7
The concern is that such a strategy can give the message that the missed shots are acceptable and that they could not affect the viral load (translator's remark: In conversation with a nurse in married AIDS the standard target is 90% you could miss a simple take in the month). Adequate counseling is therefore essential to ensure that the results are not misinterpreted and that patients understand that there is a maximum threshold of disruption in the specific phase treatment for 2 days a week.
Namely, the findings of the present study are usable only for stable and well established patients on HAART.
The mean time to ART before the randomization of this study was 6 years in children had had viral load suppressed for at least twelve months. In addition, the results can not be extrapolated for children who have failed prior treatment or with ART containing reduced doses of Efavirenz (equivalent to 400 mg for adults) or even for other long-acting ART regimens. The follow-up period was short and a two-year extension of the study was planned that will provide data for the long-term sustainability of this short-cycle treatment strategy. Other questions to be answered before short cycle treatment may become a viable option.
The study was conducted under strictly controlled conditions with intense viral load monitoring. Research is needed to understand whether the study could be safely implemented in resource-limited settings where routine monitoring of viral load is unavailable or infrequent.
Further investigations could also assess whether the short cycle treatment with the new long acting drugs and make available that have a greater barrier to resistance and if they are more tolerable, such as tenofovir and dolutegravir alafenamide.8
Viral suppression is the ultimate goal of improving health outcomes and reducing HIV transmission, thereby conferring the benefits to individual and public health.9, 10
A good adhesion to HAART is crucial to ensure sustained virologic suppression. Adherence to chronic disease treatment falls during adolescence and unfortunately HIV is no exception.11 Adolescents face several barriers to adherence and our experience is that no intervention will be sufficient to ensure the high levels of adherence required to maintain virologic suppression.12 Therefore, we need several different approaches in our arsenals to support adherence in this age group.
We now have a promising new innovative approach that could be offered to young people facing the prospect of learning ART.
I declare there are no competing interests.
Rashida A Ferrand
- A UNAIDS. How AIDS has Changed Everything-ODM6: Fifteen Years, 15 Lessons from AIDS Hope Answers. UNAIDS, Geneva; 2015
- Newell, ML, Coovadia, H, Cortina-Borja, M, Rollins, N, Gaillard, P and Dabis, F. mortality of infected and uninfected infants born to HIV-infected mothers in Africa: an analysis pool. The Lancet.2004; 364Finished
- | PubMed
- Hazra, R, Siberry, GK and Mofenson LM. Growing with HIV: children, adolescents and young adults with acquired HIV infection in the perinatal period. Annu Rev Med. 2010; 61Finished
- | PubMed
- Foster, C, Judd, UMA, Tookey, P et al. Young people in the UK and Ireland with HIV acquired in the perinatal period: the legacy of services for pediatric adults. AIDS Patient Care STDS. 2009; 23: 159-166
- | PubMed
- Week-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (Respite): lota, open, non-inferiority, phase 2 / 3 trial. Lancet HIV.2016; (published online June 20.)http://dx.doi.org/10.1016/S2352-3018(16)30054-6.
- Lowenthal, ED, Bakeera-Kitaka, S, Marukutira, T, Chapman, J, Goldrath, K, and Ferrand, RA, acquired perinatal HIV infection in sub-Saharan African adolescents: A review of emerging challenges. The Lancet infect Dis. 2014; 14Finished
- Bernays S, Seeley J, Paparini S, Rodes T. 'I'm afraid of getting stuck in my lie': challenges for self-reported adherence to young people living with HIV. AIDS Impact; Amsterdam, The Netherlands; July 28-31, 2015.
- Elliot, E, Amara, Jackson, et al. Elvitegravir Dolutegravir and plasma concentrations after cessation of drug ingestion. J Antimicrob Chemother. 2016; 71Finished
- Attia, S, Egger, M, Muller, M, Zwahlen, M and Low, N. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS. 2009; 23Finished
- | PubMed
- Mills, EJ, Bakanda, C, Birungi, J et al. Life expectancy of people receiving combination antiretroviral therapy in low-income countries: analysis of a Uganda cohort. Ann Intern Med. 2011;155Finished
- | PubMed
- Nachega, JB, Hislop, M, Nguyen, H et al. Antiretroviral therapy adherence, virological and immunological results in adolescents compared to adults in southern Africa. J Immune Defic Syndr will acquire Aõâ. 2009; 51Finished
- | PubMed