Pilot study finds weekend breaks from HAART may be possible on NNRTIs

An intriguing study presented on the second day of the Fifteenth International AIDS Conference examining the feasibility of intermittent therapy taken five days a week, with two consecutive days off, has found that it may indeed be an option for those taking non-nucleoside-based HAART, although the strategy appears much riskier for those on protease inhibitors. However the researchers emphasise that the results are preliminary and that the strategy should not be adopted without careful discussion between doctor and patient.

Investigators from the Community Research Initiative of New England sought to evaluate virologic control, CD4 counts, and patient preferences in 30 HIV-positive individuals with sustained viral suppression who changed from their standard daily antiretroviral schedule to a five day on/two day off treatment schedule. The study was called FOTO: Five days On, Two days Off. “This schedule,” they said, “was chosen to minimise the risk of viral escape with brief interruptions while maximising adherence by mimicking a typical five day work week, with a two day weekend....and also decreases antiretroviral exposure and cost by 28%.”

Twenty-four week data were available for 27 of the 30, 23 of whom were men, 19 of whom were Caucasian, and whose median age was 41 (range 28-58). All participants had plasma viral loads at time of study screening of less than 75 copies/ml for at least three months, with a baseline median viral load of less than 50 copies/ml (range 3 (range 221-1162). Ten were on efavirenz-based HAART, with either two (n = 8) or three (n = 2) additional nucleosides (NRTIs). Seven were on nevirapine-based HAART, with either two (n = 6) or three (n = 1) NRTIs.

Ten were on PI-based HAART, five of whom were taking Kaletra and saquinavir with no additional NRTIs, and three of whom added two NRTIs to this dual boosted PI regimen. The remaining two took nelfinavir plus two NRTIs and nelfinavir, saquinavir and nevirapine. NRTIs used included tenofovir, 3TC, abacavir, ddI and d4T. It should be noted that all the individuals entered the study whilst already taking therapy chosen by themselves and/or their physician.

Follow-up data ranged from 24 to 48 weeks. Of the ten in the efavirenz arm, all ten remained suppressed (

The PI-based arm, however, had two individuals with virological rebound by week 24 and a further study dropout due to substance abuse issues. However, the remaining seven were still fully suppressed at 48 weeks. One individual who experienced viral rebound was on Kaletra and saquinavir, and had prior treatment only with ddI and 3TC. His viral load at rebound was 3300 copies/ml, and ten days later was 526 copies/ml. Genotype resistance testing found a new PI mutation (36I – a naturally occurring mutation which facilitates 90M, a saquinavir-associated mutation) although phenotypic testing found no change in sensitivity to either of the PIs, and he subsequently resuppressed his viral load to below 50 copies/ml on daily therapy.

The second individual had multi-drug resistant HIV prior to starting his current therapy of Kaletra, saquinavir, ddI and abacavir. At weeks 16 and 18, he experienced ‘blips’ of 116 and 202 copies/ml but resuppressed on continuous HAART. He returned to the FOTO schedule for three weeks but at week 24 experienced a rebound to 1300 copies/ml. One new mutation, 214L, a thymidine analogue mutation (TAM) weakly associated with ddI and abacavir resistance, was found by genotypic resistance testing. He also subsequently resuppressed his viral load to below 50 copies/ml on daily therapy.

Six individuals on Kaletra and saquinavir had drug levels tested and five of the six were found to have sub-therapeutic levels of lopinavir and four of the six sub-therapeutic levels of saquinavir at the end of the second day off therapy, which suggests that the FOTO strategy is much riskier for those on PIs, even when boosted with low-dose ritonavir.

Adherence was self-reported to be 100% and a quality of life survey reported a very strong preference for the FOTO schedule compared with continuous daily therapy. No serious drug-related adverse events were reported, although there were some side-effects experienced on restarting HAART after the two day break. Four individuals on efavirenz reported vivid dreaming, fatigue, insomnia or headache; one on nevirapine reported nausea; and four on any PI reported diarrhoea or fatigue. No significant differences were seen in any fasting lipid measurements at baseline, and weeks 24 and 48.

Since this was only a small study, the implications of virological rebound seen in people only on PI-therapy must be interpreted with caution. However, it appears that the five day on, two day off strategy was successful for all of the participants taking NNRTI-based HAART for at least 24 weeks, and with a strong patient preference for this strategy, this novel intermittent therapy option warrants further investigation.