Protease inhibitor monotherapy in clinical practice: valid option for undetectable patients

Patients prescribed protease inhibitor-ritonavir (PI/r) monotherapy in ‘real-world’ clinical practice achieve viral suppression rates equivalent to those seen in randomised controlled trials, according to two surveys presented to the second BHIVA/BASHH joint conference in Manchester.

Although at 80 at 85% rates of viral suppression did not match the best seen in triple therapy in naive patients, many patients who failed virologically became resuppressed if NRTIs or other drugs were reintroduced.

However, in one of the two studies, all but one of a small subgroup of patients who started monotherapy with a detectable HIV viral load failed to suppress the virus, underlining findings from randomised controlled trials (RCTs) that this strategy should only be considered for patients who have undetectable viral loads when placed on PI/r monotherapy.

The first survey (Simpkin) was a retrospective case note review of 68 patients at the Brighton HIV clinic. All but two patients had an HIV viral load under 40 copies/ml when placed on monotherapy, one had a viral load ‘blip’ (meaning a single viral load measurement over 40 but under 500 copies/ml) while the other had persistent low-level viraemia (last viral load = 66 copies/ml).

The main reason patients were placed on monotherapy was toxicity (37 patients) or the risk of it (19 patients). Another 18 were switched for adherence/simplification reasons.

Common reasons for switching were because patients had high cardiovascular disease risk and were taking abacavir (19 patients) and/or had chronic renal impairment (15 patients) or a history of it (seven patients – these categories could overlap). Three more patients had acute renal failure. Other reasons for PI monotherapy were lipoatrophy or its risk, liver problems or the risk of them, diarrhoea, peripheral neuropathy, osteopenia and central nervous system toxicity.

This was an ageing and treatment-experienced group with an average age of 52 (range, 30 to 79) and 13 years living with HIV. Half of them were taking boosted protease-inhibitor-plus-NRTIs triple therapy at the time of switching to monotherapy while twelve made a complete switch from an NNRTI-based regimen and 21 were taking more exotic combinations such as NRTI-sparing regimens, double boosted PIs, or quadruple NRTIs.

At the start of PI/r monotherapy 50% of the 68 patients were placed on darunavir and 43% on lopinavir with a handful on atazanavir or fosamprenavir. By the time of analysis, after a median time of one year on monotherapy, 74% of patients were on darunavir (6.5% had started taking it twice daily), 21% on lopinavir and 5% on atazanavir.

Fifty patients (74%) had a viral load under 40 throughout, while another seven (10%) had a single ‘blip’ over 40 copies/ml but resuppressed, and another, after a period of repeated blips, had had a viral load under 40 copies/ml for ten months. This means that ten patients (15%) failed monotherapy.

Four of these, however, were able to resuppress their HIV by adding back NRTIs, meaning that at the time of analysis 91% of patients had an undetectable viral load. Of the other six, two stopped therapy and one died, two have viral loads just over 40 copies/ml and are expected to resuppress, while one has a viral load of 259. This patient had documented adherence problems and was unwilling to take an intensified regimen.

In the second study, a prospective one from the Chelsea and Westminster Hospital in London (Brown), a very similar group of patients (average age 47, average time on antiretrovirals 12 years) were all switched to boosted darunavir (DRV/r) monotherapy from other regimens containing PIs. A third were on tenofovir/FTC, 11% on abacavir/3TC, another third on other combination therapies and 22% were already on PI/r monotherapy, mainly lopinavir/r.

Seventy-three patients switched while they had a viral load below 50 copies/ml and of these 86% were still below 50 copies/ml by week 48. Ten patients stopped taking monotherapy and three failed virologically, all three of whom had adherence problems.

It was a very different picture with the eight patients who switched to DRV/r with a detectable viral load. Only one of these patients was undetectable at week 48 and only three ever achieved an undetectable viral load on DRV/r at any point during the study.

Although toxicity and adherence were the main reasons patients were switched to PI/r monotherapy in these studies, another reason to favour monotherapy is, of course, cost.

In a separate analysis of the results of MONET, a trial of darunavir/r monotherapy, Chelsea and Westminster’s Brian Gazzard and colleagues calculated that the annual drug costs per patient, at London prices, for each patient in the trial was £8642 for patients who remained on triple therapy and £4126 for patients on monotherapy; for each patient who achieved an undetectable viral load the figures were respectively £9085 and £4413.