Abstract and Introduction
Abstract
Background: HIV treatment recommendations are updated as clinical trials are published. Whether recommendations drive clinicians to change antiretroviral therapy in well-controlled patients is unexplored.
Methods: We selected patients with undetectable viral loads (VLs) on nonrecommended regimens containing double-boosted protease inhibitors (DBPIs), triple-nucleoside reverse transcriptase inhibitors (NRTIs), or didanosine (ddI) plus stavudine (d4T) at publication of the 2006 International AIDS Society recommendations. We compared demographic and clinical characteristics with those of control patients with undetectable VL not on these regimens and examined clinical outcome and reasons for treatment modification.
Results: At inclusion, 104 patients were in the DBPI group, 436 in the triple-NRTI group, and 19 in the ddI/d4T group. By 2010, 28 (29%), 204 (52%), and 1 (5%) patient were still on DBPIs, triple-NRTIs, and ddI plus d4T, respectively. 'Physician decision,' excluding toxicity/virological failure, drove 30% of treatment changes. Predictors of recommendation nonobservance included female sex [adjusted odds ratio (aOR) 2.69, 95% confidence interval (CI) 1 to 7.26; P = 0.01] for DPBIs, and undetectable VL (aOR 3.53, 95% CI 1.6 to 7.8; P = 0.002) and lack of cardiovascular events (aOR 2.93, 95% CI 1.23 to 6.97; P = 0.02) for triple-NRTIs. All patients on DBPIs with documented diabetes or a cardiovascular event changed treatment. Recommendation observance resulted in lower cholesterol values in the DBPI group (P = 0.06), and more patients having undetectable VL (P = 0.02) in the triple-NRTI group.
Conclusion: The physician's decision is the main factor driving change from nonrecommended to recommended regimens, whereas virological suppression is associated with not switching. Positive clinical outcomes observed postswitch underline the importance of observing recommendations, even in well-controlled patients.
Introduction
The introduction of safe and effective combination antiretroviral therapy (cART) has dramatically improved the course of HIV infection. As new agents are developed and introduced into the existing armamentarium, it is a constant requirement of clinicians to remain up to date. Treatment recommendations, compiled by expert panels, are updated regularly as clinical trial data are published, to guide clinicians in their regimen choice.
Some cART combinations are discouraged owing to toxicity, drug interactions, or suboptimal efficacy. Double-boosted protease inhibitor (DBPI) regimens, for example, although previously used as part of salvage treatment in cases of multidrug resistance because of their high genetic barrier to resistance, were subsequently shown to have more side effects than new generation single-boosted PIs such as tipranavir and darunavir. The August 2006 International AIDS Society—USA (IAS-USA) recommendations proposed that DBPI combinations should be avoided accordingly. Triple-nucleoside (or nucleotide) reverse transcriptase inhibitor (NRTI) regimens, whose advantages over nonnucleoside reverse transcriptase inhibitor–or PI-based regimens included minimal drug interactions, ease of use and sparing of PIs and nonnucleoside reverse transcriptase inhibitors for future availability, were prescribed as alternatives for initial therapy. However, the 2004 IAS-USA recommendations discouraged triple-NRTI regimens because of inferior potency (inferior virological control). Finally, the 2004 IAS-USA recommendations discouraged the combination of didanosine (ddI) plus stavudine (d4T), given synergistic toxicity such as peripheral neuropathy, lipodystrophy, pancreatitis, and hyperlactatemia.
Recommendations are also published by the European AIDS Clinical Society (EACS) and the US Department of Health and Human Sciences (DHHS). Considering the cART regimens above, the 2007 EACS guidelines recommend against DBPIs, whereas the DHHS does not mention this combination. Triple-NRTIs were identified as inferior in both the 2003 EACS and the 2004 DHHS recommendations. Finally, the 2003 DHHS recommendations advise against the combination of ddI plus d4T.
Not all clinicians observe treatment recommendations, with inappropriate cART reported in 5%–47% of treatment-naive patients. Patients who are highly treatment experienced, or in whom there are concerns regarding adherence or drug interactions, may be faced with treatment options that are limited or not conforming to recommendations. Regional variation, ethnicity, sex, pretreatment CD4 count, and HIV viral load (VL) have been shown to play a part in guideline nonobservance. Surprisingly, the influence of new recommendations on clinical practice is understudied. To our knowledge, although some studies have examined guideline observance concerning initial cART, no study has analyzed the clinical impact of guideline updates in patients already well controlled on cART.
In Switzerland, the first national treatment recommendations were published in July 2011. Before this, most Swiss HIV physicians, and certainly those at Swiss HIV Cohort Study centers (SHCS; described below), referred to the IAS-USA recommendations (M.C., personal communication). We aimed to determine the impact of the August 2006 IAS-USA recommendations on the prescribing practices of Swiss clinicians by examining patients enrolled in the SHCS who were on nonrecommended regimens at that time.