Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study

Boyd, Mark; Kumarasamy, N.; Moore, Christopher; Nwizu, Chidi; Losso, Marcelo; Mohapi, Lerato; Martin, Allison; Kerr, Stephen J.; Sohn, Annette H.; Teppler, Hedy; Steen, Olivier Van de; Jm, Molina; Emery, Sean; Cooper, David A.

doi:10.1016/s0140-6736(13)61164-2

Cited by 144 publications

(79 citation statements)

References 16 publications

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“…8 Further work comparing the efficacy of LPV/r monotherapy, and other treatment simplification measures, to currently recommended second-line ART is in progress. 38-42 …”

Section: Discussionmentioning

confidence: 99%

Efficacy of Second-Line Antiretroviral Therapy Among People Living With HIV/AIDS in Asia

Boettiger¹,

Durier³

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources it is important to optimize the timing of second-line ART initiation and use the most effective compounds available. Methods HIV positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated. Results There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells/mm3, and median HIV viral load was 16,224 copies/mL. Patients started second-line ART before 2007 (n=105), 2007-2010 (n=147) and after 2010 (n=50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95%CI 7.1 to 10.9) and 1.1 (95%CI 0.6 to 1.9), respectively. Older age, high baseline viral load and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure. Conclusions Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.

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“…8 Further work comparing the efficacy of LPV/r monotherapy, and other treatment simplification measures, to currently recommended second-line ART is in progress. 38-42 …”

Section: Discussionmentioning

confidence: 99%

Efficacy of Second-Line Antiretroviral Therapy Among People Living With HIV/AIDS in Asia

Boettiger¹,

Durier³

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Results of the multi-national SECOND-LINE study in adults indicate high rates of suppression (~80%) on standard NRTI backbone second-line regimens were non-inferior to a nucleoside-sparing regimen. This finding offers reassurance that standard second-line therapies have reasonable success even in settings with prolonged periods of unsuppressed viremia [6]. Another adult study found that approximately 22% of patients receiving second-line therapy did not achieve HIV RNA suppression by six months, citing poor adherence rather than HIV drug resistance as the cause of most failures [25].…”

Section: Discussionmentioning

confidence: 99%

“…Unsuppressed viremia leads to accumulation of resistance mutations and patients monitored by clinical or immunologic criteria tend to have increased durations of unsuppressed viremia compared to those monitored with viral load [5]. Despite this limitation, a majority of adults in resource-limited settings have attained virologic suppression on second-line regimens, even in the context of clinical or immunologically driven monitoring strategies [6],[7]. The utility and cost/benefit of obtaining viral load and/or resistance profiles in such settings is controversial [8]-[10].…”

Section: Introductionmentioning

confidence: 99%

Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up

et al. 2014

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BackgroundIn Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up.MethodsThis was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained.Results161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01).ConclusionsAfter viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0567-3) contains supplementary material, which is available to authorized users.

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“…The SECOND LINE study investigated treatment-experienced HIV-infected patients who failed firstline therapy and were then randomized to receive ritonavir-boosted lopinavir plus two or three NRTIs or raltegravir. After 48 weeks on the new regimen, total cholesterol, LDL, and HDL increased significantly in the raltegravir group, while there was no significant change in triglycerides (37). The SWITCHMRK trial demonstrated marked reduction in total cholesterol, non-HDL cholesterol, and triglycerides at 12 weeks in ART-experienced patients that were switched from a regimen that included lopinavir/ritonavir to raltegravir.…”

Section: Integrase Inhibitorsmentioning

confidence: 97%

MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

Srinivasa

Grinspoon

2014

European Journal of Endocrinology

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In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50 years, and in that regard, the use of ART has transformed HIV into a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear but may be related to a complex interaction between long-term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors (PIs) and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer PIs, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks.

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Cited by 144 publications

References 16 publications

Efficacy of Second-Line Antiretroviral Therapy Among People Living With HIV/AIDS in Asia

Efficacy of Second-Line Antiretroviral Therapy Among People Living With HIV/AIDS in Asia

Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up

MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

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