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A pilot study evaluates the safety and noninferiority and explores the efficacy of administration of once-daily versus twice-daily lopinavir/ritonavir (LPV/r) in antiretroviral-naive HIV-1-infected subjects. During 48 weeks, a once-daily regimen of lopinavir/ritonavir + tenofovir disoproxil fumarate + emtricitabine appears to contain similar virologic and immunologic responses in antiretroviral-naive subjects as the same region with lopinavir/ritonavir administered twice daily.

Combination antiretroviral therapy (ART) with two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI) significantly improved the prognosis of patients with HIV. Nevertheless, the usefulness of the first PIs was sometimes compromised by poor tolerability, high pill burden, frequent dosing, and food and fluid restrictions. Consequently, initial ART choices evolved toward simpler PI-sparing regimens incorporating non-nucleoside reverse transcriptase inhibitors or triple NRTIs. Because these PI-sparing alternatives also are imperfect, interest in PI-based approaches to initial therapy remains, especially in light of newer PIs that have a more favorable tolerability profile. The better safety and tolerability attributes of the newer PIs suggest that highly effective therapy can be administered while preserving patients' health-related quality of life. As long as the virologic activity of these newer PIs is comparable to that of existing options, differentiating features beyond efficacy are important in the choice of an appropriate treatment regimen for patients with HIV.

Abstract Background Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA Results 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1–4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA Conclusions APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.

Background: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -- experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. Results: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/ 118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1-4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. Conclusions: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable. [ABSTRACT FROM AUTHOR]

Presents a case report of mesenteric small bowel infarction associated with antithrombin deficiency. Results of the examination of a woman presented with a history of abdominal pain; Discussion on small bowel infarction resulting from venous thrombosis; Treatment for thrombotic episodes associated with antithrombin deficiency.

Abstract: Ibalizumab, a humanized monoclonal antibody targeting CD4, blocks HIV-1 entry into cells and is the first Food and Drug Adminstration-approved long-acting agent for HIV-1 treatment. In this phase 2a study, 82 HIV-infected adults failing antiretroviral therapy were assigned an individually optimized background regimen (OBR) and randomized 1:1:1 to arm A (15 mg/kg ibalizumab q2wk), arm B (10 mg/kg weekly for 9 weeks, then q2wk), or placebo. Subjects with an inadequate response at week 16 were permitted to cross over to a new OBR plus 15 mg/kg ibalizumab q2wk. At week 16, viral load (VL) reduction was significantly greater than placebo (0.26 log10) in arms A (1.07 log10; P = 0.002) and B (1.33 log10; P < 0.001); CD4+ T cell counts increased significantly in arm A. After week 16, 11/27 (arm B) and 19/27 (placebo) subjects crossed over to OBR plus 15 mg/kg ibalizumab; 8/28 in arm A initiated a new OBR. Ibalizumab treatment resulted in VL reduction at week 24 (-0.77 and -1.19 log10 for arms A and B, respectively, versus -0.32 log10 for placebo) and 48 weeks (-0.54 and -0.77 versus -0.22 log10). Compared with placebo, VL differences were statistically significant for arm B at week 24 (P = 0.001) and week 48 (P = 0.027). CD4+ T cell counts increased significantly by week 48 in both arm A and arm B, relative to placebo. No ibalizumab-related serious adverse events were reported. The durable antiviral activity and tolerability of ibalizumab support its use in treating individuals harboring multidrug-resistant HIV-1., Competing Interests: R.L.H. is a speaker and consultant of Theratechnologies. S.W. is an employee of TaiMed Biologics USA, Inc. S.T.L. was a former employee and shareholder of TaiMed Biologics USA, Inc. during this clinical study. R.B.C. is an employee of Theratechnologies Inc. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

The development of resistance to antiretroviral therapies has become a formidable barrier to providing optimal treatment of HIV infection in the United States. The emergence of new mutations resistant to antiretroviral agents and a rise in transmission of resistant viruses contribute to an increased risk of treatment failure. Resistance testing of both treatment-experienced and treatment-naive patients i snow recommended for identification of the most effective treatment regimen; however, resistance testing is not universally available or easily interpreted. Furthermore, poor adherence to a treatment regimen or treatment with less potent antiretroviral agents can lead to exposure of virus to subinhibitory levels of drug and the development of resistance. In this article, we discuss several issues that specifically impact the development and transmission of resistant HIV in patients belonging to ethnic minorities and teh implementation of strategies that will overcome resistance as an obstacle to optimal treatment.