Thrombosis has been considered an uncommon complication in patients with AIDS. In a 42-month period, 28 adult male homosexuals with AIDS experienced 34 thrombotic events. All but three received HAART regimen, two a successful round of double nucleoside analog therapy, and one patient received no treatment. Median age of group was 38.5 years (range, 24 to 56 years). Median time from HIV infection to thrombosis was 40.5 months (range, 3 to 108 months). No patient had previous thrombosis, family history of thrombosis, or prothrombotic conditions. There were 31 deep vein thromboses, two pulmonary thromboembolisms, and one renal vein thrombosis. Six patients had two thrombotic events. The rate of thrombosis during the 42-month study period was 1.52% (cumulative incidence = 0.30%/year), while the rate of thrombosis in 600 patients before the era of protease inhibitor therapy was 0.33% (cumulative incidence approximately 0.055%/year) (p < 0.001). Due to high incidence of thrombotic recurrences and hemorrhagic complications while using oral anticoagulants, acetylsalicylic acid was initiated; no thrombotic episodes were recorded while using this drug. Protein C and protein S deficiency were found in nine and two patients, respectively. Two patients had lupus anticoagulant and two activated protein C resistance (APCR) without FV Leiden mutation (APCR test was negative after initial screening). Fifteen patients had no thrombophilic abnormalities. These data suggest that protease inhibitors could be a risk factor for venous thrombosis not due to thrombophilic abnormalities but likely related to abnormalities in platelets or endothelium.

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Objectives: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. Design: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). Methods: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4 + T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4 + T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc). Results: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4 + T-cell count increases were comparable across subgroups. Participants with baseline CD4 + T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4 + T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups. Conclusion: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options.

The aim of this report is to describe five patients with lamivudine-induced pure red cell aplasia, an association not previously described. We describe patients with unresponsive anemia in whom a complete study including blood cell counts, reticulocyte counts, hemolysis tests, and bone marrow aspiration was performed. Pure red cell aplasia was considered when anemia was associated with normal leukocyte and platelet counts with a corrected reticulocyte count below 1% and less than 5% bone marrow erythroid progenitors in the absence of positive hemolysis tests. Complete remission was considered when bone marrow erythroid progenitors were at least 16%. Five male patients had pure red cell aplasia with a median age of 32 years (range 29 to 37 years). Before lamivudine, they had hemoglobin >11.8 g/dl without transfusion requirements. After receiving the drug, hemoglobin dropped to 5.2 g/dl (4.3 to 6.1 g/dl) with high transfusion requirements and mean bone marrow erythroid progenitors of 1.84% (0 to 4%). Withdrawal of lamivudine was attempted to confirm the diagnosis. Seven weeks after stopping lamivudine, hemoglobin rose up to 12.8 g/dl (11 .3 to 13.8 g/dl) and bone marrow erythroid progenitors increased up to 25.6% (21 to 40%) without transfusion requirements. Lamivudine-induced pure red cell aplasia may be a cause of anemia unresponsive to conventional treatment in AIDS. Since lamivudine use in Mexico has been relatively short, we expect more cases to appear in the future.

In patients with HIV-1 infection, fasting and postoral methionine load plasma homocysteine levels increased after 6 months of antiretroviral treatment. Nutritional abnormalities were not responsible for hyperhomocysteinemia, suggesting that enzymatic disturbances in the metabolic pathways of homocysteine may occur.