Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study.

BACKGROUND: In the Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 5 years. METHODS: After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs). RESULTS: At week 256, 186 of 230 (81%) participants in randomized Q8W/Q4W groups and 41 of 44 (93%) participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after week 48. Injection wsite reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant. CONCLUSIONS: Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection.Clinical Trials Registration. NCT02120352.

[Scientific production in infectious diseases in Spain (1991-2001): position within the European Union]. / Producción científica en España en enfermedades infecciosas (1991-2001): posición en el contexto de la Unión Europea.

INTRODUCTION: Medical research in our geographic area has undergone significant changes over the last three decades. The objective of this study was to quantitatively determine Spain's medical research output published in the journals included in the Infectious Diseases section of the Journal Citation Reports, and to compare it with that of other European Union (EU) countries. METHODS: The PubMed Web site (MEDLINE) was used to retrieve medical articles published by authors from Spain and other EU countries from 1991 to 2001 in 36 infectious disease journals included in the Infectious Diseases section of the Journal Citation Reports. RESULTS: We retrieved a total of 17,899 documents published by EU authors during the study period. Authors from Spanish institutions contributed 1,340 documents, 7.5% of the overall EU production. Spain ranked in the sixth position of the EU by number of papers. It remained in the same position after adjusting for gross national product and dropped to the ninth position after correcting for population. The number of articles published increased from 72 in the biennium 1991-1992 to 442 in the biennium 2000-2001. Spanish production rose by 514%, as compared with a median increase of 149% in the other EU countries. Spain was the first producer of articles from the EU in four journals: Diagnostic Microbiology and Infectious Disease (27.6%), European Journal of Clinical Microbiology & Infectious Diseases (24.8%), American Journal of Infection Control (21.8%) and Microbial Drug Resistance (17.5%). CONCLUSIONS: Spanish scientific production in infectious diseases has increased substantially in the period 1991-2001.

[Factors associated with resistance to human immunodeficiency virus protease inhibitors]. / Factores asociados a la resistencia a los inhibidores de la proteasa del virus de la inmunodeficiencia humana.

BACKGROUND: To assess the risk factors associated with genotypic resistance to protease inhibitors (PI) in HIV-infected subjects with virologic failure despite highly active antiretroviral treatment (HAART). PATIENTS AND METHOD: Retrospective chart review including 47 consecutive patients with virologic failure despite PI-based HAART who had undergone a genotypic HIV-1 testing. The prevalence of genotypic resistance to PI was determined and several demographic, clinical and laboratory variables were compared between patients with and without genotypic resistance to those drugs. RESULTS: The entire nucleotide sequence of the protease gene was obtained in 43 of the 47 patients; 18 of them had genotypic resistance to PI. Genotypic resistance to PI was associated with a previous therapy with suboptimal antiretroviral regimens (OR = 10.2; 95% CI, 1.05-245.1; P = 0.02), duration of antiretroviral therapy longer than 18 months (OR = 13.3; 95% CI, 1.23-340.85; P = 0.01), greater number of antiretroviral regimens and drugs before the virologic failure (p < 0.01) and presence of the 184V mutation in the reverse transcriptase gene (OR = 5.6; 95% CI, 1.2-29.2; P = 0.02). There was no relationship between PI resistance and the risk group, viral load or CD4 cell count. In the multivariate analysis, previous therapy with suboptimal antiretroviral regimens was the better predictor of PI resistance (OR = 11.1; 95% CI, 1.04-117.47; P = 0.046). CONCLUSIONS: Patients treated with suboptimal antiretroviral activity regimens before starting HAART can be at greater risk of developing genotypic resistance to protease inhibitors.