Patient-reported tolerability and acceptability of cabotegravir + rilpivirine long-acting injections for the treatment of HIV-1 infection: 96-week results from the randomized LATTE-2 study.

Background: Long-acting (LA) injectable antiretroviral therapy (ART) is a novel modality currently under development as an alternative to daily oral ART.Objective: The LATTE-2 study (ClinicalTrials.gov identifier NCT02120352) showed that cabotegravir LA + rilpivirine LA maintained virologic suppression through 96 weeks and included further exploration of patient-reported treatment outcomes with an LA injectable form of treatment.Methods: Two-hundred and eighty-six virologically suppressed participants on oral cabotegravir + abacavir/lamivudine once-daily tablets (induction period) were randomized to cabotegravir LA + rilpivirine LA once every 4 weeks (n = 115), once every 8 weeks (n = 115), or the continuation of the oral tablet regimen (n = 56) during the maintenance period. Patient-reported outcome measures included the HIV Medications Questionnaire (HIVMQ) and the HIV Treatment Satisfaction Questionnaire status (HIVTSQ[s]) and change (HIVTSQ[c]) versions at prespecified study visits through Week 96 of the randomized maintenance period.Results: Most participants in the LA injectable groups reported injection-site-related adverse events; however, participants in the 4-week (median HIVTSQ[s] total score, 63.5; post hoc P = 0.02) and 8-week (65.0; post hoc P < 0.001) LA injectable groups were significantly more satisfied with treatment than participants in the oral maintenance group (60.0) at Week 96. This was consistent with results from the HIVTSQ[c] at Week 32, which revealed that participants in both LA groups were significantly more satisfied with therapy compared with patients receiving oral ART (both post hoc P < 0.001).Conclusion: Participants who received LA injectable therapy had high levels of treatment satisfaction and favorably viewed convenience and lifestyle-related aspects of the therapy.

Pulmonary manifestations of malaria : recognition and management.

Lung involvement in malaria has been recognized for more than 200 hundred years, yet our knowledge of its pathogenesis and management is limited. Pulmonary edema is the most severe form of lung involvement. Increased alveolar capillary permeability leading to intravascular fluid loss into the lungs is the main pathophysiologic mechanism. This defines malaria as another cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).Pulmonary edema has been described most often in non-immune individuals with Plasmodium falciparum infections as part of a severe systemic illness or as the main feature of acute malaria. P.vivax and P.ovale have also rarely caused pulmonary edema.Clinically, patients usually present with acute breathlessness that can rapidly progress to respiratory failure either at disease presentation or, interestingly, after treatment when clinical improvement is taking place and the parasitemia is falling. Pregnant women are particularly prone to developing pulmonary edema. Optimal management of malaria-induced ALI/ARDS includes early recognition and diagnosis. Malaria must always be suspected in a returning traveler or a visitor from a malaria-endemic country with an acute febrile illness. Slide microscopy and/or the use of rapid antigen tests are standard diagnostic tools. Malaria must be treated with effective drugs, but current choices are few: e.g. parenteral artemisinins, intravenous quinine or quinidine (in the US only). A recent trial in adults has shown that intravenous artesunate reduces severe malaria mortality by a third compared with adults treated with intravenous quinine. Respiratory compromise should be managed on its merits and may require mechanical ventilation.Patients should be managed in an intensive care unit and particular attention should be paid to the energetic management of other severe malaria complications, notably coma and acute renal failure. ALI/ARDS may also be related to a coincidental bacterial sepsis that may not be clinically obvious. Clinicians should employ a low threshold for starting broad spectrum antibacterials in such patients, after taking pertinent microbiologic specimens. Despite optimal management, the prognosis of severe malaria with ARDS is poor.ALI/ARDS in pediatric malaria appears to be rare. However, falciparum malaria with severe metabolic acidosis or acute pulmonary edema may present with a clinical picture of pneumonia, i.e. with tachypnea, intercostal recession, wheeze or inspiratory crepitations. This results in diagnostic confusion and suboptimal treatment. Whilst this is increasingly being recognized in malaria-endemic countries, clinicians in temperate zones should be aware that malaria may be a possible cause of 'pneumonia' in a visiting or returning child.