Unexpected CD4 decay, hidden adherence gaps, resilience, and the need for long-acting therapy in a single HIV outpatients' cohort.

This single-centre, single-cohort study examines hidden non-adherence to antiretroviral therapy in a setting of persistent optimal viral suppression but concordant absolute and percent CD4 decay by >10% from the previous test. After the finding of important drug holidays in two virologically suppressed patients, between January 2021 and January 2022 all PLWH who fulfilled CD4 decay criteria were asked for how long therapy was interrupted, how many days before re-testing CD4 and HIV RNA was it resumed and the reason for interruption. Of 668 HIV-infected subjects, 61 fulfilled the pre-specified criteria for significant CD4 decay and 15 (2.25% of the total, 25% of the CD4 decay group) admitted long-lasting treatment interruptions, compensated by treatment resumption before the subsequent testing. Eleven treatment interruptions exceeded 28 days, and none was shorter than 15 days. CD4 recovery was worse at 6 months in non-adherent subjects (-0.5 vs + 16/mmc, p < 0.0001) and in non adherence vs immune decay time-related with COVID-19 (0 vs + 22/mmc, p < 0.0001). Reasons for interrupting treatment were travel, psychological, poverty-related, addiction and sentimental sphere problems. Long-acting regimens, with stringent control of precision in timely administration, may protect PLWH from damaging their health status and possibly transmit HIV.

Mortality rates among COVID-19 patients hospitalised during the first three waves of the epidemic in Milan, Italy: A prospective observational study.

INTRODUCTION: This paper describes how mortality among hospitalised COVID-19 patients changed during the first three waves of the epidemic in Italy. METHODS: This prospective cohort study used the Kaplan-Meier method to analyse the time-dependent probability of death of all of the patients admitted to a COVID-19 referral centre in Milan, Italy, during the three consecutive periods of: 21 February-31 July 2020 (first wave, W1), 1 August 2020-31 January 2021 (second wave, W2), and 1 February-30 April 2021 (third wave, W3). Cox models were used to examine the association between death and the period of admission after adjusting for age, biological sex, the time from symptom onset to admission, disease severity upon admission, obesity, and the comorbidity burden. RESULTS: Of the 2,023 COVID-19 patients admitted to our hospital during the study period, 553 (27.3%) were admitted during W1, 838 (41.5%) during W2, and 632 (31.2%) during W3. The crude mortality rate during W1, W2 and W3 was respectively 21.3%, 23.7% and 15.8%. After adjusting for potential confounders, hospitalisation during W2 or W3 was independently associated with a significantly lower risk of death than hospitalisation during W1 (adjusted hazard ratios [AHRs]: 0.75, 95% confidence interval [CI] 0.59-0.95, and 0.58, 95% CI 0.44-0.77). Among the patients aged >75 years, there was no significant difference in the probability of death during the three waves (AHRs during W2 and W3 vs W1: 0.93, 95% CI 0.65-1.33, and 0.88, 95% CI 0.59-1.32), whereas those presenting with critical disease during W2 and W3 were at significantly lower risk of dying than those admitted during W1 (AHRs 0.61, 95% CI 0.43-0.88, and 0.44, 95% CI 0.28-0.70). CONCLUSIONS: Hospitalisation during W2 and W3 was associated with a reduced risk of COVID-19 death in comparison with W1, but there was no difference in survival probability in patients aged >75 years.

Emerging drugs for the treatment of HIV/AIDS: a review of 2019/2020 phase II and III trials.

Introduction: The study of emerging drug trials to treat people living with HIV (PLWH) helps to understand any advantages and disadvantages of therapies that will be available on the market in the short-term future as well as the mechanisms underlying a better cure.Areas covered: This review analyzes phase 2 and 3 clinical trials published between 2019 and 2020 concerning six different emerging drugs. The majority of the trials focus on long acting drugs, but also on new orally administered compounds.Expert opinion: The biggest news in antiretroviral therapy (ART) is the approval of cabotegravir/rilpivirine as a complete long-acting (LA) therapeutic regimen. It paves the way for an innovation that may change the paradigms of HIV treatment in the long term, albeit it will not be obvious to implement and treatment adherence still needs to be fully evaluated. Results of phase 3 Islatravir trials are awaited. Lenacapavir may soon reach phase 3. These drugs may pave the way for 6-month ART in the next future. Fostemsavir has been recently approved. Albuvirtide, a fusion inhibitor approved in China, presents several limitations for its intravenous use only. UB-421 and VRC01 are monoclonal antibodies against HIV. This emerging technology has shown interesting results but needs further studies.