The numbers of PrEP, pre-exposure prophylaxis for HIV infection, in Italy. Target population, implementation limits, risk compensation. The access program ItaPrEP compared to Prevenir Study.

Now, PrEP studies document a secure TDF/FTC administration profile in HIV-negative individuals exposed to the drug. Fonner et al meta-analysis showed no differences in the proportion of adverse events between groups prophylaxis with the drug and placebo groups. In 10 placebos controlled RCT, the overall OR for any adverse event was found to be 1.01 (95%CI 0.99-1.03) and for any grade 3 or 4 adverse event, equal to 1.02 (95%CI 0.92-1.13). The most common adverse events were gastro-intestinal disorders, headache and nausea. In the IPERGAY study, gastro-intestinal disorders were found to be excess in the prophylaxis group compared to placebo (14% vs. 5%, p-0.002), but these results were not confirmed in the cumulative meta-analysis of the published studies. The use of TDF/FTC in PrEP has been associated with a non-progressive live decline in kidney filter values, and in one study, an increase in renal tubular dysfunction markers (alpha-1-microglobulin and proteinuria). It should be mentioned that the kidney alterations are reversible after suspension.

An association between exposure to TDF/FTC during PrEP and a reduction in bone mineral density (BMD)104 was also documented. This alteration is not further progressive after the sixth month of PrEP, is not associated with a higher risk of fractures and is generally reversible after suspension of the TDF/FTC. A recent meta-analysis of Pilkington in coll. out of 14 randomized controlled clinical trials, which included 15,678 participants, for a total of 22,250 follow-up person-years, it showed, in 12 studies, an incidence of severe adverse events of grade 3-4 of 17.4% of people in PrEP vs 16.8% of people taking placebos (p-0.53). The incidence of bone fractures (3.7% in subjects in PrEP vs 3.3% in the controls) was also comparable, and no difference was observed in terms of increased serum creatinine of grade 3-4.