WHO guidelines on the management of advanced HIV disease. Web Annex B. Systematic review abstracts, GRADE evidence profiles, risk of bias assessments

Abstract Background Kaposi Sarcoma (KS) remains one of the most common cancers in people living with HIV (PLHIV) and is one of the most reported cancers in the general population in sub-Saharan Africa. Moreover, 1-year mortality is up to 41%. We evaluated the evidence on efficacy and safety of treatments for HIVassociated KS to guide treatment recommendations. Methods We systematically searched for randomized controlled trials (RCTs) of treatment of biopsyconfirmed KS among PLHIV published between January 1983 and October 2024. We assessd risk of bias (RoB) using the Cochrane RoB 2 tool, and evidence certainty using GRADE. Results Of 468 articles screened, 21 were RCTs of treatment of HIV-associated KS. Five articles (4 studies, 611 participants) were included in our data synthesis after excluding studies where the comparator was a non-KS specific treatment, or the study was performed prior to highly-active antiretroviral therapy (ART). Meta-analyses were not possible given the data. Paclitaxel had similar progression free survival and 2-year survival as pegylated liposomal doxorubicin (PLD) but had worse grade 1 or 2 peripheral neuropathy: (RR, 2.9; 95%CI 1.0-8.5). Paclitaxel showed greater efficacy, but similar safety profile compared to either etoposide or bleomycin/ vincristine (BV): RR (95%CI) for week 48 progression free survival and grade 3 or 4 adverse events were: 2.5 (1.4-4.4), 0.79 (0.60-1.1) and 1.5 (1.2-1.8), 0.96 (0.74-1.2) respectively. There was no difference in tumour response, quality of life and 3-year survival between gemcitabine and BV. BV had greater grade 3 and 4 peripheral neuropathy, however, this was not statistically significant (RR 1.9, (95% CI 0.71- 5.11). There was no difference in efficacy and safety profile between PLD and liposomal daunorubicin. Overall, for all studies, there were some concerns in the RoB assessment and certainty of evidence was low. Conclusion Among RCTs performed on treatment of HIVassociated KS during the ART era, PLD and paclitaxel have better efficacy compared to other chemotherapeutic agents. There is need for more data on treatment of HIV-associated KS, especially from regions most affected