Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.

OBJECTIVE: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. METHODS: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). RESULTS: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. CONCLUSION: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.

High risk human papillomavirus prevalence and genotype distribution among women infected with HIV in Manaus, Amazonas.

BACKGROUND: Human immunodeficiency virus (HIV)-positive women have a high prevalence of human papillomavirus (HPV), and are infected with a broader range of HPV types than HIV-negative women. We aimed to determine the prevalence of cervical cytologic abnormalities, high-risk (HR)-HPV prevalence, type distribution according to the severity of cervical lesions and CD4 cell count and identify factors associated with HR-HPV infection among women living with HIV in Manaus, Amazonas. METHODS: We enrolled 325 women living with HIV that attended an infectious diseases referral hospital. Each woman underwent a gynecological exam, cervical cytology, HR-HPV detection by Polymerase chain Reaction (PCR) using the BD Onclarity™ HPV Assay, colposcopy and biopsy, when necessary. We assessed the associations between potential risk factors and HR-HPV infection. RESULTS: Overall, 299 (92.0%) women had a PCR result. The prevalence of HR-HPV- infection was 31.1%. The most prevalent HR-HPV types were: 56/59/66 (32.2%), 35/39/68 (28.0%), 52 (21.5%), 16 (19.4%), and 45 (12.9%). Among the women with HR-HPV infection (n = 93), 43.0% had multiple infections. Women with HPV infection showed higher prevalence of cervical abnormalities than that HPV-negative (LSIL: 22.6% vs. 1.5%; HSIL: 10.8% vs. 0.0%). The prevalence of HR-HPV among women with cytological abnormalities was 87.5% for LSIL and 100.0% for HSIL. Women with CD4 < 200 cell/mm3 showed the highest HR-HPV prevalence (59.3%) although this trend was not statistically significant (p-value = 0.62). The mean CD4 cell count decreased with increasing severity of cervical lesions (p-value = 0.001). The multivariable analysis showed that increasing age was associated with a decreased risk of HR-HPV infection with an adjusted prevalence odds ratio of 0.9 (95.0% CI: 0.9-1.0, p-value: 0.03) for each additional year. The only factor statistically significant associated with HR-HPV infection was CD4 cell count. CONCLUSIONS: HR-HPV and abnormal cytology prevalence are high among women in the Amazonas. The low CD4 cell count was an important determinant of HPV infection and abnormal cytological findings. HPV quadrivalent vaccination used in Brazil might not offer protection for an important fraction of HPV-related disease burden in women living with HIV. This is partly explained by the high presence of non targeted vaccine HR-HPVs, such as the HPV genotype groups 56/59/66, 35/39/68 and individually HPV-52 and HPV-45, some of which contribute to high-grade lesion.