Diversity of high risk human papilloma viruses in women treated with antiretroviral and in healthy controls and discordance with cervical dysplasia in the South of Benin.

BACKGROUND: High risk oncologic Human Papilloma Virus (HPV) is one of the leading causes of cervical cancer worldwide. We investigated HPV genotypes among women living or not with Human Immuno-deficiency Virus (HIV) in two major hospitals in the south of the republic of BENIN in the city of Cotonou. Our objective is to investigate the association of high risk-HPV to cervical dysplasia among women under stringent anti-retroviral (ARV) treatment and in controls without HIV. METHODS: The investigation was carried out within 1 year period in two groups of adult women: one group with HIV1 infection and under ARV therapy in the National University Hospital (CNHU-HKM) designated as CH group (n = 86); and one control group without HIV infection and attending the hospital Mènontin for routine gynecologic checkup and designated as ME group (n = 86). Cells derived from cervical uterine smears (CUS) were used for this investigation. The samples in ME group were selected to have similar lamin A/C profile with CH group. HPV genotypes were assessed by polymerase chain reaction (PCR) while lamin A/C expression profile was assessed by western blotting to corroborate the risk of cervical dysplasia. RESULTS: HPV56 is dominant in CH group while HPV66 is dominant in ME group. 31 % of women in CH group are infected with HPV compared to 23 % in ME group. Quadruple and quintuple HPV infections are more observed among CH group but not in ME group making HPV counts of 43 in CH group and 27 in ME group. Cervical dysplasia are present in 5 % (4/86) of women in CH group and in 1 % (1/86) of women in ME group at the time of CUS collection. The adjustment of the risk to develop cervical cancer in the future related to HPV infection and the total loss of lamin A/C is not significantly different in both groups. CONCLUSION: Women living with HIV are more sensitive to multiple HPV infection but not all HPV infections generated cervical dysplasia. The effectiveness of antiretroviral therapy in CH group may reduce significantly the frequency of cervical dysplasia.

Lamin A/C deficiency is an independent risk factor for cervical cancer.

BACKGROUND: In the past, cervical cancer has been linked to Human Papilloma Virus (HPV) infection. Previously, we found that pre-neoplastic breast and ovarian lesions may be associated with lamin A/C deficiency, resulting in abnormal nuclear morphologies and chromosomal instability. Ultimately, these phenomena are thought to lead to cancer. Here, we assessed lamin A/C deficiency as an indicator for the risk to develop cervical cancer. METHODS: The expression of lamin A/C was assessed by Western blotting in cervical uterine smears (CUS) of 76 adult women from Benin concomitant with nuclear morphology assessment and HPV genotyping using microscopy and PCR-based assays, respectively. In vitro analyses were performed to uncover the mechanism underlying lamin A/C expression alterations observed in vivo. The presence of cervical intra-epithelial neoplasia (CIN) was assessed by colposcopy. RESULTS: Normal lamin A/C expression (group A) was observed in 39% of the CUS, weak lamin A/C expression (group B) was observed in 28% of the CUS and no lamin A/C expression (group C) was observed in 33% of the CUS tested. Infection with oncogenic HPV was found to be significantly higher in group C (36%) than in groups A (17%) and B (14%). Two years after our first assessment, CIN was observed in 20% of the women in group C. The in vitro application of either a histone deacetylase inhibitor (trichostatin) or a protein kinase inhibitor (staurosporine) was found to restore lamin A/C expression in cervical cancer-derived cells. CONCLUSION: Lamin A/C deficiency may serve as an independent risk factor for CIN development and as an indicator for preventive therapy in cervical cancer.

Tolerability of mefloquine intermittent preventive treatment for malaria in HIV-infected pregnant women in Benin.

OBJECTIVE: To investigate the tolerability of mefloquine intermittent preventive treatment (MQ IPTp) for malaria in HIV-infected pregnant women compared with HIV-negative women. DESIGN: Prospective cohort study comparing samples of HIV-negative and HIV-infected pregnant women from 2 clinical trials conducted in Benin. METHODS: One hundred and three HIV-infected women from the ongoing PACOME trial were compared with 421 HIV-negative women from a former trial, both trials aiming to evaluate the efficacy and tolerability of MQ IPTp, administered at the dose of 15 mg/kg. Descriptive analysis compared the proportion of women reporting at least 1 adverse reaction, according to HIV status. Multilevel logistic regression identified factors associated with the probability of reporting an adverse reaction for each MQ intake. RESULTS: Dizziness and vomiting were the most frequent adverse reactions. Adverse reactions were less frequent in HIV-infected women (65% versus 78%, P = 0.009). In multilevel analysis, HIV infection [odds ratio (OR) = 0.23, 95% confidence interval (CI) = 0.08 to 0.61] decreased the risk for adverse reactions, whereas detectable viral load (OR = 2.46, 95% CI = 1.07 to 5.66), first intake (versus further intakes, OR = 5.26, 95% CI = 3.70 to 7.14), older age (OR = 1.62, 95% CI = 1.13 to 2.32), and higher education level (OR = 1.71, 95% CI = 1.12 to 2.61) increased the risk. Moderate and severe adverse reactions were more frequent when antiretrovirals were started concomitantly with a MQ intake. CONCLUSIONS: This study provides reassuring data on the use of MQ IPTp in HIV-infected pregnant women. However frequent, adverse reactions remained moderate and did not impair adherence to MQ IPTp. In this high-risk group, MQ might be an acceptable alternative in case sulfadoxine-pyrimethamine loses its efficacy for intermittent preventive treatment.