Yannick Manigart

Sustained Viral Suppression and Higher CD4+ T-Cell Count Reduces the Risk of Persistent Cervical High-Risk Human Papillomavirus Infection in HIV-Positive Women

BACKGROUND Studies analyzing the impact of combination antiretroviral therapy (cART) on cervical infection with high-risk human papillomavirus (HR-HPV) have generated conflicting results. We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months. METHODS Prospective cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011. RESULTS At baseline, the median age was 38 years, the race/ethnic origin was sub-Sarahan Africa for 84%, the median CD4(+) T-cell count was 426 cells/µL, 79% were receiving cART, and the HR-HPV prevalence was 43%. The median interval of having had an HIV load of <50 copies/mL was 40.6 months at the time of a HR-HPV-negative test result, compared with 17 months at the time of a HR-HPV-positive test result (P < .0001, by univariate analysis). The median interval of having had a CD4(+) T-cell count of >500 cells/µL was 18.4 months at the time of a HR-HPV-negative test result, compared with 4.45 months at the time of a HR-HPV-positive test result (P < .0001). In multivariate analysis, having had an HIV load of <50 copies/mL for >40 months (odds ratio [OR], 0.81; 95% confidence interval [CI], .76-.86; P < .0001) and having had a CD4(+) T-cell count of >500 cells/µL for >18 months (OR, 0.88; 95% CI, .82-.94; P = .0002) were associated with a significantly decreased risk of HR-HPV infection. CONCLUSION Sustained HIV suppression for >40 months and a sustained CD4(+) T-cell count of >500 cells/µL for >18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection.

Topical treatment of CIN 2+ by cidofovir: Results of a phase II, double-blind, prospective, placebo-controlled study

OBJECTIVE Randomized controlled trial evaluating a topical treatment for cervical intraepithelial neoplasia 2 and 3 (CIN 2+) using cidofovir. METHODS Fifty-three women with a biopsy-proven CIN 2+ were randomly assigned, 6 weeks before their planned conisation, either 3 applications of 3 ml 2% cidofovir in Intrasite gel in a cervical cap or a placebo (the same volume of Intrasite alone). A cervical sample for high-risk types of human papillomaviruses (HPV) (Hybrid Capture 2 or HC2) was taken before treatment and before conisation. The cone was submitted for pathological examination, and subsequently, along with the initial biopsy, to in situ hybridization (ISH) for high-risk HPV. RESULTS Forty-eight patients were treated and followed according to the protocol, (23 cidofovir, and 25 placebo). Fourteen of the 23 cones were free of any CIN (60.8%) in the cidofovir group. Only 5 of 25 cones were free of any CIN (20%) in the placebo group (p<0.01). The difference remained significant in the ITT group (p<0.05). In the per-protocol and ITT populations, we observed more frequent viral clearance in the cidofovir group, but the difference was significant only when evaluated by ISH and not by HC2. No systemic toxicity was observed. Cervico-vaginal side effects of cidofovir were limited, and not statistically different from placebo. CONCLUSION The medical topical treatment with cidofovir, at this point, cannot replace conisation, but it is a promising candidate for topical chemotherapy of CIN 2+ lesions; a larger prospective randomized study is needed to confirm our results.

High-risk human papillomavirus infection in HIV-positive African women living in Europe

Cervical infection with high‐risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV‐positive women living in Belgium.

High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus.

Background:Worldwide, human papillomavirus (HPV) 16 and 18 represents 70% of high-risk (HR) HPV found in cervical cancer. However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 (OHR). We aimed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines. Methods:HRHPV genotypes by PCR and cytology were assessed in cervical samples from 508 HIV-positive women prospectively followed in Brussels. Results:Women characteristics were as follows: African origin (84%), median age 42 years, median CD4+ T 555/&mgr;l, 89% under combined antiretroviral therapy and 73% with HIVRNA less than 20 copies/ml. HRHPV prevalence was 23% (116/508): 38% had abnormal cytology, 76% carried OHR without HPV 16 or 18 and 11% had concomitant infection by OHR and HPV 16 or 18. The most frequent HRHPV were HPV52 (19.8%), HPV18 (14.6%), HPV31/35/51/58 (12.1% each), HPV56 (9.9%) and HPV16 (9.5%). Less than 30% of women had their HRHPV genotypes included in the bivalent or quadrivalent vaccines against HRHPV 16 and 18; however, 79% had their HRHPV covered by the ninevalent vaccine against HRHPV 16/18/31/33/45/52/58. Conclusion:The HRHPV genotypes distribution found in these women living in Europe with a successfully treated HIV is similar to the one found in Central Africa with HRHPV other than HPV16 or 18 retrieved in 87%. In this population, the bivalent or quadrivalent vaccines could offer protection in only 30% of women; however this protection could be extended up to 80% with the ninevalent vaccine.

The use of selective progestin receptor modulators (SPRMs) and more specifically ulipristal acetate in the practice of gynaecology

This review discusses the development of selective progestin receptor modulators (SPRMs) for use in womens health and specifically the use of ulipristal acetate (UPA) as emergency contraception (EC) and as a treatment for symptomatic fibroids in women who want to preserve their fertility or avoid a hysterectomy. As an EC, UPA 30 mg should be recommended for women, within 102 h of unprotected intercourse. As a treatment of fibroids, UPA (5 mg daily dose) should be administered for periods of three months as a pre‐surgical strategy, reducing bleeding and fibroid size and facilitating surgery. A proportion of these patients may even avoid surgery. Future developments will demonstrate whether UPA can be used for other indications such as endometriosis and breast cancer prevention or treatment.

In vitro fertilization when men, women, or both partners are positive for HIV: a case–control study

PurposeThe aim of this study was to compare the outcomes of in vitro fertilization (IVF) for couples where one or both partners were positive for the human immunodeficiency virus (HIV) to matched control couples.MethodsA matched case–control retrospective study was performed. Data for 104 couples where the woman was HIV-positive; for 90 couples where the man was HIV-positive; and for 33 couples where both partners were HIV-positive were prospectively analyzed in comparison to matched controls treated in our center during the same period. The main outcomes were clinical pregnancy and live birth rates.ResultsFor couples involving an HIV-positive man, clinical outcomes were comparable to controls and resulted in the birth of 18 healthy babies after 90 cycles. When the woman was affected, cycle cancelation, number of retrieved oocytes, and on-going clinical pregnancy rates per transfer were statistically reduced. Implantation rates were comparable to those of non-affected controls. Seven healthy babies for 104 cycles were obtained. For a couple in which both partners were HIV-positive, only one healthy birth occurred after 33 cycles. Pregnancy rates were systematically reduced though not significantly probably due to sample size.ConclusionsOur data suggest that IVF outcomes were similar to controls when men were HIV-positive and remain acceptable when women were HIV-positive. IVF outcomes were severely reduced in our sero-concordant couples; however, many patients had severe HIV disease previously, and therefore, these results should be reassessed in patients treated early in their disease.

Acceptance of HIV-infected patients in assisted reproductive technique protocols

OBJECTIVE To assess the adequacy of a multidisciplinary approach providing information to couples affected by HIV before ART. DESIGN Prospective observational study. SETTING RT centre and infectious disease clinic, public university hospital. PATIENTS 50 couples with at least one HIV-infected partner. INTERVENTIONS Multidisciplinary approach towards ART by various intervening physicians (specialist in fertility, infectious diseases, paediatrics, obstetrics, psychiatry). MAIN OUTCOME MEASURED We analysed specifically the cases in which the staff did not accept and the patients compliance to the counselling procedures. RESULTS Among the 150 couples, 30 did not complete the procedure and were lost to follow-up. The remaining 120 couples were evaluated: 89 couples were accepted, 5 were temporarily refused and 26 were refused definitively. The major reasons for refusal were medical reasons (n=13). CONCLUSION Because of the high refusal rate and the drop of rate, a multidisciplinary approach is mandatory before initiating ART in seropositive couples.

Impact of HIV treatment on clearance of human papillomavirus (HPV) infection in HIV-infected women

Methods A systematic screening program of oncogenic HPV infection has been initiated in 2002 in HIV+ women; oncogenic HPV was detected by Hybrid Capture II (Digene®) amplification test performed on cervical smears. Women were classified in three groups based on their screening test: N = negative for HPV; P = positive HPV and no cervical high-grade dysplasic lesion; PN = positive HPV then negative on follow-up (FU). The three groups were compared in terms of demographics, CD4, viral load (VL), HIV history and HAART.