Catherine Crenn-Hebert

Comparative prevalence, incidence and short-term prognosis of cervical squamous intraepithelial lesions amongst Hiv-positive and Hiv-negative women

Objective: To investigate the impact of HIV infection on the prevalence, incidence and short‐term prognosis of squamous intraepithelial lesions (SIL), in a prospective study with 1‐year follow‐up. Methods: Between 1993 and 1995, 271 HIV‐positive and 171 HIV‐negative women at high risk of HIV infection were recruited, 365 (82.6%) of whom completed the 1‐year follow‐up. The women underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. Results: The SIL prevalence ranged from 7.5% for HIV‐negative to 31.3% for HIV‐positive women with CD4 cell counts < 500 × 106/l (P < 0.001). Other factors associated independently and significantly with SIL prevalence were HPV‐16, 18, 33 and related types, HPV‐31, ‐35, ‐39 and related types, lifetime number of partners, younger age, past history of SIL and lack of past cervical screening. The SIL incidence ranged from 4.9% in HIV‐negative women to 27% in HIV‐positive women with CD4 cells < 500 × 106/l (P < 0.001). Progression from low‐ to high‐grade SIL during follow‐up was detected in 38.1% of HIV‐positive women with CD4 cells ≤ 500 × 106/l but in no HIV‐negative nor HIV‐positive women with CD4 cells > 500 × 106/l. HPV‐16, 18, 33 and related types were also associated with higher incidence of SIL and progression from low‐ to high‐grade SIL. Conclusion: HIV‐induced immunodeficiency is associated with high prevalence, incidence and persistence/progression of SIL. A pejorative influence of HIV infection without marked immunodeficiency is less clear. HIV‐positive women with SIL may thus benefit from early treatment when a useful immune response is still present.

Atazanavir in pregnancy: impact on neonatal hyperbilirubinemia.

OBJECTIVEnTo study the impact on the neonate of maternal antiretroviral therapy with atazanavir (ATV).nnnSTUDY DESIGNnAn observational study of 22 HIV-infected women receiving, for clinical indications, antiretroviral therapy with ATV 300 mg and ritonavir 100mg during pregnancy and their 23 HIV infants (including a twin pair).nnnRESULTSnMothers had received ATV for a median duration of 19 months [range 3-49] by delivery. At delivery, plasma HIV-RNA was <40 copies/mL in all patients. Liver enzymes were normal in 19/22 patients, but one woman had grade 3-4 liver toxicity. Maternal serum bilirubin concentrations were above the upper limit of normal in most patients, with grade 3 toxicity in 5 patients. All but one woman had trough ATV concentrations during pregnancy above the minimum effective concentration. The median cord blood ATV concentration was 130 ng/mL [range<30-758]; the cord/maternal ratio was 21%. All neonates were born at term [median 38.2 weeks]. Three neonates had mildly elevated AST transaminase levels. Bilirubin concentrations at birth were significantly higher than maternal concentrations, with a median of 44 μm/L [range 24-129]; values on days 2-3 were 63 [8-212]. Five neonates had jaundice requiring phototherapy, without liver damage, and recovered without sequelae.nnnCONCLUSIONnNeonates whose mothers were treated with ATV should be monitored for hyperbilirubinemia, which may be due to placental transfer of unconjugated bilirubin from the mother and/or a direct effect of transplacental ATV on bilirubin metabolism in the fetus.

Raltegravir Concentrations in the Genital Tract of HIV-1-Infected Women Treated with a Raltegravir-Containing Regimen (DIVA 01 Study)

ABSTRACT We studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median raltegravir concentrations were 235 ng/ml in BP and 93 ng/ml in CVF, with a CVF/BP ratio of approximately 2.3. This good penetration of raltegravir may contribute to the control of viral replication in the female genital tract.

Prise en charge des femmes enceintes toxicomanes et de leurs enfants

Resume Les enfants de meres toxicomanes presentent un risque eleve de pathologies organiques graves: pathologies perinatales (prematurite, retard de croissance intra-uterin, souffrance fœtale algue, infections) avec leur corllaire de sequelles neurologiques et respiratoires, transmission dinfections materneless en rapport avec la toxicomanie (virus de limmunodeficience humain, virus de lhepatite B et C, syphilis). Un grand mombre dentre eux p resente par alleurs un syndrome de sevrage aux opiaces. Ce syndrome se caracterise par une symptomatologie dagitation et dhyperexcitabilite dautant plus intense et precoce dans la periode neonatale que lintoxication maternelle est plus severe. Il est souvent suivi dune phase de postsevrage de plusieurs semaines avec agitation, troubles du sommeil, cris, difficultes de lalimentation. Sil ne met pas en jeu le pronostic vital, il contribue a rendre ces enfants peu valorisants pour leur mere et perturbe gravement letablissement des interrelations mere-enfant. En depit de ces handicaps, il savere que lavenir de ces depend essentiellement de leur environnement sociofamilial caracterise par de nombreux facteurs negatifs: taux eleve separations mere-enfant, violence, delinquance, precarite, logement insalubre, prostitution, dependance vis-a-vis des drogques, fragilite psychologique des parents, incarceration ou deces du pere et/ou de la mere… Une prise en charge medico-psychosociale specialisee, a debut preoce, de la mere et de lenfant est done indispensable, visant a preserver chaque fois que possible lestablissement dun attachement mere-enfant harmonieux. Vis-a-vis de la mere, il convient de remplacer lattitude frequement repressive par une atitutde de soutien et daccompagnement pendant la grossese, sans faire du sevrage rapide une exigence et de developper les programmers de substitution. Vis-a-vis de lenfant, la seule notion de toxicomanle maternelle ne doit pas etre une indication de placement a priori.

Prevalence of and Risk Factors for Anal Oncogenic Human Papillomavirus Infection Among HIV-Infected Women in France in the Combination Antiretroviral Therapy Era

BACKGROUNDnLittle is known about the type-specific prevalence of anal human papillomavirus (HPV) infection and risk factors for anal high-risk (HR) HPV infection in human immunodeficiency virus (HIV)-infected women.nnnMETHODSnA cross-sectional study of anal and cervical HPV infection was nested within a gynecological cohort of HIV-infected women. Specimens were tested for type-specific DNA using a polymerase chain reaction-based assay.nnnRESULTSnThe study population consisted of 311 women with a median age of 45.3 years, of whom 42.8% originated from sub-Saharan Africa and 96.8% were receiving combination antiretroviral therapy. The median CD4(+)cell count was 612/μL, and the HIV load was <50 copies/mL in 84.1%. HR-HPV types were detected in the anal canal in 148 women (47.6%) and in the cervix in 82 (26.4%). HPV-16 was the most prevalent type in both the anal canal (13.2% of women) and the cervix (5.1%). In multivariable analysis, factors associated with prevalent anal HR-HPV infection were CD4(+)count <350/μL (odds ratio, 2.9; 95% confidence interval, 1.3-6.5), concurrent cervical lesions (2.6; 1.0-4.3), and cervical HR-HPV infection (1.8; 1.0-3.2).nnnCONCLUSIONSnThe high prevalence of HR-HPV types, including HPV-16, in the anal canal of HIV-positive women is concerning. Anal cancer screening should be considered for HIV-positive women as part of their routine care.

Dysplasies cervicales chez les patientes ménopausées infectées par le VIH

INTRODUCTIONnAn increasing number of HIV-1-infected women reaches the age of menopause. This infection is associated with a higher incidence of cervical squamous intraepithelial lesions (low-grade or LSIL, high grade or HSIL). The aim of our study was to describe the cervical disease in these patients during menopause.nnnPATIENTS AND METHODSnRetrospective study, identifying all Pap smears and colposcopy in HIV-1-infected postmenopausal women between 1995 and 2008, in our hospital.nnnRESULTSnEighteen postmenopausal women, aged of 54 years (43-63), have HIV-1 infection since 7.5 years (2-25). Fifty-one pathological exams were reviewed in which 27 (50.98%) abnormal, including four (7.84%) ASC-US, 15 (29.41%) LSIL lesions, and seven (13.73%) HSIL. Ten patients had surgery (laser, conisation, hysterectomy) during the period. The evolution of cervical lesions was: stability in 40.48%, regression in 35.71% and progression in 23.81%. The median time to develop an HSIL at menopause was 5 years.nnnCONCLUSIONnIn our study, postmenopausal HIV-1-infected women have most frequently LSIL and persistent. Monitoring of these postmenopausal women should be continued, the attitude to realise an initial HPV typing and confirmation of an abnormal annually Pap smear with colposcopic exam should be confirmed by larger study.

Travail originalDysplasies cervicales chez les patientes ménopausées infectées par le VIHCervical disease in postmenopausal HIV-1-infected women

INTRODUCTIONnAn increasing number of HIV-1-infected women reaches the age of menopause. This infection is associated with a higher incidence of cervical squamous intraepithelial lesions (low-grade or LSIL, high grade or HSIL). The aim of our study was to describe the cervical disease in these patients during menopause.nnnPATIENTS AND METHODSnRetrospective study, identifying all Pap smears and colposcopy in HIV-1-infected postmenopausal women between 1995 and 2008, in our hospital.nnnRESULTSnEighteen postmenopausal women, aged of 54 years (43-63), have HIV-1 infection since 7.5 years (2-25). Fifty-one pathological exams were reviewed in which 27 (50.98%) abnormal, including four (7.84%) ASC-US, 15 (29.41%) LSIL lesions, and seven (13.73%) HSIL. Ten patients had surgery (laser, conisation, hysterectomy) during the period. The evolution of cervical lesions was: stability in 40.48%, regression in 35.71% and progression in 23.81%. The median time to develop an HSIL at menopause was 5 years.nnnCONCLUSIONnIn our study, postmenopausal HIV-1-infected women have most frequently LSIL and persistent. Monitoring of these postmenopausal women should be continued, the attitude to realise an initial HPV typing and confirmation of an abnormal annually Pap smear with colposcopic exam should be confirmed by larger study.

Cervical dysplasia in postmenopausal patients infected by HIV

Results In 18 postmenopausal patients, median age 54 years (range 43 to 63) diagnosed with HIV-1 infection for 7,5 years (range 2 to 25), 51 samples were analyzed. There were 27 (50.98%) abnormalities, including 4 (7,84%) ASC-US, 15 (29.41%) low-grade lesions, and 7 (13.73%) high-grade lesions. Ten of these patients underwent surgery (laser, conization, hysterectomy) during this period. During follow-up, the lesions were stable in 40.48%, regressed in 35,71%, and progressed in 23.81%. In our study, the median onset of high-grade dysplasia during menopause is 5 years.