Factors Influencing Adherence to the Risk Management Program for Women With a Genetic Predisposition to Breast Cancer: Real-World Data from a French Multicenter Program.

BACKGROUND: Risk management programs targeting women with genetic predispositions to breast cancer (BC), eg, BRCA1 and BRCA2, are effective assuming full adherence with the program protocol. However, high risk to BC in women and equal access to care may not result in high and uniform adherence with the program. OBJECTIVE: To elucidate factors influencing adherence with screening program in women with genetic predispositions to BC. MATERIAL AND METHODS: We retrieved data from a multicenter pathogenic-related BC surveillance program across 4 French regions. We used multilevel logistic modeling to analyze factors of adherence with the program, with "on-time" or postponed screening as the dependent variable. RESULTS: Seven hundred and seventy-eight participants were followed for a 4.7-year median. We observed 2796 annual screening rounds and 5.4% postponed rounds with a 6-month margin. Women with prevalent BC and carriers of BRCA1 and BRCA2 mutations did not have on-time annual screenings any more than women low cancer risk. Better adherence was observed with screenings after the 2nd round, with higher total number of rounds. Having one or more recalls was significantly associated with worse adherence. No contextual factors affected adherence. Furthermore, postponed rounds increased between 2018 and 2020 compared to 2015 and 2017. CONCLUSION: Having a higher BC risk status does not result in better adherence to the risk management program. However, factors directly related to screening rounds reduced postponements. Future research should address the benefits of screening-related organizational factors that contribute to adherence improvement.

3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme.

Glutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs180) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs180 in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies. Here we show that the mycobacterial L-GDH180 (mL-GDH180) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH180 involve a C-terminal domain that we propose as a new fold and a flexible N-terminal segment comprising ACT-like and PAS-type domains that could act as metabolic sensors for allosteric regulation. These findings uncover unique aspects of the structure-function relationship in the subfamily of L-GDHs.

Long-term virological, immunological and mortality outcomes in a cohort of HIV-infected female sex workers treated with highly active antiretroviral therapy in Africa.

BACKGROUND: Concerns have been raised that marginalised populations may not achieve adequate compliance to antiretroviral therapy. Our objective was to describe the long-term virological, immunological and mortality outcomes of providing highly active antiretroviral therapy (HAART) with strong adherence support to HIV-infected female sex workers (FSWs) in Burkina Faso and contrast outcomes with those obtained in a cohort of regular HIV-infected women. METHODS: Prospective study of FSWs and non-FSWs initiated on HAART between August 2004 and October 2007. Patients were followed monthly for drug adherence (interview and pill count), and at 6-monthly intervals for monitoring CD4 counts and HIV-1 plasma viral loads (PVLs) and clinical events. RESULTS: 95 women, including 47 FSWs, were followed for a median of 32 months (interquartile range [IQR], 20-41). At HAART initiation, the median CD4 count was 147 cells/µl (IQR, 79-183) and 144 cells/µl (100-197), and the mean PVLs were 4.94 log10 copies/ml (95% confidence interval [CI], 4.70-5.18) and 5.15 log10 copies/ml (4.97-5.33), in FSWs and non-FSWs, respectively. Four FSWs died during follow-up (mortality rate: 1.7 per 100 person-years) and none among other women. At 36 months, the median CD4 count increase was 230 cells/µl (IQR, 90-400) in FSWs vs. 284 cells/µl (193-420) in non-FSWs; PVL was undetectable in 81.8% (95% CI, 59.7-94.8) of FSWs vs. 100% (83.9-100) of non-FSWs; and high adherence to HAART (> 95% pills taken) was reported by 83.3% (95% CI, 67.2-93.6), 92.1% (95% CI, 78.6-98.3), and 100% (95% CI, 54.1-100) of FSWs at 6, 12, and 36 months after HAART initiation, respectively, with no statistical difference compared to the pattern observed among non-FSWs. CONCLUSIONS: Clinical and biological benefits of HAART can be maintained over the long-term among FSWs in Africa and could also lead to important public health benefits.

Linking HIV prevention and care for community interventions among high-risk women in Burkina Faso--the ARNS 1222 "Yerelon" cohort.

BACKGROUND: Interventions targeting core groups such as high-risk women in Africa have focused mostly on HIV prevention. In this marginalized group, the delegation of HIV care to public services may jeopardize the effectiveness of prevention activities. We assessed the effect of an intervention combining prevention and care among high-risk women on HIV exposure and treatment outcomes. METHODS: In Burkina Faso, high-risk women were recruited by peer educators in an open-cohort study with 4-monthly follow-up visits. Primary prevention included peer-led information, education and communication sessions, condom distribution, regular HIV counselling and testing, and sexually transmitted infections management. Participants were offered free medical care including antiretroviral therapy (ART) and treatment adherence support by psychologists. RESULTS: From December 2003, 658 high-risk women were enrolled and followed up for a median 20.8 months. Seven of the 489 HIV-uninfected women seroconverted (HIV incidence 0.9 of 100 person-years, 95% confidence interval: 0.24 to 1.58). HIV incidence tended to be higher during the first 8 months of follow-up than thereafter (1.43 vs. 0.39 per 100 person-years). Among 47 of 169 HIV-seropositive women who started ART, 79.4% achieved undetectable plasma viral load 6 months after initiation and 81.8% at 36 months. Condom use at last sexual intercourse with clients increased from 81.7% at enrollment to 98.2% at 12 months (P < 0.001) and from 67.2% to 95.9% (P < 0.001) with regular clients. CONCLUSIONS: The integration of HIV care services, including the provision and support of ART, with a peer-led primary prevention package is pivotal to reduce HIV incidence and is likely to modify the local HIV dynamics.

Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study.

BACKGROUND: Human papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology. METHODS: A prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrollment. RESULTS: Genital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/µL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ≤ 200 cells/µL. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts. CONCLUSIONS: Genital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population.

Presence of CRF09_cpx and complex CRF02_AG/CRF09_cpx recombinant HIV type 1 strains in Côte d'Ivoire, West Africa.

Based on partial env and pol (protease and RT) subtyping, we recently documented that the majority (>80%) of the HIV-1 strains that circulate in Côte d'Ivoire were CRF02_AG and about 11% were recombinants or could not be clearly assigned to a known subtype or CRF. In order to determine in more detail the precise structure of these viruses we sequenced the full-length genomes for six such strains. Bootscan and phylogenetic tree analysis showed that four strains were complex and unique CRF02_AG/CRF09_cpx recombinants, one was a CRF02_AG/CRF06_cpx recombinant, and one was a pure CRF09_cpx. Reanalysis of the remaining recombinants asserted the predominance of CRF09_cpx within intersubtype recombinants and circulation of CRF09_cpx in Côte d'Ivoire. More detailed analysis of the CRF09_cpx strains revealed also that part of the pol gene belonged to subtype K. This is the first time that such recombinants are described.

Behavior assessment of blood donors facing the risk of HIV infection, Abidjan, Cotê D'Ivoire, 2001-2002.

Despite precautions taken to guarantee blood safety, in the National Blood Transfusion Center (CNTS) of Abidjan, about 30 regular blood donors are detected with HIV seroconversion each year, two-thirds of them men. A survey through face-to-face interviews was carried out at the CNTS of Abidjan from September 2001 to March 2002 among HIV-positive and HIV-negative regular blood donors, informed about their serologic status. HIV-negative regular blood donors informed about their serologic status since a median time of 67 months (n = 50) disclosed more risky behaviors such as multiple sexual partners (68%) than HIV-positive blood donors informed about their status (n = 112) since a median time of 35 months (41%) (P < 0.001). Condoms were systematically used by 17% of HIV-negative blood donors and 55% of HIV-positive blood donors (P < 0.001). Enhanced counseling and awareness could reduce in the future the number of cases of seroconversion among regular blood donors and improve their subsequent behavior. Blood donors who have unprotected sex with partners of unknown HIV serologic status and especially with casual partners are strongly exposed to HIV transmission and should be discouraged to continue giving blood, after adequate counseling.

Determinants of allogeneic transfusion among patients who had an autologous blood procedure, France.

Autologous transfusion techniques have been proposed to decrease viral contamination related to allogeneic transfusion. Epidemiological studies looking at the actual effect of such policy are scarce. The aim of this study was to assess factors associated to the transfusion of additional allogeneic units among autologous blood recipients in France. We used a subgroup of data of RECEPT, a representative study of transfusion in French hospitals, and described blood recipients and components during the first 24 hours following a transfusion in 175 teaching and non teaching hospitals. We analysed data regarding patients included in the original study, who received autologous blood transfusion (376 patients). Almost one fifth of patients transfused with autologous blood was exposed to additional allogeneic transfusion. Patients undergoing cardiovascular surgery and who were transfused with blood salvage received allogeneic transfusion more frequently than patients undergoing orthopaedic surgery. Further implication of epidemiologists in studies of transfusion or other health technologies could help better formulate policies purported at decreasing risks.

Presence of key drug resistance mutations in isolates from untreated patients of Abidjan, Côte d'Ivoire: ANRS 1257 study.

A total of 107 HIV-1 isolates from untreated adult patients recruited in Abidjan, CMte d'Ivoire, in 2001 and 2002 were sequenced in the env, reverse transcriptase (RT), and protease genes. The results show that CRF02_AG is still predominant in this west African population; key mutations of resistance to antiretroviral drugs (NRTI, NNRTI, and PIs) were detected in 5.6% of the patients. We hypothesize that these resistant mutants have been acquired through horizontal transmission. Compared to a previous study carried out by our group in 1997-2000 in a similar population of Abidjan, it seems that there is a dynamic process of resistance and that a survey will be necessary.