Streptococcus pneumoniae, the main cause of community-acquired pneumonia (CAP), also leads to exacerbations, hospitalizations, and mortality in chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF). The risk of CAP is increased in patients with diabetes mellitus (DM), and the risk of invasive pneumococcal disease is increased in HIV-infected patients. Pneumococcal vaccination is recommended for these patients in France. The objective was a large survey of pneumococcal vaccination coverage (PVC) by general practitioners (GPs) in these patients in France. Diagnosis and treatment forms were extracted from the database of 2000 GPs. The GPs and population panels were representative of the metropolitan populations. The primary endpoint was the comparison of PVC in the adult patients diagnosed with COPD, CHF, DM, or HIV infection during the study (April 2013–April 2017) and the control (March 2012–March 2013) periods. Of the 17,865 and 4,690 patients identified, 756 (4%) and 267 (6%) were vaccinated, respectively. During the study period, the PVC was significantly higher (35/282, 12%) in HIV-infected patients and lower in patients with DM (95/5994, 2%) than in other patients. Even though French pneumococcal vaccine recommendations in adults were updated in 2013, the PVC did not increase according to the years of the study period and slightly increased according to time after diagnosis. S. pneumoniae is responsible only for some CAP and meningitis, and incomplete protection by vaccine, hesitancy from practitioners and patients, and the moving schedule of vaccination could explain the results. New tools and/or strategies must be implemented to increase PVC in France. Abbreviations: CAP: community-acquired pneumonia; COPD: chronic obstructive pulmonary diseases; CHF: congestive heart failure; DM: diabetes mellitus; IPD: invasive pneumococcal disease; HIV: human immunodeficiency virus; PVC: pneumococcal vaccination coverage; PCV7: 7-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; GPs: general practitioners; CLM: Cegedim Logiciels Médicaux; MLM: monLogicielMedical; ICD-10: International Classification of Diseases; CNIL: Commission nationale de l’informatique et des libertés; HPV: human papillomavirus; HBV: hepatitis B virus

Objectives > Guidelines recommend routine universal HIV testing in adults to reduce the pool of infected patients unaware of their status, without specific recommendations concerning the method. We compared acceptability and feasibility of HIV testing by ELISA tests or rapid tests from finger-stick whole blood. Methods > Prospective randomized multi-center study comparing acceptability and feasibility of routine universal HIV testing by ELISA tests, with a charge, subsequently reimbursed by Social Security for affiliated patients, or rapid tests from finger-stick whole blood, without any charge from the patients or the general practitioner for the study. A single investigator performed all interventions. After consent, all adults (18-70 years old) consulting their general practitioner in Paris, France, unaware of their status, were enrolled. Testing was performed immediately for the patients in the rapid test arm; a prescription was given for testing in a lab for the patients in the ELISA arm. The primary endpoint was acceptability of each method. The secondary endpoint was feasibility of each method, assessed one month after the consultation. Results > Two hundred and seventy patients were enrolled: 133 patients in the ELISA arm, 137 in the rapid test arm. Acceptability of the rapid test (92%) was higher than that of the ELISA (63.9%), P < 0.0001. Feasibility of the rapid test (100%) was higher than that of the ELISA (50.5%), P < 0.0001. A center effect was shown concerning feasibility of ELISA but not concerning feasibility of rapid tests. Conclusion > Rapid testing from finger-stick whole blood is more acceptable and feasible than ELISA for routine universal HIV testing. A larger use of rapid tests, ideally free of charge, by general practitioners could reduce the pool of infected patients unaware of their status.

Background The risk of vertical transmission of hepatitis B virus (HBV) increases as maternal HBV DNA increase, despite serovaccination to newborns. Methods From 1 July 2012 to 1 January 2016, all pregnant women in Lariboisiere Hospital, Paris, France, with HBV DNA of 5 log10 IU/ml and above were administered tenofovir from week 28 of pregnancy until delivery. HBV DNA was measured at months 1, 2 of tenofovir and at delivery. The newborns were serovaccinated, tested for hepatitis B surface antigen, hepatitis B core antibody (HBcAb)±HBV DNA, and hepatitis B surface antibody (HBsAb) when aged 9 months, and then 24 months. This study was registered in http://www.ClinicalTrials.gov (NCT02039362). Results Thirty-one women gave birth to 37 newborns. Maternal HBV DNA at baseline was 8.23 log10 IU/ml and above in 12 pregnancies. The mean (median) HBV DNA were 4.4±1.2 (4.8), 3.3±1.7 (3.8), and 2.1±1.9 (2.0) log10 IU/ml at months 1, 2 of tenofovir and at delivery, respectively. Twenty-seven newborns were followed up: none of the 19 children aged 9 months or older was positive for hepatitis B surface antigen when aged 9 months; 14 children tested positive for HBcAb (probably transferred maternal antibodies, not found when aged 24 months) and for HBsAb without HBV DNA. Four of the 19 children showed HBsAb without HBcAb, the last being doubtful for HBcAb and HBsAb without HBV DNA. Eight newborns aged less than 9 months were not tested. Conclusion Tenofovir from week 28 of pregnancy to highly viremic HBV women plus serovaccination to newborns could prevent chronic and past infection.

Hepatitis B Virus (HBV) DNA during chronic infection can reach levels at which mother‐to‐child (MTC) transmission frequently occurs despite passive‐active immunization of newborns. Hepatitis D Virus (HDV) RNA can reach high levels, we assessed HBV/HDV MTC co‐transmission.

OBJECTIVES:We assessed hepatitis B virus (HBV) status in children born to HIV/HBV coinfected women with large access to antiretroviral therapy.METHODS:All HIV/HBV coinfected pregnant women from 01 January 2000 to 01 January 2012 were included in the retrospective study (NCT02044068). Antiretroviral therapy during pregnancy and injection of HBV immunoglobulin/vaccine to newborns was recorded. We assessed HBV status of children aged at least 2 years.RESULTS:Twenty-one women (35 children) were studied. Twenty-six children (74%) had HBsAb: 22 had received immunoglobulin and 24 had received a complete vaccine (with immunoglobulin in 21 cases); their mothers had been administered lamivudine or tenofovir/emtricitabine during eight and nine pregnancies, respectively. Eight children (23%) were negative for HBsAg, HBsAb, and HBcAb: four (11.5%) had received immunoglobulin and a complete vaccine; in two children, it was not known whether they had received an immunoglobulin injection; in one child, the vaccine was incomplete; and in the last one, it was not known whether he had received immunoglobulin/vaccine. Their mothers had been administered lamivudine or tenofovir/emtricitabine during five and two pregnancies, respectively. No infant has chronic HBV infection (HBsAg) after prenatal mothers' antiretroviral therapy combined with a complete postnatal HBV protection. One child had HBcAb and HBsAb: it was not known whether she had received an immunoglobulin injection; the vaccine was incomplete. The mother had been administered lamivudine during the last trimester of pregnancy.CONCLUSION:Antiretroviral therapy in HBV/HIV coinfected women following current national HBV guidelines may prevent mother-to-child-transmission of HBV. Negativity of surrogate markers of vaccine-induced protection is frequent; large studies on long-term protection are needed.

BACKGROUND & AIMS:Mother-to-child (MTC) hepatitis B virus (HBV) transmission has been mainly studied in Asia. The geographical origins of women and HBV genotypes differ in Europe. The aims were to determine the rate and risk factors of MTC HBV transmission from women with high HBV DNA loads in a maternity hospital in Paris, France.METHODS:Retrospective study of HIV-negative, HBs Ag-positive pregnant women with HBV DNA loads above 5 Log10 I.U/ml who were not given lamivudine or tenofovirDF during pregnancy between 2004 and 2011.RESULTS:Among 11 417 pregnant women, 437 (4%) showed a positive HBs Ag. Among these women, 52 had HBV DNA loads above 5 Log10 I.U/ml: 41, 10 and 1 born in Asia, sub-Saharan Africa and Europe respectively. Among the 52 women, 40 were eligible for the analysis: no antiviral therapy during pregnancy; children over 9 months old. Twenty-eight (70%) women were assessed, corresponding to 41 childbirths. Eleven children (27%) had positive HBs Ag, 14 (34%) had positive HBc and HBs Ab, 16 (39%) had positive HBs Ab only. The risk of having positive HBs Ag, according to maternal HBV DNA loads, was 14% for HBV DNA loads less or equal to 8 Log10 I.U/ml, 42% for HBV DNA loads over 8 Log10 I.U/ml, P = 0.04, but not related to the women's origin, HBV genotype.CONCLUSIONS:This study confirms that serovaccination does not fully protect newborns from MTC HBV transmission, when maternal HBV DNA loads exceed 5 Log10 I.U/ml, regardless of the women's origin or HBV genotype.

INTRODUCTION:Human Immunodeficiency Virus (HIV) Mother-To-Child-Transmission (MTCT) and prevention by combined antiretroviral therapy (cART) have been extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co-infected women and prevention by antiretroviral therapy with dual activity have been poorly studied. The aim of the study was to assess HBV MTCT from HIV/HBV co-infected women in a developed country with a large access to cART. MATERIALS AND METHODS:HIV/HBV co-infected pregnant women attending the Obstetrics Department from 1st January 2000 to 1st January 2012 could be included in the study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status of children at least as old as two years. RESULTS:Forty nine (9.2%) from 530 HIV-infected women followed in the hospital were HIV/HBV co-infected. 34 (69.4%) had given birth to 57 children in the hospital. 13 of these women (22 children) were lost-to-follow-up, 21 women (35 children) could be studied. Twenty six children (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin at birth; 24 had received a complete vaccine schedule during the first six months of life (with immunoglobulin in 21 cases). The women had been given lamivudine or tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%) had received immunoglobulin and a complete vaccine schedule; in two children, immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete; in the last one, data about immunoglobulin and the vaccine schedule were lacking. The women had been given lamivudine or tenofovir/emtricitabine during five and two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last trimester. CONCLUSIONS:Three quarters of the children were protected. HBs Ab were negative in more than a tenth of the children who had received immunoglobulin and a complete vaccine schedule, questioning on long-term protection and underlining the need of control.

OBJECTIVE To report a case of an overweight man with lymph node tuberculosis due to Mycobacterium bovis, a part of the Mycobacterium tuberculosis complex, treated with fixed-dose combination (FDC) chemotherapy. CASE REPORT Following guidelines, according to the patient's weight (92 kg), we prescribed the maximum recommended doses of isoniazid-rifampin-pyrazinamide FDC. It led initially to underdosing, with a poor clinical outcome, justifying increased doses and a complex regimen using separate drugs (isoniazid 600 mg, rifampin 1200 mg, and levofloxacin 1000 mg) to achieve therapeutic drug concentrations and clinical response. DISCUSSION Usually recommended doses of FDC chemotherapies may be inappropriate in overweight patients. We discuss here the different factors that may be involved in poor clinical outcomes, particularly the consequences of excess weight on drug metabolism: drug-drug interaction, FDC use, generic formulation use, intestinal malabsorption, and acetylation profile. CONCLUSIONS Therapeutic drug monitoring in overweight patients may be useful in the clinical setting to help clinicians individualize drug therapeutic regimens and optimize drug response, adherence, and safety.

To the Editors: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect, being present in more than 400 million people worldwide.1 The global distribution of this disorder is similar to that of malaria, lending support to the so-called malaria protection hypothesis. G6PD deficiency is an X-linked genetic defect resulting from mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes. Approximately 140 mutations have been described; most are single base changes, leading to amino acid substitutions. In most areas of high prevalence of G6PD deficiency, several polymorphic alleles are found, but in sub-Saharan Africa (SSA), the variant G6PD A- accounts for approximately 90% of G6PD deficiency.2,3 Of the 33 million people in the world infected with HIV, 22 million live in SSA.4 The HIV epidemic in western Europe is now widely related to the flow of migrants from high-burden countries, mainly SSA. In France, patients coming from this area account for 27% of newly diagnosed HIV infection.5 Exposure to sulfa drugs is frequent in HIV-positive patients, because trimethoprim/sulfamethoxazole is the drug most often used for Pneumocystis jiroveci pneumonia prophylaxis and treatment. Either dapsone/trimethoprim or clindamycin/primaquine is effective in the treatment of mild to moderate P. jiroveci pneumonia, but both regimens are contraindicated in G6PD deficiency. Atovaquone should be used in patients who are deficient in G6PD, but this drug is much too expensive for most patients in SSA.6 Moreover, the treatment of toxoplasmosis of the central nervous system is based on a regimen combining pyrimethamin/sulfadiazine. We studied the prevalence of G6PD deficiency in the cohort of SSA male patients attending the HIV unit and looked retrospectively for hemolytic events when receiving sulfa. METHODS From January 1 to December 31, 2008, all HIV-1-positive male patients coming from SSA attending the department were, after written, informed consent, prospectively tested for G6PD deficiency based on the estimation of enzyme activity by quantitative spectrophotometric analysis of the rate of NADPH production from NADP.1 Pyruvate kinase activity was measured for all G6PD-deficient patients. By analyzing the medical records, we looked retrospectively for hemolytic events, with or without clinical manifestations, when receiving sulfa. The baseline and the end of follow-up were defined, respectively, by the first time the patients attended the department and the time (in 2008) of testing for G6PD deficiency. Hemolysis was classified as certain (anemia, increased bilirubin [without taking simultaneously indinavir or atazanavir], increased lactate dehydrogenase, or increased reticulocytosis, or decreased haptoglobin), possible (two or more biologic abnormalities: anemia, increased bilirubin [with or without taking simultaneously indinavir or atazanavir], increased lactate dehydrogenase, increased reticulocytosis), or very unlikely (no anemia, bilirubin within the normal values, [or increased with taking simultaneously indinavir or atazanavir], and normal lactate dehydrogenase, reticulocytosis, or haptoglobin). The comparison between G6PD-tested and -nontested patients and the comparison between deficient and nondeficient patients was made by the Mann-Whitney U test, except for percentages of AIDS (Fisher exact P value). RESULTS Of all adult HIV-1 patients (1256 patients) from the Internal Medicine Department of Lariboisiere Hospital during the period of January to December 2008, 714 (56.8%) were native of SSA (269 men, 445 women), 471 (38%) were white (383 men, 88 women) (native of western Europe [393], North Africa [78]), 26 (2.1%) were native of South America, 24 (1.9%) of the Caribbean, and 19 (1.5%) of Asia. Of the 293 male patients from SSA or the Caribbean, 190 (64.5%) were tested. The 103 (35.5%) remaining patients were checked in private laboratories, missed their appointments, or were lost to follow-up. None of the 293 patients refused to be tested for G6PD deficiency. The 103 nontested patients did not differ from the 190 tested patients with regard to age at study period (41.9 ± 9.3 years versus 42.1 ± 8.2 years, respectively, P = 0.89), duration of previous follow-up (65.5 ± 55.8 months versus 69.9 ± 42.9 months, respectively, P = 0.08), CD4+ T-cell count at the beginning of follow-up (305 ± 243 109/L versus 303 ± 215 109/L, respectively, P = 0.82), CD4+ T-cell count at study period (433 ± 230 109/L versus 432 ± 205 109/L, respectively, P = 0.93), HIV RNA at the beginning of follow-up (4.3 ± 1.1 log10 copies/mL versus 4.5 ± 1.1 log10 copies/mL, respectively, P = 0.35), lines of antiretroviral therapy during previous follow-up (2.1 ± 2.3 versus 2.1 ± 1.9, respectively, P = 0.27), and patients with AIDS at study period (30.1% versus 24.2%, respectively, P = 0.27), except for HIV RNA at the end of follow-up. which was significantly higher in nontested patients (2.8 ± 1.4 log10 copies/mL versus 2.3 ± 1.1 log10 copies/mL, respectively, P = 0.009). This could reflect poorer adherence to treatment attested by more frequent missing of their appointments, explaining the absence of testing for G6PD deficiency. We identified 27 G6PD-deficient patients, 12.8% of the tested patients. G6PD levels were between 0.1 and 2.3 U/g hemoglobin (normal values, 7-11 U/g hemoglobin) with a mean of 1.2 ± 0.4 and a median of 1.2. Mean age was 45.5 ± 8.9 years (median, 43.0 years; range, 34-63 years). Prevalence of G6PD deficiency was calculated respectively: 2.3% in patients from Cameroon (one of 44), 16.3 % in patients from the Ivory Coast (seven of 43), 14% in patients from the Congo Republic (three of 21), 21.4% in patients from Senegal (three of 14), 7.7 % in patients from Mali (one of 13), and 38.5% in patients from Democratic Republic of the Congo (five of 13). Seventeen of the 27 G6PD deficient patients were exposed to sulfa drugs treatment. Table 1 describes their main clinical and biologic characteristics. Fourteen patients could be assessed for hemolysis based on biologic data. According to the early (during the first week after introduction of sulfa) and late (1 month after introduction of sulfa) evaluations of the biologic parameters, hemolysis was classified as possible in five of the 14 (36%) patients who had previously been challenged by sulfa and whose records were complete, allowing precise analysis. They corresponded to 15 challenges because one patient received TMP-SMX initially and then Pyr-SDZ as treatment for central nervous system toxoplasmosis. Time to occurrence of hemolysis was respectively 11, 15, 20, 34, and 37 days postsulfa. In the other nine patients (64%) who had previously been challenged by sulfa and whose records were complete, corresponding to 10 challenges, hemolysis was very unlikely.TABLE 1: Main Clinical and Biologic Characteristics of Glucose-6-Phosphate Dehydrogenase-Deficient Patients Exposed to Sulfa DrugsBecause a chronic subclinical hemolysis could speed up the course of HIV infection by inducing a permanent, eventually deleterious, activation of the immune system, we then verified that the nondeficient did not differ from deficient patients in any of the following parameters: CD4+ T lymphocytes (432 ± 206 versus 436 ± 199/mm3, P = 0.93) and HIV RNA (4.2 ± 4.9 versus 3.4 ± 4.0 log10/mL, P = 0.39) at the end of follow-up. G6PD-deficient patients were followed up for a significantly longer duration (91 ± 42.6 months versus 66.3 ± 42 months, P = 0.002) and were given more lines of antiretroviral treatment than nondeficient patients (mean 3.0 ± 2.5 versus 2.0 ± 1.8, P = 0.028, Mann-Whitney). Despite we were unable to support the hypothesis of permanent smoldering but deleterious inflammation (by measurements of C-reactive protein, d-dimers, or interleukin-6, for instance) in this retrospective study, it could not be ruled out. DISCUSSION We identified 12.8% of sub-Saharan HIV male patients with G6PD deficiency, in accordance with the high prevalence of this deficiency previously reported in SSA populations.7 Among the very different clinical phenotypes observed, according to functional variant and residual biochemical activity in red blood cell, the World Health Organization Class III G6PD A-(202A376G) is the most common African mutation.3 The 27 G6PD-deficient patients identified were probably A because of their sub-Saharan origin and of their residual enzyme activity of 10% to 40%.3 Among the drugs commonly used for prophylaxis or treatment of opportunistic infections in HIV-infected patients, several are contraindicated (sulfadiazin, sulfamethoxazole, trimethoprim); pyrimethamin alone does not seem to lead to hemolytic anemia.8 We used a retrospective design for this study, because a prospective design (giving trimethoprim/sulfamethoxazole as primary prophylaxis in HIV-infected patients previously identified as G6PD-deficient) seemed to us unethical. Hemolytic anemia in G6PD A is self-limiting because only the older red blood cells are destroyed and young red blood cells have normal or near-normal enzyme activity. Our results-no acute clinical hemolysis despite severe deficiency with residual enzyme activity-found at least once at less than 1 U/g hemoglobin in 12 of 27 (44%) patients and lack of chronic subclinical hemolysis in most patients continuing to take sulfa were in accordance with relative contraindications of these drugs.8 In conclusion, systematic screening for G6PD deficiency in sub-Saharan HIV male patients does not seem very useful particularly in developing countries where alternative prophylaxis is not available as a result of its cost. However, G6PD deficiency screening could be useful in the Mediterranean region where G6PD variants are World Health Organization Class II and may be sensitive to drugs where those with milder defects (such as G6PD A-) are not. ACKNOWLEDGMENTS We thank F. Galacteros, MD, PhD (Hôpital Henri Mondor, Créteil, France) for reading of the manuscript. N.M. was responsible for testing for G6PD deficiency; P.C. was responsible for laboratory testing. N.M., A.R., A.A., B.C., J.E., and J.F.B. conceived and designed the study and wrote the manuscript. B.C. and J.D.M. collected the data. G.S. was the study statistician. Pierre O. Sellier, MD, PhD*< Nathalie Mario, MD† Agathe Rami, MD* Annalisa Andreoli, MD‡ Beda M. Choho, MD* Guy Simoneau, MD* Jean-Dominique Magnier* John Evans, MD§ Philippe Chappuis, MD, PhD¶ Jean-François Bergmann, MD, PhD* *Department of Internal Medicine and Infectious Diseases, Lariboisière Hospital, Paris, France †Department of Biochemistry A Saint-Antoine Hospital, Paris, France ‡Department of Clinical Haematology, Lariboisière Hospital, Paris, France §SCOR, Paris la Défense, France ¶Department of Biochemistry, Lariboisière Hospital, Paris, France

Increases in aminotransferases levels are frequently encountered in HIV-positive patients and often remain unexplained. The role in this setting and natural history of hepatitis E in HIV-infected patients are unknown. The aim of the study was to assess HEV infection in HIV-infected patients attending a Parisian hospital, with a current or previous cryptogenic hepatitis.191 plasma samples collected from 108 HIV-infected patients with elevated aminotransferases levels were retrospectively tested for the presence of hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index and plasma HEV RNA.One acute infection, documented by positive tests for anti-HEV IgM antibody, low anti-HEV IgG avidity index and plasma HEV RNA (genotype 3e), and three past infections were diagnosed, without any observed case of persistent infection. The acute hepatitis was benign and resolved spontaneously within two weeks. This infection was probably contracted locally. Acute HEV hepatitis can occur in HIV-infected patients but rarely explains cryptogenic hepatitis, at least in an urban HIV population, regardless geographic origin and CD4 counts.

The sickle cell trait-asymptomatic carriage is frequent in people originating from sub-Saharan Africa. Several host factors (including sickle cell anemia) have been previously reported to act upon the course of HIV disease. We studied the progression of infection in a cohort of African patients heterozygous for the sickle hemoglobin gene and harboring normal hemoglobin genes. No significant difference was evidenced between the two groups from this preliminary study.

Patients with human immunodeficiency virus (HIV) infection who were native to sub-Saharan Africa but lived in France were less adherent to antiretroviral therapy during a visit back to Africa, compared with their level of adherence in France. This was mainly related to self-perceived insufficient support from family members and/or fear of the consequences of disclosure of their HIV infection status to their family.

(2004). Fatal Interruption of a 3TC-containing Regimen in a HIV-infected Patient Due to Re-activation of Chronic Hepatitis B Virus Infection. Scandinavian Journal of Infectious Diseases: Vol. 36, No. 6-7, pp. 533-535.