Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller.

HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural HIV-1 control in individuals off antiretroviral therapy (ART). Here, we describe a bNAb B cell lineage elicited in a post-treatment controller (PTC) that exhibits broad seroneutralization and show that a representative antibody from this lineage, EPTC112, targets a quaternary epitope in the glycan-V3 loop supersite of the HIV-1 envelope glycoprotein. The cryo-EM structure of EPTC112 complexed with soluble BG505 SOSIP.664 envelope trimers revealed interactions with N301- and N156-branched N-glycans and the 324GDIR327 V3 loop motif. Although the sole contemporaneous virus circulating in this PTC was resistant to EPTC112, it was potently neutralized by autologous plasma IgG antibodies. Our findings illuminate how cross-neutralizing antibodies can alter the HIV-1 infection course in PTCs and may control viremia off-ART, supporting their role in functional HIV-1 cure strategies.

Persistently elevated alkaline phosphatase could be related to Paget's disease of bone in a patient receiving tenofovir disoproxil fumarate.

The prevalence of Paget's disease of bone (PDB) reaches 1-2% of all adults aged ≥55 years old. However, reports describing PDB among HIV positive patients are extremely rare. We report here the case of a HIV positive person receiving tenofovir disoproxil fumarate (DF)-based antiretroviral therapy and who had persistently elevated alkaline phosphatase (AP) revealing PDB. It is well established that tenofovir-DF use is associated with reversible increases in serum AP levels. Clinicians should bear in mind that persistently elevated AP in a person receiving tenofovir DF-based cART could be related to PDB, in particular in person older than 50 years with no other notable biological abnormalities related to kidney tubular dysfunction.

Single-Dose 13-Valent Conjugate Pneumococcal Vaccine in People Living With HIV - Immunological Response and Protection.

Background: Patients living with HIV (PLHIV) are prone to invasive pneumococcal disease. The 13-valent conjugated pneumococcal vaccine (PCV13) is currently recommended for all PLHIV, followed in most guidelines by a 23-valent polysaccharide pneumococcal vaccine. Data are scarce concerning the immunological efficacy of PCV13 among PLHIV. Objective: To assess the immunological response at one month, and the immunological protection at 1-, 6-, and 12 months in PLHIV with a CD4 cell count above 200 cells/µl after a single dose of PCV13, as measured by both ELISA and opsonophagocytic assay (OPA). Methods: PLHIV with CD4 cell count >200 cells/µl were included. Specific IgG serum concentrations for eight serotypes by ELISA and seven serotypes by OPA were measured at baseline, 1-, 6-, and 12 months after the PCV13 vaccination. Global response was defined as a two-fold increase from baseline of specific IgG antibody levels (µg/ml) assayed by ELISA or as a four-fold increase in OPA titer from baseline, for at least five serotypes targeted by PCV13. Global protection was defined as an IgG-concentration ≥1 µg/ml by ELISA or as an opsonization titer ≥LLOQ by OPA for at least five tested serotypes targeted by PCV13. Factors associated with global response and global protection were assessed using logistic regression. Results: Of the 38 PLHIV included, 57.9% and 63.2% were global responders, 92.1% and 78.9% were globally protected at one month, and 64.7% and 55.9% were still protected at 12 months, by ELISA and OPA respectively. A CD4/CD8 ratio of >0.8 was significantly associated with a better global response by OPA (OR=6.11, p=0.02), and a CD4 nadir <200 was significantly associated with a poorer global response by ELISA (OR=0.22, p=0.04). A CD4 cell count nadir <200 and age over 50 years were associated with poorer global protection by OPA at M1 (OR=0.18, p=0.04) and M12 (OR= 0.15, p=0.02), respectively. Plasma HIV RNA viral load <40 copies/ml was significantly associated with a better global protection at M1 by ELISA and OPA (OR=21.33, p=0.025 and OR=8.40, p=0.04). Conclusion: Vaccination with PCV13 in these patients induced immunological response and protection at one month. At one year, more than half of patients were still immunologically protected.

Factors Associated with Geophagy and Knowledge About Its Harmful Effects Among Native Sub-Saharan African, Caribbean and French Guiana HIV Patients Living in Northern France.

Geophagy, or the ingestion of earth or clay, is widespread among women of Sub-Saharan African, Caribbean or French Guiana origin. Little is known about this practice among HIV patients native of these countries and who are followed-up in France. The aims of this study were to determine (i) the prevalence and factors associated with geophagy among HIV patients native of these countries, (ii) patients' knowledge about the harmful effects of geophagy, and (iii) the association of geophagy with iron deficiency, or a history of anemia or constipation. Among the 119 included patients, current geophagy and previous geophagy were present in 11/119 (9%) and 47/119 (40%) patients, respectively. Female gender was the only factor associated with consumption (OR 5.37; 95% CI 2.07-15.92 p = 0.001). Awareness about the risk of iron-deficient anemia was low (24%). Preventive education should be integrated into the care of HIV adults from countries in which geophagy is a culture and widely accepted practice.

Early neuropsychological adverse events after switching from PI/r to dolutegravir could be related to hyperthyroidism in patients under levothyroxine.

We report two patients who had taken levothyroxine at the same dose for several years and who had stable thyroid stimulating hormone (TSH) levels, and who developed clinical and biological hyperthyroidism following switch from ritonavir-boosted protease inhibitors (PIs) to dolutegravir-based HAART. Levothyroxine is metabolized by deiodination and glucuronidation and the induction of glucuronidation by ritonavir leads to an increased elimination of levothyroxine and a necessity of higher daily doses. Patients who switch from ritonavir-boosted PIs to antiretroviral drugs-based HAART with minimal drug-interaction such as dolutegravir, may require an adjustment in their dose of levothyroxine in order to prevent hyperthyroidism due to impaired elimination of levothyroxine without ritonavir.

Trends in survival after cancer diagnosis among HIV-infected individuals between 1992 and 2009. Results from the FHDH-ANRS CO4 cohort.

Although the decline in cancer mortality rates with the advent of combination antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained by a decrease in cancers incidence, we looked here if improved survival after cancer diagnosis could also contribute to this decline. Survival trends were analyzed for most frequent cancers in the HIV-infected population followed in the French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year Kaplan-Meier survival rates were estimated for four periods: 1992-1996, 1997-2000, 2001-2004 and 2005-2009. Cox proportional hazard models were used to compare survival across the periods, after adjustment for confounding factors. For 2001-2004, survival was compared to the general population after standardization on age and sex. Between the pre-cART (1992-1996) and early-cART (1997-2000) periods, survival improved after KS, NHL, HL and anal cancer and remained stable after lung and liver cancers. During the cART era, 5-year survival improved after visceral and non-visceral KS, NHL, HL and liver cancer, being 83, 92, 65, 87 and 19% in 2005-2009, respectively, and remained stable after lung and anal cancers, being 16 and 65%, respectively. Compared with the general population, survival in HIV-infected individuals in 2001-2004 was poorer for hematological malignancies and similar for solid tumors. For hematological malignancies, survival continues to improve after 2004, suggesting that the gap between the HIV-infected and general populations will close in the future.

High prevalence of measles seronegativity in adults with HIV infection born in the era of measles vaccination in Northern France.

We investigated measles humoral immunity levels in a cohort of HIV-infected adult patients in France and attempted to identify risk factors for antimeasles antibodies seronegativity. Being born after 1983 [odds ratio (OR) 4.40; 95% confidence interval (95% CI) 1.26-14.09; P = 0.0013] and a nadir CD4⁺ cell count below 100 cells/µl (OR 4.79; 95% CI 1.61-14.82; P = 0.0048) were the two factors independently associated with measles seronegativity. Systematic measles antibody screening should be performed in HIV-infected individuals born in the era of measles vaccination (after 1983 in France).

Laparoscopic entry techniques in obese patient: veress needle, direct trocar insertion or open entry technique?

Laparoscopy is a common procedure in bariatric surgery. Serious complications can occur during laparoscopic entry as reported by Ahmad et al. (Cochrane Database Syst Rev 15:2, 2012). Several techniques, instruments, and approaches to minimize the risk of injury (the bowel, bladder, major abdominal vessels, and an anterior abdominal wall vessel) have been introduced. These methods include the standard technique of insufflation after insertion of the Veress needle, the open (Hasson technique), the direct trocar insertion, and optical trocar insertion. Furthermore, it is more difficult to perform in the obese patient, especially if the first trocar is not umbilical. This is because obese patients have a very thick abdominal wall (particularly in women) as well as a thick peritoneum. The aim of this article was to demonstrate the safety of various laparoscopic entry techniques in obese patient.

Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: results from a French cohort.

OBJECTIVES: Improved survival among HIV-infected individuals after the advent of combination antiretroviral therapy (cART) had drawn attention on non-AIDS-defining cancers. We evaluated the incidence and risk trends of lung cancer, Hodgkin's lymphoma, liver and anal cancers, focusing on patients with CD4 cell recovery and age at diagnosis, by comparison with the general population. DESIGN: Cohort study. METHODS: Standardized incidence rates were calculated in the HIV-infected individuals followed in the FHDH and the general population in France in 1997-2000, 2001-2004, and 2005-2009. We estimated standardized incidence ratios for each period and for patients with CD4 cell count at least 500 cells/µl for at least 2 years on cART. RESULTS: Among the 84,504 HIV-infected individuals, the risk of lung and anal cancers fell during the cART era, whereas that of Hodgkin's lymphoma and liver cancer remained stable. In 2005-2009, the standardized incidence ratios for lung cancer, Hodgkin's lymphoma, liver and anal cancers were, respectively, 2.8 [95% confidence interval (CI) 2.5-3.1], 26.5 (95% CI 23.2-30.1), 10.9 (95% CI 9.6-12.3) and 79.3 (95% CI 69.5-90.1). Among patients with CD4 cell recovery on cART, the risk was close to that of the general population for lung cancer, nine-fold higher for Hodgkin's lymphoma, and 2.4-fold higher for liver cancer. Age at diagnosis was significantly younger among HIV-infected individuals for lung cancer (-3.3 years), Hodgkin's lymphoma (-1 year) and liver cancer (-10.1 years). CONCLUSION: HIV-infected patients were at a higher risk for the four cancers over 1997-2009. CD4 cell recovery appears to control the excess risk of lung cancer. For liver cancer and Hodgkin's lymphoma, our results suggest that CD4 should never drop below 500/µl 500 cells/µl to avoid the excess risk.

Risk of AIDS-defining cancers among HIV-1-infected patients in France between 1992 and 2009: results from the FHDH-ANRS CO4 cohort.

BACKGROUND: We examined trends in the incidence of the 3 AIDS-defining cancers (ADCs; Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL], and cervical cancer) among human immunodeficiency virus (HIV)-infected patients relative to the general population between 1992 and 2009 in France, focusing on age at ADC diagnosis and on patients with controlled viral load and restored immunity on combination antiretroviral therapy (cART). METHODS: Age- and sex-standardized incidence rates were estimated in patients enrolled in the French hospital database on HIV, and in the general population in France during 4 calendar periods (1992-1996, 1997-2000, 2001-2004, and 2005-2009). Standardized incidence ratios (SIRs) were calculated for all periods and separately for patients on cART, with CD4 counts ≥500 cells/µL for at least 2 years and viral load ≤500 copies/mL. RESULTS: Although the incidence of ADCs fell significantly across the calendar periods, the risk remained constantly higher in HIV-infected patients than in the general population. In patients with restored immunity, the relative risk remained significantly elevated for KS (SIR = 35.4; 95% confidence interval [CI], 18.3-61.9), and was similar to that of the general population for NHL (SIR = 1.0; 95% CI, .4-1.8). ADCs were diagnosed at a younger age in HIV-infected patients, with a particularly marked difference for NHL (-11.3 years, P < .0001). CONCLUSIONS: The incidence of all ADCs continued to fall, including cervical cancer, in the cART period, but the risk remained higher than in the general population in 2005-2009. In patients with stably restored immunity, KS remained significantly more frequent than in the general population.

Osteonecrosis in six HIV-infected patients receiving highly active antiretroviral therapy.

OBJECTIVE: To report 6 cases of osteonecrosis in HIV-infected patients treated with highly active antiretroviral therapy (HAART) and compare the observed risk factors with those of published cases. CASE SUMMARIES: Osteonecrosis was diagnosed between 1999 and 2002 in 6 of 417 HIV-infected patients in our department of infectious diseases. At the time of diagnosis, mean patient age was 42 years, and 5 patients had developed AIDS. Mean CD4+ lymphocyte count was 563.5 cells/mm(3) and viral load was undetectable (<50 copies/mL) in 5 patients. The patients' mean body mass index was 22.5 kg/m(2). Four had lipodystrophy. All were receiving HAART, including a protease inhibitor in 4 patients; the remaining 2 patients had a history of protease inhibitor treatment. Median time from the first antiretroviral therapy to osteonecrosis diagnosis was 46.5 months. Established risk factors were the use of corticosteroids in 2 patients and dyslipidemia in all patients. All of the patients developed pain and functional impotence of the hip or ankle joints. Osteonecrosis of the hip was bilateral in 4 cases. Three patients required surgical intervention, all of whom had favorable outcomes. DISCUSSION: HIV-infected patients are at a higher risk for the development of osteonecrosis and are more likely to be exposed to predisposing factors to its development. The HAART implication as a predisposing factor remains controversial. CONCLUSIONS: The pathogenesis of osteonecrosis in HIV-infected individuals may be multifactorial; the reasonable approach for clinicians consists of treating concomitant predisposing conditions that might further cause osteonecrosis.