High Prevalence of Severe Food Insecurity and Malnutrition among HIV-Infected Adults in Senegal,West Africa

Background

Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes.

Methods

We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review.

Results

One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01).

Conclusions

Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population.     

Pharmacological Actions of Hydrogen Sulfide Donors on Sympathetic Neurotransmission in the Bovine Anterior Uvea,In Vitro

In the present study, we investigated the effect of three different sources of hydrogen sulfide (H₂S) on sympathetic neurotransmission from isolated superfused bovine iris-ciliary bodies. The three agents under consideration were: ACS67, a hybrid of latanoprost and a H₂S-donating moiety; l-cysteine, a substrate for endogenous production of H₂S and GYY 4137, a slow donor of H₂S. We also examined the contribution of prostaglandins to the pharmacological actions of the H₂S donors on release of [³H]-norepinephrine ([³H]NE) triggered by electrical field stimulation. ACS67, l-cysteine and GYY 4137 caused a concentration-dependent inhibition of electrically-evoked [³H]NE release from isolated bovine iris-ciliary bodies without affecting basal [³H]NE efflux. The cyclooxygenase inhibitor, flurbiprofen enhanced the inhibitory action of ACS67 and l-cysteine on stimulated [³H]NE release. Both aminooxyacetic acid, an inhibitor of cystathionine-β-synthase and glibenclamide, a K_ATP channel blocker reversed the inhibition of evoked NE release induced by the H₂S donors. We conclude that H₂S donors can inhibit sympathetic neurotransmission from isolated bovine iris-ciliary bodies, an effect partially dependent on the in situ production of H₂S and prostanoids, and is mediated by an action on K_ATP channels.     

HIV-2 Integrase Variation in Integrase Inhibitor-Na?ve Adults in Senegal,West Africa

Background

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Methods

We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.

Results

No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.

Conclusion

Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients.     

Sensitivity of IFN-γ Release Assay to Detect Latent Tuberculosis Infection Is Retained in HIV-Infected Patients but Dependent on HIV/AIDS Progression

Background

Detection and treatment of latent TB infection (LTBI) in HIV infected individuals is strongly recommended to decrease morbidity and mortality in countries with high levels of HIV.

Objective

To assess the validity of a newly developed in-house ELISPOT interferon-γ release assay (IGRA) for the detection of LTBI amongst HIV infected individuals, in comparison with the Tuberculin Skin Test (TST).

Methodology/Principal Findings

ESAT6/CFP10 (EC) ELISPOT assays were performed, together with a TST, in 285 HIV infected individuals recruited in HIV clinics in Dakar, Senegal, who had no signs of active TB at time of enrolment. Thirty eight of the subjects (13.3%) failed to respond to PHA stimulation and were excluded from the analysis. In the 247 remaining patients, response to PHA did not vary according to CD4 cell count categories (p = 0.51). EC ELISPOT was positive in 125 (50.6%) subjects, while 53 (21.5%) had a positive TST. Concordance between EC ELISPOT and TST was observed in 151 patients (61.1%) (kappa = 0.23). The proportion of subjects with a positive response to the EC ELISPOT assay decreased with declining CD4 counts (p trend = 0.001), but were consistently higher than the proportion of TST responders. In multivariate analysis, the risk of being EC-ELISPOT positive in HIV infected individuals was associated with age, CD4 count and HIV-1 strain.

Conclusion

Our study indicates that IGRAs using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals, but may be impaired by T-cell anergy in severely immuno-suppressed individuals.     

Regulation of [<Superscript>3</Superscript>H] <Emphasis Type="SmallCaps">d</Emphasis>-Aspartate Release from Mammalian Isolated Retinae by Hydrogen Sulfide

Hydrogen sulfide (H₂S), can produce pharmacological effects on neural and non-neural tissues from several mammalian species. The present study investigates the pharmacological action of H₂S, (using sodium hydrosulfide, NaHS, and/or sodium sulfide, Na₂S as donors) on amino acid neurotransmission (using [³H] d-aspartate as a marker for glutamate) from isolated, superfused bovine and porcine retinae. Isolated neural retinae were incubated in Krebs solution containing [³H] d-aspartate at 37°C. Release of [³H] d-aspartate was elicited by high potassium (K⁺ 50 mM) pulse. Both NaHS and Na₂S donors caused an inhibition of K⁺-evoked [³H] d-aspartate release from isolated bovine retinae without affecting basal [³H] d-aspartate efflux yielding IC₅₀ values of 0.006 and 6 μm, respectively. Furthermore, NaHS inhibited depolarization-evoked release of [³H] d-aspartate from isolated porcine retinae with an IC₅₀ value of 8 μM. The inhibitory action of NaHS on [³H] d-aspartate release from porcine retinae was blocked by propargyglycine, a selective inhibitor of cystathionine γ-lyase (CSE). Our results indicate that H₂S donors can inhibit amino acid neurotransmission from both isolated bovine and porcine retinae, an effect that is dependent, at least in part, on intramural biosynthesis of H₂S.     

Two Doses of Candidate TB Vaccine MVA85A in Antiretroviral Therapy (ART) Na?ve Subjects Gives Comparable Immunogenicity to One Dose in ART+ Subjects

Tuberculosis (TB) is a global public health problem exacerbated by the HIV epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in HIV-infected adults in Senegal. 24 patients were enrolled: Group 1∶12, antiretroviral therapy (ART) naïve, adults, with CD4 counts >300 and HIV RNA load <100 000 copies/ml. Group 2∶12 adults, stable on ART, with CD4 counts >300, and an undetectable HIV RNA load. Safety was evaluated by occurrence of local and systemic adverse events (AEs) and by monitoring of CD4 count, HIV RNA load, haematology and biochemistry. Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay. 87.7% of AEs were mild; 11.6% were moderate; and 0.7% were severe. 29.2% of AEs were systemic; 70.8% were expected local AEs. There were no vaccine-related Serious Adverse Events (SAEs) or clinically significant effects on HIV RNA load or CD4 count. In ART naive subjects, the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation, which contracted to baseline by 12 weeks. Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination. A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects. Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects; responses were comparable after 2 immunisations. In conclusion, MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal. A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART.Clinicaltrials.gov trial identifier {"type":"clinical-trial","attrs":{"text":"NCT00731471","term_id":"NCT00731471"}}NCT00731471.     

Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load

Background and Aims

Despite the high prevalence of chronic hepatitis B (CHB) in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM) and two biochemical scores (FibroTest®, Fibrometer®) to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log₁₀ IU/mL and normal alanine aminotransferase (ALT) values.

Methods

LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB). Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring.

Results

225 patients were evaluated (84% male) and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7–13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT), and Fibrometer® (FM) using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis) and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively.

Conclusion

In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.     

Endogenous production of hydrogen sulfide in isolated bovine eye

Hydrogen sulfide (H₂S) is a novel gasotransmitter with physiological and pathological functions in vascular homeostasis, cardiovascular system and central nervous system. In the present study, we determined the endogenous levels of H₂S in various tissues of the bovine eye. We also examined the basal levels of H₂S in response to donors (sodium hydrosulfide, NaHS and sodium sulfide, Na₂S), substrate (l-cysteine), inhibitors (propargylglycine, PAG and aminooxyacetic acid, AOA) and activator (S-adenosyl-l-methionine, SAM) of this gas in the bovine retina. H₂S was measured using a well established spectrophotometric method. The highest concentration of endogenous H₂S was detected in cornea (19 ± 2.85 nmoles/mg protein, n = 6) and retina (17 ± 2.1 nmoles/mg protein, n = 6). Interestingly, H₂S was not present in vitreous humor. The inhibitors of CSE and CBS; PAG (1 mM) and AOA (1 mM), significantly attenuated the production of H₂S in the bovine retina by 56.8 and 42%, respectively. On the other hand the activator of CBS; SAM (100 μM), H₂S donors; NaHS (1 μM) and Na₂S (100 μM), significantly increased endogenous levels of H₂S in bovine retina. l-cysteine (10–300 μM) produced a significant (P < 0.05) concentration-dependent increase in H₂S levels reaching a maximal at 300 μM. We conclude that H₂S is endogenously produced in various tissues of the isolated bovine eye. Moreover, endogenous levels of H₂S are enhanced in the presence of substrate (l-cysteine), an activator of CBS (SAM) and H₂S donors but are blocked by inhibitors of enzymes that synthesize this gas in neural retina.