Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co-infected patients from Western Africa.

The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)-infected patients. Whether this mutation affects the therapeutic course of HIV-HBV co-infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)-naïve HIV-HBV co-infected patients from Côte d'Ivoire, initiating ARV-treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV-DNA, hepatitis B "e" antigen (HBeAg) seroclearance (in HBeAg-positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV-initiation, median HBV-DNA was 6.04 log10 copies/mL (IQR = 3.70-7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg-negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24-36). Cumulative proportion of undetectable HBV-DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV-DNA levels and anti-HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti-HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.

CD4+ T-lymphocytes natural decrease in HAART-naïve HIV-infected adults in Abidjan.

OBJECTIVE: To study the CD4 natural decrease and its determinants in sub-Saharan African HIV-infected adults. METHOD: We performed a 7-year prospective cohort study, with biannual CD4 measurement. Follow-up was censored at the first severe morbidity event or at HAART initiation. Changes in CD4 values were studied by jointly modelling (a) the correlation between repeated measures through a linear mixed model and (b) the time to drop-out through a survival model. RESULTS: 690 patients were followed up during 1,382 person-years. Contrasting with the baseline CD4 count and percentage, which were associated with numerous variables, the slopes of both CD4 count and CD4 percentage in the absence of severe morbidity episode were only associated with the follow-up time and with the baseline body mass index (BMI). The mean annual natural decrease in CD4 count (CD4%) was estimated at -81/mm3 (-2.2%), -69/mm3 (-1.7%), and -55/mm3 (-1.2%) for patients with baseline BMI at 16 kg/m2, 20.4 kg/m2, and 25 kg/m2, respectively (p < .001). A steeper decline in the CD4 count was independently associated with a shorter event-free follow-up time. CONCLUSION: These estimates of the CD4 natural decrease in sub-Saharan African patients, while they did not experience any episode of severe morbidity and before they initiate HAART, are in the bracket of those previously reported in industrialized countries. In sub-Saharan African settings with CD4 count being measured less frequently than in industrialized countries, the CD4 should be monitored more closely among adults with low BMI.

Screening for active tuberculosis before isoniazid preventive therapy among HIV-infected West African adults.

SETTING: TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance. OBJECTIVE: To report the frequency of undiagnosed TB in patients enrolled for IPT and describe the results of a 1-month buffer period to avoid prescribing IPT for active TB cases. DESIGN: Patients were screened using a clinical algorithm and chest X-ray at Day 0 and started on isoniazid at Month 1 if no sign/symptom suggestive of TB appeared between Day 0 and Month 1. RESULTS: Of 1030 patients randomised into IPT arms. 10% never started IPT at Month 1. Of these, 23 had active TB, including 16 with prevalent TB. Among the 927 patients who started IPT, 6 had active TB, including 1 with prevalent TB. Only 1 patient with active TB received IPT due to the 1-month buffer period between Day 0 and IPT initiation. CONCLUSION: In this study, 1.6% of adults considered free of active TB based on clinical screening at pre-inclusion actually had active TB.

Isoelectric focusing in immobilized pH gradient of melon (Cucumis melo L.) seed protein: methodical and genetic aspects, and application in breeding.

Genetic variability of melon seed proteins was studied by separation of seed protein by isoelectric focusing in immobilized pH gradient (IEF-IPG) under denaturing conditions. A routine procedure was developed for IEF-IPG of hundreds of individual melon seeds per day. A group of 74 accessions from 19 morphologically distinct groups and from different geographic origin were studied by IEF-IPG using pH gradients of 4-10, 4-7 and 6-10. The electrophoretic analysis of the 74 accessions showed 270 reproducible seed protein bands of which 70 were variable. Genetic evaluation led to the conclusion that at least 20 loci govern the variation found. The phylogenetic trees constructed using the protein data on one hand and the morphological data on the other hand were compared and their use was evaluated. A number of commercial Cantaloup F1 hybrid descendants derived from the F1 hybrids by diplohaploidization or single plot descent were studied by IEF-IPG using pH gradients of 4-7 and 6-10. Among the F1 hybrids and their descendants 265 reproducible protein bands could be identified of which 72 were variable as to presence versus absence. The genetic interpretation of the protein pattern as found by IEF-IPG and the use of IEF-IPG in plant breeding was discussed. It was concluded that IEP-IPG of melon seed proteins is a valuable tool in breeding.