Superinfection by Discordant Subtypes of HIV-1 Does Not Enhance the Neutralizing Antibody Response against Autologous Virus

Recent studies have demonstrated that both the potency and breadth of the humoral anti-HIV-1 immune response in generating neutralizing antibodies (nAbs) against heterologous viruses are significantly enhanced after superinfection by discordant HIV-1 subtypes, suggesting that repeated exposure of the immune system to highly diverse HIV-1 antigens can significantly improve anti-HIV-1 immunity. Thus, we investigated whether sequential plasma from these subjects superinfected with discordant HIV-1 subtypes, who exhibit broad nAbs against heterologous viruses, also neutralize their discordant early autologous viruses with increasing potency. Comparing the neutralization capacities of sequential plasma obtained before and after superinfection of 4 subjects to those of matched plasma obtained from 4 singly infected control subjects, no difference in the increase in neutralization capacity was observed between the two groups (p = 0.328). Overall, a higher increase in neutralization over time was detected in the singly infected patients (mean change in IC50 titer from first to last plasma sample: 183.4) compared to the superinfected study subjects (mean change in IC50 titer from first to last plasma sample: 66.5). Analysis of the Breadth-Potency Scores confirmed that there was no significant difference in the increase in superinfected and singly infected study subjects (p = 0.234). These studies suggest that while superinfection by discordant subtypes induces antibodies with enhanced neutralizing breadth and potency against heterologous viruses, the potency to neutralize their autologous viruses is not better than those seen in singly infected patients

Comparison of mean IC₅₀ titers of superinfected and singly infected study subjects against heterologous and autologous viruses.

<p>IC₅₀ titers against heterologous viruses were taken from the following publication: Powell, R. L., T. Kinge, and P. N. Nyambi. 2010. Infection by discordant strains of HIV-1 markedly enhances the neutralizing antibody response against heterologous virus.</p

Neutralization of autologous virus variants by serially-diluted plasma obtained from singly infected patients.

<p>Mean IC₅₀ values with standard deviation of A: study subject CMNYU133. B: study subject CMNYU179. C: study subject CMNYU153. D: study subject CMNYU6542.</p

Neutralization of autologous virus variants by serially-diluted plasma obtained from study subject CMNYU129.

<p>A: Mean IC₅₀ values with standard deviation of initial and superinfecting virus variants. B: Titration of last plasma against initial (mean of initial variants in red) and successive virus variants (mean of successive variants in blue). Only variants that reached 50% neutralization are included.</p

Phylogenetic analysis of <i>gp120</i> sequences (HXB2 location 6219–7787) amplified from patient plasma samples and used to construct pseudotyped viruses.

<p>Most reference and study subject sequences have been omitted for clarity. Reference sequences are highlighted by black circles.</p

Data of HIV-1 viruses infecting study subjects.

<p>Data of HIV-1 viruses infecting study subjects.</p

Neutralization of autologous virus variants by serially-diluted plasma obtained from study subject CMNYU6544.

<p>A: Mean IC₅₀ values with standard deviation of initial and superinfecting virus variants. B: Titration of last plasma against initial (mean of initial variants in red) and successive virus variants (mean of successive variants in blue). Only variants that reached 50% neutralization are included.</p

Neutralization of autologous virus variants by serially-diluted plasma obtained from study subject CMNYU107.

<p>A: Mean IC₅₀ values with standard deviation of initial and superinfecting virus variants. B: Titration of last plasma against initial (mean of initial variants in red) and successive virus variants (mean of successive variants in blue). Only variants that reached 50% neutralization are included.</p

Rates of HBV, HCV, HDV and HIV type 1 among pregnant women and HIV type 1 drug resistance-associated mutations in breastfeeding women on antiretroviral therapy

Abstract Background HBV, HCV, HDV and HIV are blood borne and can be transmitted from mother-to-child. Reports of HBV infection rates show up to 11.9% in Cameroon while for HCV, the rate is less than 2%. More so, as pregnant women get enrolled in the HIV PMTCT Programme and stay in the care continuum, selection of HIV-1 drug resistant strains is evident. We sought to determine the seroprevalence of HBV, HCV, HDV and HIV among pregnant women, assess their knowledge, attitudes and practices on transmission and prevention of HBV infection, and determine HIV drug resistance profile of breastfeeding women. Methods A serosurvey of HBV, HCV, HDV and HIV was carried out among 1005 pregnant women in Yaounde, Cameroon. In 40 HIV-infected breastfeeding women enrolled in the PMTCT Programme, HIV-1 genotypes and HIV-1 resistance to NRTIs, NNRTIs and PIs, were determined by phylogeny and the Stanford University HIV Drug Resistance interpretation tool, respectively. Results Among the pregnant women, the rates of HIV-1, HBV, HCV and HDV infections were 8.5, 6.4, 0.8 and 4.0%, respectively. About 5.9% of the women knew their HBV status before pregnancy unlike 63.7% who knew their HIV status. Although 83.3% reported that vaccination against HBV infection is a method of prevention, and 47.1% knew that HBV could be transmitted from mother-to-child, only 2.5% had received the Hepatitis B vaccine. Of the 40 women on antiretroviral therapy (ART), 9 had at least one major resistance-associated mutation (RAM, 22.5%) to NRTI, NNRTI or PI. Of these M184 V (12.5%), K70R (10.0%), K103 N (12.5%), Y181C (10.0%), M46 L (2.5%) and L90 M (2.5%) were most frequently identified, suggesting resistance to lamivudine, nevirapine, efavirenz and zidovudine. Eighty four percent were infected with HIV-1 recombinant strains with CRF02_AG predominating (50%). Conclusions The rates of HBV and HIV-1 infections point to the need for early diagnosis of these viruses during pregnancy and referral to care services in order to minimize the risk of MTCT. Furthermore, our results would be useful for evaluating the HIV PMTCT Programme and Treatment Guidelines for Cameroon

Clinical Versus Echographic Estimation of Fetal Weight at Term in A Selected Caucasian Milieu: A Comparative Analysis of The Kongnyuy – Mbu’s Clinical Estimation

Background: Estimation of fetal weight is essential in contemporary obstetrics. Clinical estimations using maternal and fetal characteristics and ultrasound methods exist. We compared a simple clinical estimation that is in use in low resourced facilities in Cameroon and ultrasound in a completely Caucasian environment. <div>Methodology: In this cross –sectional study, consented pregnant women with singleton pregnancies were carefully selected and enrolled. Those with adjuvant pathologies that increased uterine volumes were eliminated. We measured fundal heights and applied the Kornyuy – Mbu’s formula for birth weights and compared these with echographic estimations and actual birth weights. We calculated the percentage error between estimated birth weights (EBW) and actual birth weights (ABW) for accuracy and the ratio by percentage of estimation within 10% of actual birth weights. Results: The average birth weight was 3,529 + 0.35g. We did not have any baby who weighed <2500g, 89.6% weighed between 2,500 - < 4000g, and 10.4% had BW > 4,000g. The mean maternal age was 29, 2 + 4 years. The median gravidity and parity were 2 and1 respectively. The mean gestational age at delivery was 40.8 + 0.6 weeks. Clinical method underestimated and echographic method overestimated birth weights slightly but with no significance difference (P=0.130). Clinical method was able to estimate birth-weights within 10% of actual birth weight in all the subjects as against only 50% of the subjects with ultrasound. </div><div>Conclusion: Clinical estimation of birth weight as described by Kornyuy and Mbu is as accurate as routine echographic estimation in cases that are well selected.</div