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Background: The determination of IgG levels and their subclasses can provide clinically relevant information on the status of the immune system. Here we determined the sensitivity and reproducibility of the quantification of IgG subclasses from Dried Blood Spots (DBS) in Malawian uninfected infants exposed to HIV (HEU)., Methods: Sixty paired samples of serum and DBS from HEU infants were used. Samples were collected from 1, 6, and 24-month old infants. IgGs concentrations from both serum and DBS were analyzed by BN ProSpec Siemens assay, using a different setting for sample dilutions. The reproducibility of the DBS method was tested on 10 samples run twice, starting from the DBS extraction process. To assess the systematic, proportional, and random differences, we computed the Passing-Bablok regression, and the Bland-Altman analysis to estimate the total mean bias between the two tests., Results: The IgG isotypes concentrations from serum and DBS showed significant differences in all the comparisons. Generally, the DBS method underestimated IgG subclasses' values showing a recovery range between 51.2% and 77.6%. Passing Bablok regression on age-based groups showed agreement for IgG, IgG1, and IgG2, but not for IgG3 and IgG4. The mean bias obtained with the Bland Altman test varied largely depending on IgG isotypes (-0.02-2.21 g/l) Coefficient of variation <7.0% was found in the repeated tests for IgG, IgG1, IgG3, and IgG4, while it was 12.4% for IgG2., Conclusions: Varying degrees of differences were seen in the IgGs measurement in the two different matrices. In IgGs analysis, the DBS method offers promise for population-based research, but the results should be carefully evaluated and considered as a relative value since they are not equivalent to the serum concentrations., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Hypergammaglobulinemia and anomalies in the IgG subclass distribution are common in HIV-infected individuals and persist even after many years of antiretroviral therapy (ART). The aim of this study was to investigate the IgG profile and dynamics in pregnant HIV-infected Malawian women in the Option B era., Methods: Thirty-seven treatment-naive women received ART from the third trimester of pregnancy to 6 months post delivery (end of the breastfeeding period). ART continuation (group C) or interruption (group I) was then decided on the basis of the CD4+ cell count at enrolment (>350 or ≤350/μl). Total IgG and IgG subclasses were determined in maternal serum using a nephelometric assay at baseline and at 6 and 24 months postpartum., Results: At enrolment, 36/37 women had IgG levels >15g/l and there was a predominance of the IgG1 isotype (more than 90%) in parallel with underrepresentation of IgG2 (5.0%). After 6 months of ART, both groups showed a significant median decrease in total IgG (-3.1g/l in group I, -3.5g/l in group C) and in IgG1 (-4.0g/l and -3.6g/l, respectively), but only a modest recovery in IgG2 levels (+0.16 in group I, +0.14g/l in group C). At month 24, hypergammaglobulinemia was still present in 73.7% of women in group C, although a significant reduction was observed in total IgG level and in IgG1 and IgG3 subclasses (p<0.0001 in all cases). IgG2 levels did not show any significant change. In group I at 24 months, total IgG and IgG subclasses had returned to levels comparable to those at baseline., Conclusions: The beneficial effects of 24 months of ART appear to be limited in the B-cell compartment, with an incomplete reduction of total IgG levels and no recovery of IgG2 depletion. A short ART period did not have significant effects on IgG abnormalities in women who interrupted treatment., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The objective of this study was to determine the prevalence of drug resistance mutations among HIV-positive women in Malawi 18 months after discontinuing nevirapine-based ART for the prevention of mother-to-child transmission., Patients and Methods: HIV-infected antiretroviral-naive (except for single-dose nevirapine) pregnant Malawian women receiving a nevirapine-based triple antiretroviral regimen from Week 25 of gestation until 6 months of breastfeeding were included in this analysis. Drug resistance was assessed in HIV-DNA 24 months post-partum and at baseline (before the initiation of treatment). In patients with resistance, the presence of mutations was also evaluated in the corresponding plasma samples., Results: Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. In four cases, resistance mutations were already present at baseline (all NNRTI mutations). In three cases, there was an emergence of 'new' resistance (also present in the plasma in one case). Of the 35 women without resistance mutations at Month 24, only one subject had resistance mutations at baseline. Baseline resistance was significantly more common among women with mutations at 24 months compared with those harbouring a WT virus (4/7 versus 1/35, P < 0.001)., Conclusions: Among women who had discontinued drugs 6 months post-partum, only 3/42 (7.1%) had accumulated new resistance mutations in HIV-DNA 2 years after delivery. These findings are reassuring in terms of the safety of the Option B strategy for the prevention of HIV mother-to-child transmission., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To identify factors associated with detectable viral load and the emergence of drug resistance in a cohort of HIV-infected pregnant women in Malawi receiving antiretroviral combination regimens for the prevention of mother-to-infant transmission., Methods: The study included 260 treatment-naive women who had received a three-drug nevirapine-based regimen from week 25 of gestational age until 6 months after delivery. HIV RNA was determined at month 6 and drug resistance was assessed if viral load was >50 copies/mL. Attendance at the scheduled follow-up visits was used as an indirect measure of treatment adherence., Results: The rate of detectable HIV RNA at 6 months was 9.6% (25/260). The only significant predictor of this occurrence was the presence of ≥1 missed visit during follow-up (P = 0.012). Resistance was assessed in 19 of these women: 7 (37%) had a wild-type virus and the other 12 (63%) had resistance-associated mutations (nucleoside reverse transcriptase inhibitor, 7/12; non-nucleoside reverse transcriptase inhibitor, 11/12). Three of 12 cases (25%) in which mutations were detected had a viral load <1000 copies/mL. The emergence of resistance was not correlated with the presence of baseline mutations in either plasma or archived DNA., Conclusions: In this cohort of women, detectable HIV RNA 6 months post-partum was infrequent and associated with low adherence to the treatment programme. Mutations were present in 63% of the women with detectable viral load at 6 months who had samples available for resistance testing. The impact of resistance on treatment re-initiation in women discontinuing drugs after the risk of transmission has ceased can be limited.

Background: The administration of antiretroviral therapy to lactating women could represent a possible strategy to reduce postnatal HIV transmission. In this study, we assessed the effect of antiretroviral treatment on breast milk viral load and determined plasma and breast milk drug concentrations in pregnant women receiving highly active antiretroviral therapy (HAART)., Methods: We studied 40 women receiving zidovudine, lamivudine, and nevirapine from 28 weeks of gestation to 1 month postpartum (group A) and 40 untreated pregnant women (group B). Blood and breast milk samples were collected at delivery and 7 days postpartum., Results: Women in group A had received a median of 85 days of therapy before delivery. Median breast milk concentrations of nevirapine, lamivudine, and zidovudine were 0.6, 1.8, and 1.1 times, respectively, those in maternal plasma. HIV RNA levels in breast milk were significantly lower in group A than in group B (median of 2.3 vs. 3.4 log at delivery and 1.9 vs. 3.6 log at day 7; P < 0.001 for both comparisons)., Conclusions: Antiretroviral drugs administered during the last trimester of pregnancy and after delivery reach levels similar to or higher than plasma concentrations in breast milk and can significantly reduce HIV RNA levels. Our data support the potential role of maternal HAART prophylaxis in reducing the risk of breast-feeding-associated transmission.

Objectives Retention of subjects in HIV treatment programmes is crucial for the success of treatment. We evaluated retention/loss to follow-up ( LTFU) in subjects receiving established care in Malawi. Methods Data for HIV-positive patients registered in Drug Resource Enhancement Against AIDS and Malnutrition centres in Malawi prior to 2014 were reviewed. Visits entailing HIV testing/counselling, laboratory evaluations, nutritional evaluation/supplementation, community support, peer education, and antiretroviral ( ART) monitoring/pharmacy were noted. LTFU was defined as > 90 days without an encounter. Parameters potentially associated with LTFU were explored, with univariate/multivariate logistic regression analyses being performed. Results Fifteen thousand and ninety-nine patients registered before 2014; 202 (1.3%) were lost to follow-up ( LTFU) (1.3%). Nine (0.5%) of 1744 paediatric patients were LTFU vs. 1.4% ( n = 193) of 13 355 adults ( P < 0.001). Subjects who were LTFU had fewer days in care than retained subjects (1338 vs. 1544, respectively; P < 0.001) and a longer duration of ART (1530 vs. 1300 days, respectively; P < 0.001). Subjects who were LTFU had higher baseline HIV viral loads ( P = 0.016) and higher body mass indexes ( P < 0.001), were more likely to live in urban settings (88% of patients who were LTFU lived in urban settings) with better housing [relative risk ( RR) 2.3; 95% confidence interval ( CI) 1.67-3.09; P < 0.001], and were more likely to be educated ( RR 1.88; 95% CI 1.42-2.50; P < 0.001). Distance to the centre and cost of transportation were associated with LTFU ( RR 3.4; 95% CI 2.84-5.37; P < 0.001), as was absence of a maternal figure ( RR 1.57; 95% CI 1.17-2.09; P < 0.001). Viral load, distance index, education and a maternal figure were predictive of LTFU. Conclusions Educated, urbanized HIV-infected adults living far from programme centres are at high risk of LTFU, particularly if there is no maternal figure in the household. These variables must be taken into consideration when developing retention strategies. [ABSTRACT FROM AUTHOR]