Resistance mutations in HIV-1 infected pregnant women and their infants receiving antiretrovirals to prevent HIV-1 vertical transmission in China

Introduction Despite being a leading infectious cause of childhood disability globally, testing for cytomegalovirus (CMV) infections in pregnancy is generally not done in Sub-Sahara Africa (SSA), where breastfeeding practice is almost universal. Whilst CMV and human immunodeficiency virus (HIV) are both endemic in SSA, the relationship between antenatal plasma CMV-DNA, HIV-1-RNA levels and HIV-1-mother to child transmission (MTCT) including pregnancy outcomes remains poorly described. Methods Pregnant women at least 20 weeks’ gestational age at enrolment were recruited from relatively poor high-density suburbs in Harare, Zimbabwe. Mother-infant dyads were followed up until 6 months postpartum. In a case–control study design, we tested antenatal plasma CMV-DNA levels in all 11 HIV-1 transmitting mothers, as well as randomly selected HIV-infected but non-transmitting mothers and HIV-uninfected controls. CMV-DNA was detected and quantified using polymerase chain reaction (PCR) technique. Antenatal plasma HIV-1-RNA load was quantified by reverse transcriptase PCR. Infants’ HIV-1 infection was detected using qualitative proviral DNA-PCR. Predictive value of antenatal plasma CMV-DNAemia (CMV-DNA of > 50 copies/mL) for HIV-1-MTCT was analyzed in univariate and multivariate regression analyses. Associations of CMV-DNAemia with HIV-1-RNA levels and pregnancy outcomes were also explored. Results CMV-DNAemia data were available for 11 HIV-1 transmitting mothers, 120 HIV-infected but non-transmitting controls and 46 HIV-uninfected mothers. In a multivariate logistic regression model, we found a significant association between CMV-DNAemia of > 50 copies/mL and HIV-1 vertical transmission (p = 0.035). There was no difference in frequencies of detectable CMV-DNAemia between HIV-infected and -uninfected pregnant women (p = 0.841). However, CMV-DNA levels were higher in immunosuppressed HIV-infected pregnant women, CD4 < 200 cells/µL (p = 0.018). Non-significant associations of more preterm births (< 37 weeks, p = 0.063), and generally lower birth weights (< 2500 g, p = 0.450) were observed in infants born of HIV-infected mothers with CMV-DNAemia. Furthermore, in a multivariate analysis of HIV-infected but non-transmitting mothers, CMV-DNAemia of > 50 copies/mL correlated significantly with antenatal plasma HIV-1-RNA load (p = 0.002). Conclusion Antenatal plasma CMV-DNA of > 50 copies/mL may be an independent risk factor for HIV-1-MTCT and higher plasma HIV-1-RNA load, raising the possibility that controlling antenatal CMV-DNAemia might improve infant health outcomes. Further studies with larger sample sizes are warranted to confirm our findings.

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HIV-1 pol Gene Polymorphism and Antiretroviral Resistance Mutations in Drug-Naive Pregnant Women in Yaoundé, Cameroon

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/01.qai.0000209909.20373.3b ◽

2006 ◽

Vol 42 (2) ◽

pp. 256-258 ◽

Cited By ~ 20

Author(s):

Aurélia Vessière ◽

Eric Nerrienet ◽

Anfumbom Kfutwah ◽

Elisabeth Menu ◽

Mathurin Tejiokem ◽

...

Keyword(s):

Gene Polymorphism ◽

Pregnant Women ◽

Resistance Mutations ◽

Antiretroviral Resistance ◽

Drug Naïve ◽

Hiv 1

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RISK FACTORS OF HIV-1 VERTICAL TRANSMISSION (VT) AND THE INFLUENCE OF ANTIRETROVIRAL THERAPY (ART) IN PREGNANCY OUTCOME

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652014000200008 ◽

2014 ◽

Vol 56 (2) ◽

pp. 133-138 ◽

Cited By ~ 12

Author(s):

Maria F.M. Barral ◽

Gisele R. de Oliveira ◽

Rubens C. Lobato ◽

Raul A. Mendoza-Sassi ◽

Ana M.b. Martínez ◽

...

Keyword(s):

Risk Factors ◽

Prenatal Care ◽

Pregnant Women ◽

Pregnancy Outcome ◽

Vertical Transmission ◽

First Trimester ◽

Antiretroviral Drugs ◽

Vertical Transmission Of Hiv ◽

Hiv 1 ◽

In Pregnancy

In the absence of intervention, the rate of vertical transmission of HIV can range from 15-45%. With the inclusion of antiretroviral drugs during pregnancy and the choice of delivery route this amounts to less than 2%. However ARV use during pregnancy has generated several questions regarding the adverse effects of the gestational and neonatal outcome. This study aims to analyze the risk factors for vertical transmission of HIV-1 seropositive pregnant women living in Rio Grande and the influence of the use of ARVs in pregnancy outcome. Among the 262 pregnant women studied the rate of vertical transmission of HIV was found to be 3.8%. Regarding the VT, there was a lower risk of transmission when antiretroviral drugs were used and prenatal care was conducted at the referral service. However, the use of ART did not influence the outcome of pregnancy. However, initiation of prenatal care after the first trimester had an influence on low birth weight, as well as performance of less than six visits increased the risk of prematurity. Therefore, the risk factors analyzed in this study appear to be related to the realization of inadequate pre-natal and maternal behavior.

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Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina

Revista Española de Quimioterapia ◽

10.37201/req/022.2021 ◽

2021 ◽

Author(s):

Diego Cecchini ◽

◽

Javier Sfalcin ◽

Inés Zapiola ◽

Alan Gómez ◽

...

Keyword(s):

Drug Resistance ◽

Pregnant Women ◽

Lower Risk ◽

Perinatal Transmission ◽

Viral Population ◽

Transmitted Drug Resistance ◽

Mutational Load ◽

Resistance Mutations ◽

Minority Variants ◽

Hiv 1

Objective. Argentina has reported high levels of transmitted drug resistance (TDR), in HIV-infected pregnant women by population sequencing. We aimed to describe, in patients with TDR, the percentage of quasispecies harboring resistance mutations (RAMs) and mutational load (ML). Patients and Methods. Retrospective study in a cohort of 40 naïve HIV-infected pregnant women, whose pretreatment samples had been genotyped by TRUGENE (period 2008-2014). Samples were re-sequenced with Ultra-deep Sequencing and ML was calculated considering baseline HIV-1 RNA load multiplied by the frequency of quasispecies harboring RAMs. Results. TDR for NNRTIs, NRTIs and PIs was 17.5% (n=7 patients), 10% (n=4), 12.5% (n=5) respectively. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). For NNRTIs, 78% of RAMs were present in >93.5% of viral population and ML was >1000 copies/mL (c/mL) for 89%, with a median (IQR) of 8330 c/ml (7738-29796). The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). For PIs, quasispecies with RAMs were <2.3% of viral population and ML was <350 c/mL for 77.8% of them. Conclusion. NNRTI-RAMs are predominant within the viral population, usually exceeding the threshold of 1000 c/mL, indicating potential higher risk of perinatal transmission. Conversely, PI mutations appear mostly as minority variants, with potential lower risk of transmission. Among NRTI, quasispecies harboring RAMs and ML values were variable.

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Reduction in the Risk of Vertical Transmission of HIV-1 Associated with Treatment of Pregnant Women with Orally Administered Zidovudine Alone

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology ◽

10.1097/00042560-199702010-00007 ◽

1997 ◽

Vol 14 (2) ◽

pp. 145-152 ◽

Cited By ~ 27

Author(s):

B. Joyce Simpson ◽

Eugene D. Shapiro ◽

Warren A. Andiman

Keyword(s):

Pregnant Women ◽

Vertical Transmission ◽

Vertical Transmission Of Hiv ◽

Hiv 1

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Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone

Genes ◽

10.3390/genes12091314 ◽

2021 ◽

Vol 12 (9) ◽

pp. 1314

Author(s):

George A. Yendewa ◽

Sulaiman Lakoh ◽

Sahr A. Yendewa ◽

Khadijah Bangura ◽

Andrés Tabernilla ◽

...

Keyword(s):

Drug Resistance ◽

Pregnant Women ◽

Sierra Leone ◽

Integrase Inhibitor ◽

Sub Saharan Africa ◽

Success Rates ◽

Resistance Mutations ◽

Cross Sectional ◽

Susceptibility Score ◽

Hiv 1

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2–9 years, 100% ART-experienced), 47 adolescents (age 10–18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.

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