scholarly journals Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Juanita Pang ◽  
Jennifer A Slyker ◽  
Sunando Roy ◽  
Josephine Bryant ◽  
Claire Atkinson ◽  
...  
Keyword(s):  
Breast Milk ◽  
Congenital Infection ◽  
Hiv Positive ◽  
Tissue Tropism ◽  
Cmv Infection ◽  
Women Studies ◽  
Infected Case ◽  
Hiv Positive Women ◽  
Hiv Positive Mothers

Cytomegalovirus (CMV) is the commonest cause of congenital infection (cCMVi) and particularly so among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers and identify the possibility of congenitally transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue-tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.

scholarly journals Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants.

2020 ◽  
Author(s):  
Juanita Pang ◽  
Jennifer A. Slyker ◽  
Sunando Roy ◽  
Josephine Bryant ◽  
Claire Atkinson ◽  
...  
Keyword(s):  
Breast Milk ◽  
Congenital Infection ◽  
Hiv Positive ◽  
Tissue Tropism ◽  
Cmv Infection ◽  
Women Studies ◽  
Infected Case ◽  
Hiv Positive Women ◽  
Hiv Positive Mothers

Cytomegalovirus (CMV) is the most congenital infection (cCMVi), and is particularly common among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly-developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers, and identify the possibility of congenitally-transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally-infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally-transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue-tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.

scholarly journals Breast Milk of HIV-Positive Mothers Has Potent and Species-SpecificIn VivoHIV-Inhibitory Activity

2015 ◽  
Vol 89 (21) ◽  
pp. 10868-10878 ◽  
Author(s):  
Angela Wahl ◽  
Caroline Baker ◽  
Rae Ann Spagnuolo ◽  
Lisa W. Stamper ◽  
Genevieve G. Fouda ◽  
...  
Keyword(s):  
Breast Milk ◽  
Hiv Infection ◽  
Inhibitory Activity ◽  
Hiv Transmission ◽  
Hiv Positive ◽  
Resource Limited Settings ◽  
Hiv Positive Women ◽  
Resource Limited ◽  
Hiv Positive Mothers

ABSTRACTDespite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed to anti-HIV factors in breast milk. Breast milk of HIV-negative women can inhibit HIV infection. However, the HIV-inhibitory activity of breast milk from HIV-positive mothers has not been evaluated. In addition, while significant differences in breast milk composition between transmitting and nontransmitting HIV-positive mothers have been correlated with transmission risk, the HIV-inhibitory activity of their breast milk has not been compared. This knowledge may significantly impact the design of prevention approaches in resource-limited settings that do not deny infants of HIV-positive women the health benefits of breast milk. Here, we utilized bone marrow/liver/thymus humanized mice to evaluate thein vivoHIV-inhibitory activity of breast milk obtained from HIV-positive transmitting and nontransmitting mothers. We also assessed the species specificity and biochemical characteristics of milk'sin vivoHIV-inhibitory activity and its ability to inhibit other modes of HIV infection. Our results demonstrate that breast milk of HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast milk can prevent multiple routes of infection. Most importantly, this activity is unique to human milk. Our results also suggest multiple factors in breast milk may contribute to its HIV-inhibitory activity. Collectively, our results support current recommendations that HIV-positive mothers in resource-limited settings exclusively breastfeed in combination with antiretroviral therapy.IMPORTANCEApproximately 240,000 children become infected with HIV annually, the majority via breastfeeding. Despite daily exposure to virus in breast milk, most infants breastfed by HIV-positive women do not acquire HIV. The low risk of breastfeeding-associated HIV transmission is likely due to antiviral factors in breast milk. It is well documented that breast milk of HIV-negative women can inhibit HIV infection. Here, we demonstrate, for the first time, that breast milk of HIV-positive mothers (nontransmitters and transmitters) inhibits HIV transmission. We also demonstrate that breast milk can prevent multiple routes of HIV acquisition and that this activity is unique to human milk. Collectively, our results support current guidelines which recommend that HIV-positive women in resource-limited settings exclusively breastfeed in combination with infant or maternal antiretroviral therapy.

scholarly journals Describing Point of Entry into Care and Being Lost to Program in a Cohort of HIV Positive Pregnant Women in a Large Urban Centre in Uganda

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Rachel Musomba ◽  
Frank Mubiru ◽  
Shadia Nakalema ◽  
Hope Mackline ◽  
Ivan Kalule ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Older Women ◽  
First Trimester ◽  
Hiv Positive ◽  
Urban Centre ◽  
Factors Associated ◽  
Point Of Entry ◽  
Art Initiation ◽  
Hiv Positive Women

Introduction. We aim to describe the time of entry into care and factors associated with being lost to program (LTP) in pregnant women on Option B Plus in an integrated HIV and antenatal care (ANC) clinic in Uganda. Methods. We included all pregnant women enrolled into the integrated HIV-ANC clinic from January 2012 to 31st July 2014, while the follow up period extended up to October 30th 2015. LTP was defined as being out of care for ≥3 months. Results. Overall 856 women were included. Only 36.4% (86/236) of the women were enrolled in the first trimester. Overall 69 (8.1%) were LTP. In the multivariate analysis older women (HR: 0.80 per five-year increase, CI: 0.64–1.0, and P=0.060) and women on ART at the time of pregnancy (0.58, CI: 0.34–0.98, and P=0.040) were more likely not to be LTP. Among women already on ART at the time of pregnancy no factor was associated with LTP. Conclusion. Our results suggest the need for interventions to enhance prompt linkage of HIV positive women to HIV services for ART initiation and for increased retention particularly in young and ART naive women.

scholarly journals Recurrent maternal CMV infection associated with symptomatic congenital infection: results from a questionnaire study in Portugal

2019 ◽  
Vol 3 (1) ◽  
pp. e000455
Author(s):  
Paulo Paixão ◽  
Maria João Brito ◽  
Daniel Virella ◽  
Maria Teresa Neto
Keyword(s):  
Primary Infection ◽  
Recurrent Infection ◽  
Congenital Infection ◽  
High Avidity ◽  
Maternal Infection ◽  
Cmv Infection ◽  
Congenital Cmv Infection ◽  
Missed Diagnosis ◽  
Congenital Cmv

ObjectiveHuman cytomegalovirus (CMV) is the most widespread agent of congenital infection in humans and is still a challenging issue. Despite lower rates of vertical transmission being associated with recurrent infection when compared with primary infection, the first still represents the majority of congenital infections worldwide. Based on data from active reporting, we explored the influence of maternal primary/non-primary infection both on the presentation and outcome of congenital CMV infection in early childhood.DesignInfants with positive viruria during the first 3 weeks of life were reported through the Portuguese Paediatric Surveillance Unit.PatientsInfants born between 2006 and 2011 with confirmed congenital CMV infection.MethodsMaternal infection was considered primary if CMV IgG seroconversion occurred during pregnancy or low avidity IgG was documented; it was considered non-primary if positive IgG was documented before pregnancy or high avidity CMV IgG was present early in pregnancy. Follow-up questionnaires were sent up to 6 years of age.ResultsForty confirmed cases of congenital CMV infection were reported (6.6:105 live births, 95% CI 4.81 to 8.92); 22 out of 40 were asymptomatic. The odds for non-primary maternal infection if the offspring was symptomatic at birth were 6.2 (95% CI 1.2 to 32.27).ConclusionThe reported number of confirmed cases of congenital CMV infection was much lower than expected. Under-reporting and missed diagnosis were considered possible reasons. Non-primary maternal infections were associated with symptomatic congenital CMV infection in the offspring. Maternal recurrent infections can have a significant impact on the total number of symptomatic infections in Portugal.

Successful Community Follow-up and Reduced Recidivism in HIV Positive Women Prisoners

1997 ◽  
Vol 4 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Joo Y. Kim ◽  
Josiah Rich ◽  
Sally Zierler ◽  
Kevin Lourie ◽  
Kevin Vigilante ◽  
...  
Keyword(s):  
Women Prisoners ◽  
Hiv Positive ◽  
Hiv Positive Women

scholarly journals Challenges in Assessing Outcomes among Infants of Pregnant HIV-Positive Women Receiving ART in Uganda

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Barbara Castelnuovo ◽  
Frank Mubiru ◽  
Ivan Kalule ◽  
Shadia Nakalema ◽  
Agnes Kiragga
Keyword(s):  
Clinical Trials ◽  
Pregnant Women ◽  
Median Time ◽  
Hiv Transmission ◽  
Cd4 Count ◽  
Hiv Positive ◽  
Hiv Positive Women

Since 2012, the WHO recommends lifelong ART with TDF+FTC/3TC+EFV for all HIV-positive pregnant and breastfeeding women (Option B-plus). In this analysis we describe the proportion of early and late transmission in mothers with high retention in Kampala, Uganda. We included 700 pregnant women from January 2012 to August 2014 with a follow-up extended to August 2016; the median age was 31 years (IQR: 26–35), 36.3% in WHO stage 3/4; median CD4 count was 447 cells/μL (IQR: 301–651) and 73.3% were already on ART for a median time of 28 (IQR: 10–57) months; 52% infants were male and median weight was 3.2 Kg (IQR: 2.5–3.5). Five hundred and sixty-five (80.7%) infants had at least one test for HIV; 22 (3.1%) infants died, all with unknown serostatus; 3 tested positive at week 6 and one additional at months 12 and 18. Two of the mothers of the 4 HIV-positive infants were ART-naïve at the time of pregnancy. We report very low documented HIV transmission comparable with those reported in clinical trials settings; however, demonstrating the efficacy of Option B-plus in terms of averted transmission in routine settings is challenging since high proportion of infants do not have documented HIV tests.

scholarly journals A prospective study of demographic features and quality of life in HIV-positive women with cervical cancer treated at Tygerberg Hospital

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
George Du Toit ◽  
Martin Kidd
Keyword(s):  
Quality Of Life ◽  
Cervical Cancer ◽  
Cancer Treatment ◽  
Hiv Positive ◽  
Hiv Positive Women ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Hiv Negative

Background: Cervical cancer and human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS) both have a high incidence in South Africa. Cervical cancer treatment of HIV-positive women poses challenges. Treatment-related changes in quality of life (QOL) of such women are important to future treatment protocols.Aim: To examine demographic data of HIV-negative and HIV-positive women at diagnosis of cervical cancer and describe their changes in QOL as a result of treatment.Methods and materials: All newly diagnosed patients with cervical cancer at Tygerberg Hospital were approached to participate in the study. The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the Cervix Cancer Module (QLQ-CX24) were used. General QOL was measured with the EORTC QLQ-C30 and cervical-specific QOL with the QLQ-CX24 questionnaire. The patients completed the questionnaire at diagnosis, on completion of treatment and at 3 months’ follow-up.Results: The study included a total of 221 women of whom 22% were HIV-positive; the latter were younger and of higher educational level than the rest. Mean monthly income and stage distribution was similar between the two groups. HIV-positive patients underwent radiation therapy more commonly than chemoradiation. HIV-positive women showed statistically significantly higher loss to follow-up during the study. HIV-positive women experienced no improvement in insomnia, appetite loss, nausea, vomiting, diarrhoea, social role or any of the sexual domains. In contrast, HIV-negative women experienced statistically significant improvement in all sexual domains other than sexual/vaginal functioning. The QOL improvement of HIV-negative women was statistically significantly greater than their HIV-positive counterparts in the majority of QOL domains. Global health improved in both groups, with HIV-negative women experiencing greater improvement. HIV-positive women experienced an initial decline of peripheral neuropathy (PN) symptoms post treatment with a return to pretreatment values at 3 months’ follow-up. The change in PN was statistically significant between the HIV-negative and HIV-positive women.Conclusion: Demographic differences exist between the HIV-negative and HIV-positive groups. The differential outcome in the QOL of HIV-positive and HIV-negative women treated for cervical cancer might be related to persistence of AIDS-related symptoms on completion of cervical cancer treatment.

scholarly journals Observational study of cytomegalovirus from breast milk and necrotising enterocolitis

2019 ◽  
Vol 105 (3) ◽  
pp. 259-265 ◽  
Author(s):  
Ravi Mangal Patel ◽  
Neeta Shenvi ◽  
Andrea Knezevic ◽  
Michael Hinkes ◽  
George W Bugg ◽  
...  
Keyword(s):  
Viral Load ◽  
Birth Weight ◽  
Breast Milk ◽  
Very Low Birth Weight ◽  
Congenital Infection ◽  
Necrotising Enterocolitis ◽  
Cmv Infection ◽  
Low Birth Weight Infants ◽  
Cox Models ◽  
The Relationship

ObjectiveTo evaluate the relationship between cytomegalovirus (CMV) exposure from breast milk and risk of necrotising enterocolitis (NEC).DesignSecondary analysis of a multicentre, observational cohort study. Maternal breast milk and infant serum or urine were serially evaluated by nucleic acid testing at scheduled intervals for CMV. Infants with evidence of congenital infection were excluded. Competing-risks Cox models, with adjustment for confounders, were used to evaluate the relationship between breast milk CMV exposure or postnatal CMV infection and NEC.SettingThree neonatal intensive care units in Atlanta, Georgia.PatientsInfants with a birth weight≤1500 grams.ExposuresMaximal CMV viral load in breast milk in the first 14 days after birth or postnatal CMV infection. Two different approaches were used to assess the timing of onset of CMV infection (midpoint or early).Main outcome measuresNEC, defined as Bell stage II or greater.ResultsAmong 596 enrolled infants, 457 (77%) were born to CMV seropositive mothers and 33 developed postnatal CMV infection (cumulative incidence 7.3%, 95% CI 5.0% to 10.1%). The incidence of NEC was 18% (6/33) among infants with CMV infection, compared with 7% (37/563) among infants without infection (adjusted cause-specific HR (CSHR): 2.81; 95% CI 0.73 to 10.9 (midpoint); 6.02; 95% CI 1.28 to 28.4 (early)). Exposure to higher breast milk CMV viral load was associated with a higher risk of NEC (adjusted CSHR per twofold increase 1.28; 95% CI 1.06 to 1.54).ConclusionsCMV exposure from breast milk may be associated with the development of NEC in very low birth weight infants.

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