Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 41 Records) |
Query Trace: King CC[original query] |
---|
Protozoan-viral-bacterial co-infections alter galectin levels and associated immunity mediators in the female genital tract
Fichorova RN , DeLong AK , Cu-Uvin S , King CC , Jamieson DJ , Klein RS , Sobel JD , Vlahov D , Yamamoto HS , Mayer KH . Front Cell Infect Microbiol 2021 11 649940 Co-infections with sexually transmittable pathogens are common and more likely in women with disturbed vaginal bacteriome. Among those pathogens, the protozoan parasite Trichomonas vaginalis (TV) is most common after accounting for the highly persistent DNA viruses human papillomavirus (HPV) and genital herpes. The parasitic infection often concurs with the dysbiotic syndrome diagnosed as bacterial vaginosis (BV) and both are associated with risks of superimposed viral infections. Yet, the mechanisms of microbial synergisms in evading host immunity remain elusive. We present clinical and experimental evidence for a new role of galectins, glycan-sensing family of proteins, in mixed infections. We assessed participants of the HIV Epidemiology Research Study (HERS) at each of their incident TV visits (223 case visits) matched to controls who remained TV-negative throughout the study. Matching criteria included age, race, BV (by Nugent score), HIV status, hysterectomy, and contraceptive use. Non-matched variables included BV status at 6 months before the matched visit, and variables examined at baseline, within 6 months of and/or at the matched visit e.g. HSV-2, HPV, and relevant laboratory and socio-demographic parameters. Conditional logistic regression models using generalized estimating equations calculated odds ratios (OR) for incident TV occurrence with each log(10) unit higher cervicovaginal concentration of galectins and cytokines. Incident TV was associated with higher levels of galectin-1, galectin-9, IL-1β and chemokines (ORs 1.53 to 2.91, p <0.001). Galectin-9, IL-1β and chemokines were up and galectin-3 down in TV cases with BV or intermediate Nugent versus normal Nugent scores (p <0.001). Galectin-9, IL-1β and chemokines were up in TV-HIV and down in TV-HPV co-infections. In-vitro, TV synergized with its endosymbiont Trichomonasvirus (TVV) and BV bacteria to upregulate galectin-1, galectin-9, and inflammatory cytokines. The BV-bacterium Prevotella bivia alone and together with TV downregulated galectin-3 and synergistically upregulated galectin-1, galectin-9 and IL-1β, mirroring the clinical findings of mixed TV-BV infections. P. bivia also downregulated TVV+TV-induced anti-viral response e.g. IP-10 and RANTES, providing a mechanism for conducing viral persistence in TV-BV co-infections. Collectively, the experimental and clinical data suggest that galectin-mediated immunity may be dysregulated and exploited by viral-protozoan-bacterial synergisms exacerbating inflammatory complications from dysbiosis and sexually transmitted infections. |
Diversity of the hepatitis C virus NS5B gene during HIV co-infection.
Ngwaga T , Kong L , Lin D , Schoborg C , Taylor LE , Mayer KH , Klein RS , Celentano DD , Sobel JD , Jamieson DJ , King CC , Tavis JE , Blackard JT . PLoS One 2020 15 (8) e0237162 Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve women with HIV/HCV co-infection and CD4 cell count ≥350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 ≥350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation. |
Inter- and intra-host sequence diversity reveal the emergence of viral variants during an overwintering epidemic caused by dengue virus serotype 2 in southern Taiwan
Ko HY , Li YT , Chao DY , Chang YC , Li ZT , Wang M , Kao CL , Wen TH , Shu PY , Chang GJ , King CC . PLoS Negl Trop Dis 2018 12 (10) e0006827 Purifying selection during dengue viral infection has been suggested as the driving force of viral evolution and the higher complexity of the intra-host quasi-species is thought to offer an adaptive advantage for arboviruses as they cycle between arthropod and vertebrate hosts. However, very few studies have been performed to investigate the viral genetic changes within (intra-host) and between (inter-host) humans in a spatio-temporal scale. Viruses of different serotypes from various countries imported to Taiwan cause annual outbreaks. During 2001-2003, two consecutive outbreaks were caused by dengue virus serotype 2 (DENV-2) and resulted in a larger-scale epidemic with more severe dengue cases in the following year. Phylogenetic analyses showed that the viruses from both events were similar and related to the 2001 DENV-2 isolate from the Philippines. We comprehensively analyzed viral sequences from representative dengue patients and identified three consensus genetic variants, group Ia, Ib and II, with different spatio-temporal population dynamics. The phylodynamic analysis suggested group Ib variants, characterized by lower genetic diversity, transmission rate, and intra-host variant numbers, might play the role of maintenance variants. The residential locations among the patients infected by group Ib variants were in the outer rim of case clusters throughout the 2001-2003 period whereas group Ia and II variants were located in the centers of case clusters, suggesting that group Ib viruses might serve as "sheltered overwintering" variants in an undefined ecological niche. Further deep sequencing of the viral envelope (E) gene directly from individual patient serum samples confirmed the emergence of variants belonging to three quasi-species (group Ia, Ib, and II) and the ancestral role of the viral variants in the latter phase of the 2001 outbreak contributed to the later, larger-scale epidemic beginning in 2002. These findings enhanced our understanding of increasing epidemic severity over time in the same epidemic area. It also highlights the importance of combining phylodynamic and deep sequencing analysis as surveillance tools for detecting dynamic changes in viral variants, particularly searching for and monitoring any specific viral subpopulation. Such subpopulations might have selection advantages in both fitness and transmissibility leading to increased epidemic severity. |
Availability and use of contraceptive implants in Jamaica: Results of a review of medical records and a survey of reproductive healthcare providers in six public health centres
Chevalier MS , King CC , Jarrett S , Sutherland S , Hill SM , Kourtis AP . West Indian Med J 2018 67 (2) 114-121 Objective: The prevalence of sub-dermal contraceptive implant use in Jamaica is low, despite growing international acceptance of long-acting reversible contraception. This study assessed the availability, effectiveness, side-effects and utilization of sub-dermal contraceptive implants and described the characteristics of users over a one-year period. Methods: We reviewed the medical records of women aged 15-45 years who utilized contraceptive implant-related services at any of the six included public health centres in Jamaica during 2013, and surveyed 20 available reproductive healthcare providers. Results: In 2013, 738 women attended a Jamaican public health centre for contraceptive implant services: 493 (66.8%) for insertion, 202 (27.4%) for removal and 53 (7.2%) for follow- up visits (10 women had the same implant inserted and removed in 2013). The women's median age was 26.0 years, 24.3% were <= 18 years, and 85.9% had >= 1 child. Most women (68.5%) did not have documented side-effects; irregular bleeding, the most commonly documented side-effect, was recorded for 24%. Of the 493 women who had implants inserted, three (0.6%) were identified to be pregnant within three months of insertion. Among the 202 women who had implants removed, 11 (5.4%) experienced complications with removal. Reproductive healthcare providers highlighted the need for an expansion of contraceptive implant availability and provider training. Conclusion: Sub-dermal implants have few insertion complications and side-effects and are effective, but were underutilized in Jamaica. Increased implant availability and enhanced reproductive healthcare provider training may improve implant utilization and reduce unintended pregnancy rates in Jamaica. |
Examining the contraceptive decisions of young, HIV-infected women: a qualitative study
Brown JL , Haddad LB , Gause NK , Cordes S , Bess C , King CC , Hatfield-Timajchy K , Chakraborty R , Kourtis A . Women Health 2018 59 (3) 305-317 This study qualitatively examined factors that influenced contraceptive choices in a sample of young, HIV-infected women. Individual qualitative interviews were conducted among 30 vertically- and horizontally-HIV-infected women (n = 26 African American) from the ages of 14 to 24 years (Mean age = 20.9 years). We recruited sample groups with the following characteristics: (a) current contraceptive/condom use with >/=1 child (n = 11); (b) current contraceptive/condom use with no children (n = 12); and (c) no current contraceptive/condom use with no children (n = 7). A semi-structured interview guide was used to ask participants about factors influencing past and current contraceptive choices. Individual interviews were digitally recorded and transcribed verbatim; analyses to identify core themes were informed by the Grounded Theoretical approach. Young, HIV-infected women did not identify their HIV serostatus or disease-related concerns as influential in their contraceptive decisions. However, they reported that recommendations from healthcare providers and input from family and friends influenced their contraceptive choices. They also considered a particular method's advantages (e.g., menstrual cycle improvements) and disadvantages (e.g., increased pill burden) when selecting a method. Findings suggested that HIV-infected young women's contraceptive decisions were influenced by factors other than those related to their infection. |
Prevalence, magnitude, and correlates of HIV-1 genital shedding in women on antiretroviral therapy
King CC , Ellington SR , Davis NL , Coombs RW , Pyra M , Hong T , Mugo N , Patel RC , Lingappa JR , Baeten JM , Kourtis AP . J Infect Dis 2017 216 (12) 1534-1540 Background: Genital human immunodeficiency virus (HIV) RNA shedding can continue despite HIV being undetectable in blood, and can be associated with transmission. Methods: We included African women on antiretroviral therapy (ART). Linear and generalized linear mixed models were used to compare the magnitude and prevalence of genital shedding, respectively, by time since ART initiation. Multivariable logistic regression with generalized estimating equations was used to assess predictors of genital shedding among women with undetectable plasma viral load (VL). Results: Among 1114 women, 5.8% of visits with undetectable plasma VL and 23.6% of visits with detectable VL had genital shedding. The proportion of visits with genital shedding decreased with time since ART initiation but the magnitude of shedding remained unchanged when plasma VL was undetectable (P = .032). Prevalence of shedding did not vary by time since ART initiation when plasma VL was detectable (P = .195), though the magnitude of shedding significantly increased (P = .04). Predictors of genital shedding were HIV disease stage, antiretroviral regimen, and genital ulcers or cervical tenderness. Discussion: In addition to ART, reducing immune activation through prevention and treatment of HIV-related conditions and genital tract infections may decrease the risk of HIV-1 shedding and potential transmission. |
Effects of concurrent exposure to antiretrovirals and cotrimoxazole prophylaxis among HIV-exposed, uninfected infants
Ewing AC , King CC , Wiener JB , Chasela CS , Hudgens MG , Kamwendo D , Tegha G , Hosseinipour MC , Jamieson DJ , Van der Horst C , Kourtis AP . AIDS 2017 31 (18) 2455-2463 BACKGROUND: Given the potential of cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV-exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with antiretroviral agents that have overlapping toxicity profiles. METHODS: We used data from the Breastfeeding, Antiretrovirals, and Nutrition study (2004-2010) to evaluate the association of CPT and antiretrovirals with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2006 HEU infants in Lilongwe, Malawi. Hazards of severe outcomes (anemia, neutropenia, and elevated alanine aminotransferase), as defined by the National Institutes of Health, were compared using Cox regression models, according to time-varying CPT (implemented June 2006), antiretroviral treatment arm (maternal triple antiretroviral, infant nevirapine, or none during 6 months of breastfeeding), and their interaction. The effects of these treatments on hemoglobin, neutrophil, and alanine aminotransferase levels were assessed using linear mixed models. RESULTS: In Cox models, CPT was associated with an increase in severe neutropenia [hazard ratio 1.97 (1.01, 3.86)] and a decrease in severe anemia (hazard ratio 0.65 (0.48, 0.88)]. Interactions between CPT and antiretroviral treatment were not significant. By 36 weeks, there was a significant association of CPT with increased hemoglobin levels regardless of antiretroviral drug exposure. CONCLUSIONS: In addition to expected associations with increased hazard of severe neutropenia and decreased neutrophil count, CPT was associated with reduced hazard of severe anemia and higher infant blood hemoglobin. This provides further support for CPT use in HEU infants in malaria-endemic resource-limited settings where anemia is prevalent. |
Cytokine/chemokine expression associated with Human Pegivirus (HPgV) infection in women with HIV
Blackard JT , Ma G , Welge JA , Taylor LE , Mayer KH , Klein RS , Celentano DD , Sobel JD , Jamieson DJ , King CC . J Med Virol 2017 89 (11) 1904-1911 A beneficial impact of the Human Pegivirus (HPgV) - formerly called GB virus C (GBV-C) - on HIV disease progression has been reported previously. One possible mechanism by which HPgV inhibits HIV replication is an alteration of the cytokine/chemokine milieu. Their expression has not been specifically evaluated in women despite their influence on disease progression and the possibility of gender-based differences in expression. Moreover, the impact of HPgV genotype on cytokine/chemokine expression is unknown. Sera levels of IL-2, IL-4, IL-7, IL-8, IL-10, IL-12p70, IL-13, IFNgamma, TNFalpha, IP-10, MIP-1alpha, MIP-1beta, and TGF-beta1 were quantified in 150 HIV-positive women based on HPgV RNA status. Cytokines/chemokines with detection rates of at least 50% included IL-2, IL-4, IL-8, IL-10, IL-12p70, IFNgamma, TNFalpha, IP-10, MIP-1alpha, MIP-1beta, and TGF-beta1 . Absolute values were significantly higher for HPgV positive compared to HPgV negative women for IL-7, IL-13, IL-12p70, and IFNgamma. Absolute values were significantly lower for HPgV positive women for IL-4, IL-8, TGF-beta1 , and IP-10. IFNgamma values were higher for HPgV genotype 2 than for genotype 1 (p = 0.036). Further study of cytokine/chemokine regulation by HPgV may ultimately lead to the development of novel therapeutic agents to treat HIV infection and/or the design of vaccine strategies that mimic the 'protective' effects of HPgV replication. |
Cytomegalovirus infection in pregnancy
Davis NL , King CC , Kourtis AP . Birth Defects Res 2017 109 (5) 336-346 Cytomegalovirus (CMV) is a DNA herpesvirus that is common worldwide. The two known main sources of primary CMV infection during pregnancy are through sexual activity and contact with young children. Primary infection occurs in approximately 1 to 4% of pregnancies, and is mostly asymptomatic in immunocompetent adults. However, primary infection may manifest as a mild mononucleosis or flu-like syndrome with persistent fever and fatigue. CMV can be transmitted from mother-to-child in utero, intrapartum, or during breastfeeding. Intrauterine transmission can lead to congenital CMV infection, a leading cause of permanent hearing and vision loss and neurological disability among children. Congenital CMV transmission rates are as high as 50% in women who acquire primary CMV infection during pregnancy, and less than 2% in women with nonprimary infection. There is no licensed CMV vaccine. Good hygiene practices and avoiding intimate contact with young children (e.g., kissing on the mouth and sharing utensils) have been suggested as an approach to prevent maternal primary CMV infection during pregnancy, but remains an unproven method of reducing the risk of congenital CMV infection. Approximately 1 in 10 infants who acquire CMV in utero will have clinical signs at birth, and an additional 10 to 15% will go on to develop late-onset sequelae. Antiviral treatment prenatally and postnatally has not proven effective at preventing congenital or postnatal CMV infection, and is not recommended for routine clinical care. However, antiviral treatment when initiated in the first month of life for symptomatic congenital CMV infection is recommended for improved neurodevelopmental and audiologic outcomes. Birth Defects Research 109:336-346, 2017. c. |
Maternal and neonatal outcomes among women with HIV infection and their infants in Malawi
Chevalier MS , King CC , Ellington S , Wiener J , Kayira D , Chasela CS , Jamieson DJ , Kourtis AP . Int J Gynaecol Obstet 2017 137 (3) 282-289 OBJECTIVE: To describe maternal and neonatal morbidity and mortality among women with HIV infection and their infants. METHODS: A secondary analysis was undertaken of data obtained in the BAN Study, a trial of postnatal antiretrovirals among pregnant women with HIV infection enrolled in 2004-2010. Mothers and infants had 13 scheduled visits through 48 weeks of follow-up. Serious maternal morbidity and mortality were examined at delivery (n=2791), from delivery to 6 weeks later (n=2369) and from 7 to 48 weeks (n=1980). Neonatal morbidity and mortality were examined (n=2685). RESULTS: Of 2791 deliveries, 169 (6.1%) were by cesarean (153 emergency). Compared with women with vaginal delivery, those with cesarean delivery had lower prenatal HIV viral loads (P=0.016) and increased odds of pre-eclampsia/eclampsia (odds ratio [OR] 10.8, 95% CI 4.4-26.8). Women with cesarean delivery also had increased odds of serious infection with 14 days of delivery (OR 3.0, 95% CI 1.3-7.4) and severe anemia (grade 3 or 4) by 6 weeks (OR 6.7, 95% CI 2.3-19.1). Infants born by cesarean had increased odds of a low 5-minute Apgar score (OR 8.1, 95% CI 3.5-18.6) and admission to an intensive care unit (OR 5.4, 95% CI 3.7-7.8). CONCLUSION: Odds of serious maternal and neonatal morbidity were higher after cesarean than vaginal delivery, despite lower maternal viral loads. This article is protected by copyright. All rights reserved. |
Effect of postnatal HIV treatment on clinical mastitis and breast inflammation in HIV-infected breast-feeding women
Zadrozny S , Westreich D , Hudgens MG , Chasela C , Jamieson DJ , Martinson F , Zimba C , Tegha G , Hoffman I , Miller WC , Pence BW , King CC , Kourtis AP , Msungama W , van der Horst C . Paediatr Perinat Epidemiol 2017 31 (2) 134-143 BACKGROUND: The relationship between mastitis and antiretroviral therapy among HIV-positive, breast-feeding women is unclear. METHODS: In the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, conducted in Lilongwe, Malawi, 2369 mother-infant pairs were randomized to a nutritional supplement group and to one of three treatment groups: maternal antiretroviral therapy (ART), infant nevirapine (NVP) or standard of care for 24 weeks of exclusive breast-feeding and 4 weeks of weaning. Among 1472 HIV-infected women who delivered live infants between 2004 and 2007, we estimated cumulative incidence functions and sub-distribution hazard ratios (HR) of mastitis or breast inflammation comparing women in maternal ART (n = 487) or infant nevirapine (n = 492) groups to the standard of care (n = 493). Nutritional supplement groups (743 took, 729 did not) were also compared. RESULTS: Through 28-weeks post-partum, 102 of 1472 women experienced at least one occurrence of mastitis or breast inflammation. The 28-week risk was higher for maternal ART (risk difference (RD) 4.5, 95% confidence interval (CI) 0.9, 8.1) and infant NVP (RD 3.6, 95% CI 0.3, 6.9) compared to standard of care. The hazard of late-appearing mastitis or breast inflammation (from week 5-28) was also higher for maternal ART (HR 6.7, 95% CI 2.0, 22.6) and infant NVP (HR 5.1, 95% CI 1.5, 17. 5) compared to the standard of care. CONCLUSIONS: Mastitis or breast inflammation while breast-feeding is a possible side effect for women taking prophylactic ART and women whose infants take NVP, warranting additional research in the context of postnatal HIV transmission. |
A randomized clinical trial on the effects of progestin contraception in the genital tract of HIV-infected and uninfected women in Lilongwe, Malawi: Addressing evolving research priorities
Kourtis AP , Haddad L , Tang J , Chinula L , Hurst S , Wiener J , Ellington S , Nelson JA , Corbett A , De Paris K , King CC , Hosseinipour M , Hoffman IF , Jamieson DJ . Contemp Clin Trials 2016 52 27-34 Hormonal contraception is central in the prevention of unintended pregnancy; however there are concerns that certain methods may increase the risk of HIV acquisition and transmission. Hormonal contraceptives may modify the genital mucosa in several ways, however the mechanisms are incompletely understood. Few studies have examined genital HIV shedding prospectively before and after initiation of hormonal contraception. The effects of hormonal contraception on genital HIV shedding in the setting of antiretroviral therapy (ART) are also unknown. We designed a pilot clinical trial in which HIV-infected and uninfected women were randomized to either depot medroxyprogesterone acetate (DMPA) injectable or levonorgestrel (LNG) implant in Lilongwe, Malawi. The objectives were to: 1) assess the effect and compare the impact of type of progestin contraception (injectable versus implant) on HIV genital shedding among HIV-infected women, 2) assess the effect and compare the impact of type of progestin contraception on inflammatory/immune markers in the genital tract of both HIV-infected and uninfected women, and 3) assess the interaction of progestin contraception and ART by examining contraceptive efficacy and ART efficacy. An additional study aim was to determine the feasibility and need for a larger study of determinants of HIV transmissibility and acquisition. As injectable contraception is widely used in many parts of the world with high HIV prevalence, this study will provide important information in determining the need for and feasibility of a larger study to address these questions that can impact the lives of millions of women living with or at risk for HIV. |
Effect of pregnancy on response to antiretroviral therapy in HIV-infected African women
Kourtis AP , Wiener J , King CC , Heffron R , Mugo NR , Nanda K , Pyra M , Donnell D , Celum C , Lingappa JR , Baeten JM . J Acquir Immune Defic Syndr 2016 74 (1) 38-43 BACKGROUND: While most recent evidence does not support a role for pregnancy in accelerating HIV disease progression, very little information is available on the effects of incident pregnancy on response to antiretroviral therapy (ART). Hormonal, immune and behavioral changes during pregnancy may influence response to ART. We sought to explore the effects of incident pregnancy (after ART initiation) on virologic, immunologic, and clinical response to ART. METHODS: Data were collected from HIV-infected women participating in 3 prospective studies (Partners in Prevention HSV/HIV Transmission Study, Couples Observational Study, and Partners PrEP Study) from seven countries in Africa from 2004 to 2012. Women were included in this analysis if they were ≤ 45 years of age, were started on ART during the study and were not pregnant at ART initiation. Pregnancy was treated as a time-dependent exposure variable covering the duration of pregnancy, including all pregnancies occurring after ART initiation. Virologic failure was defined as a viral load (VL) greater than 400 copies/ml ≥6 months after ART initiation and viral suppression was defined as viral load ≤400 copies/ml. Multivariable Cox proportional hazards models were used to assess the association between pregnancy and time to viral suppression, virologic failure, WHO clinical stage III/IV and death. Linear mixed effects models were used to assess the association between pregnancy and CD4+ count and VL. All analyses were adjusted for confounders, including pre-ART CD4+ count and plasma VL. RESULTS: A total of 1041 women were followed, contributing 1196.1 person-years of follow-up. Median CD4+ count prior to ART initiation was 276 cells/mm (IQR, 209-375); median pre-ART VL was 17,511 copies/ml (IQR, 2,480-69,286). One-hundred ten women became pregnant after ART initiation. Pregnancy was not associated with time to viral suppression (adjusted HR, 1.20, 95% CI, 0.82-1.77), time to virologic failure (adjusted HR, 0.67, 95% CI, 0.37-1.22), time to WHO clinical stage III or IV (adjusted HR, 0.79, 95% CI, 0.19-3.30) or time to death (adjusted HR, 2.04, 95% CI, 0.25-16.8). Incident pregnancy was associated with an adjusted mean decrease in CD4+ T cell count of 47.3 cells/mm (p<0.001), but not with difference in VL (p=0.06). CONCLUSIONS: For HIV-infected women on ART, incident pregnancy does not affect virologic control or clinical HIV disease progression. A modest decrease in CD4+ T cell count could be due to physiologic effects of pregnancy. |
Improving dengue viral antigens detection in dengue patient serum specimens using a low pH glycine buffer treatment
Shen WF , Galula JU , Chang GJ , Wu HC , King CC , Chao DY . J Microbiol Immunol Infect 2015 50 (2) 167-174 BACKGROUND/PURPOSES: Early diagnosis of dengue virus (DENV) infection to monitor the potential progression to hemorrhagic fever can influence the timely management of dengue-associated severe illness. Nonstructural protein 1 (NS1) antigen detection in acute serum specimens has been widely accepted as an early diagnostic assay for dengue infection; however, lower sensitivity of the NS1 antigen-capture enzyme-linked immunosorbent assay (Ag-ELISA) in secondary dengue viral infection has been reported. METHODS: In this study, we developed two forms of Ag-ELISA capable of detecting E-Ag containing virion and virus-like particles, and secreted NS1 (sNS1) antigens, respectively. The temporal kinetics of viral RNA, sNS1, and E-Ag were evaluated based on the in vitro infection experiment. Meanwhile, a panel of 62 DENV-2 infected patients' sera was tested. RESULTS: The sensitivity was 3.042 ng/mL and 3.840 ng/mL for sNS1 and E, respectively. The temporal kinetics of the appearance of viral RNA, E, NS1, and infectious virus in virus-infected tissue culture media suggested that viral RNAs and NS1 antigens could be detected earlier than E-Ag and infectious virus. Furthermore, a panel of 62 sera from patients infected by DENV Serotype 2 was tested. Treating clinical specimens with the dissociation buffer increased the detectable level of E from 13% to 92% and NS1 antigens from 40% to 85%. CONCLUSION: Inclusion of a low-pH glycine buffer treatment step in the commercially available Ag-ELISA is crucial for clinical diagnosis and E-containing viral particles could be a valuable target for acute DENV diagnosis, similar to NS1 detection. |
Association of HIV-1 envelope-specific breast milk IgA responses with reduced risk of postnatal mother-to-child transmission of HIV-1
Pollara J , McGuire E , Fouda GG , Rountree W , Eudailey J , Overman RG , Seaton KE , Deal A , Edwards RW , Tegha G , Kamwendo D , Kumwenda J , Nelson JA , Liao HX , Brinkley C , Denny TN , Ochsenbauer C , Ellington S , King CC , Jamieson DJ , van der Horst C , Kourtis AP , Tomaras GD , Ferrari G , Permar SR . J Virol 2015 89 (19) 9952-61 Infants born to HIV-1 infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk, and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1 infected mothers are repeatedly exposed to virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1 transmitting and nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitude of the breast milk IgA and secretory IgA response against HIV-1 envelope proteins was associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding, and development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation. |
Time of HIV diagnosis in infants after weaning from breast milk
Kourtis AP , King CC , Nelson J , Jamieson DJ , van der Horst C . AIDS 2015 29 (14) 1897-8 Of 28 infants diagnosed with HIV infections after breastfeeding cessation in a large clinical trial (the Breastfeeding, Antiretrovirals and Nutrition Study), 19 (68%) were first detected more than 6 weeks (and up to 168 days) post reported weaning. The current recommendation for HIV testing of infants is at 6 weeks after weaning; these data argue for repeat HIV testing of infants up to 6 months after breastfeeding cessation, so that no infant HIV infections are missed. |
Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding
King CC , Kourtis AP , Persaud D , Nelson JA , Ziemniak C , Hudgens MG , Tegha G , Chasela CS , Jamieson DJ , van der Horst CM . AIDS 2015 29 (15) 1953-61 OBJECTIVE: The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding. DESIGN: The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was a randomized trial of 2369 mother-infant pairs conducted from 2004 to 2010. In addition to an intrapartum regimen, all mother-infant pairs were randomly assigned to three antiretroviral intervention arms during 28 weeks of breastfeeding: no further antiretroviral prophylaxis (control arm); infant-daily nevirapine (nevirapine arm); and maternal zidovudine, lamivudine and either nevirapine, nelfinavir or lopinavir-ritonavir (maternal arm). After breastfeeding cessation counselling and stopping the antiretroviral interventions by 28 weeks, 28 infant HIV infections occurred. METHODS: To determine whether these infections occurred during the breastfeeding and antiretroviral intervention phase but had delayed detection on the antiretroviral arms, we performed ultrasensitive (droplet digital PCR) HIV testing on infants with stored peripheral blood mononuclear cell (PBMC) specimens at 24 weeks (n = 9). RESULTS: Of the nine infants, all three on the infant nevirapine arm had detectable HIV DNA at 24 weeks, compared with two of four on the maternal antiretroviral arm and one of two on the control arm. For infants with detectable HIV at 24 weeks, the median delay in detection between the ultrasensitive and standard assays was 18.3 weeks for the nevirapine arm, 15.4 weeks for the maternal arm and 9.4 weeks for the control arm. CONCLUSION: The prolonged inability to detect HIV with standard assays in the context of postnatal antiretroviral prophylaxis suggests that early antiretrovirals may restrict HIV replication sufficiently to lead to missed diagnosis among infected infants. Therefore, repeat virologic testing is warranted beyond the WHO-recommended point of testing at 6 weeks after breastfeeding cessation. |
Regression analysis for differentially misclassified correlated binary outcomes
Tang L , Lyles RH , King CC , Hogan JW , Lo Y . J R Stat Soc Ser C Appl Stat 2015 64 (3) 433-449 In many epidemiological and clinical studies, misclassification may arise in one or several variables, resulting in potentially invalid analytic results (e.g. estimates of odds ratios of interest) when no correction is made. Here we consider the situation in which correlated binary response variables are subject to misclassification. Building on prior work, we provide an approach to adjust for potentially complex differential misclassification via internal validation sampling applied at multiple study time points. We seek to estimate the parameters of a primary generalized linear mixed model that accounts for baseline and/or time-dependent covariates. The misclassification process is modelled via a second generalized linear model that captures variations in sensitivity and specificity parameters according to time and a set of subject-specific covariates that may or may not overlap with those in the primary model. Simulation studies demonstrate the precision and validity of the method proposed. An application is presented based on longitudinal assessments of bacterial vaginosis conducted in the 'HIV epidemiology research' study. |
Binary regression with differentially misclassified response and exposure variables
Tang L , Lyles RH , King CC , Celentano DD , Lo Y . Stat Med 2015 34 (9) 1605-20 Misclassification is a long-standing statistical problem in epidemiology. In many real studies, either an exposure or a response variable or both may be misclassified. As such, potential threats to the validity of the analytic results (e.g., estimates of odds ratios) that stem from misclassification are widely discussed in the literature. Much of the discussion has been restricted to the nondifferential case, in which misclassification rates for a particular variable are assumed not to depend on other variables. However, complex differential misclassification patterns are common in practice, as we illustrate here using bacterial vaginosis and Trichomoniasis data from the HIV Epidemiology Research Study (HERS). Therefore, clear illustrations of valid and accessible methods that deal with complex misclassification are still in high demand. We formulate a maximum likelihood (ML) framework that allows flexible modeling of misclassification in both the response and a key binary exposure variable, while adjusting for other covariates via logistic regression. The approach emphasizes the use of internal validation data in order to evaluate the underlying misclassification mechanisms. Data-driven simulations show that the proposed ML analysis outperforms less flexible approaches that fail to appropriately account for complex misclassification patterns. The value and validity of the method are further demonstrated through a comprehensive analysis of the HERS example data. |
Dietary patterns and maternal anthropometry in HIV-infected, pregnant Malawian women
Ramlal RT , Tembo M , King CC , Ellington S , Soko A , Chigwenembe M , Chasela C , Jamieson DJ , van der Horst C , Bentley M , Adair L , The Ban Study Team . Nutrients 2015 7 (1) 584-94 Diet is a modifiable factor that can contribute to the health of pregnant women. In a sample of 577 HIV-positive pregnant women who completed baseline interviews for the Breastfeeding, Antiretrovirals, and Nutrition Study in Lilongwe, Malawi, cluster analysis was used to derive dietary patterns. Multiple regression analysis was used to identify associations between the dietary patterns and mid-upper arm circumference (MUAC), arm muscle area (AMA), arm fat area (AFA), and hemoglobin at baseline. Three key dietary patterns were identified: animal-based, plant-based, and grain-based. Women with relatively greater wealth were more likely to consume the animal-based diet, which had the highest intake of energy, protein, and fat and was associated with higher hemoglobin levels compared to the other diets. Women with the lowest wealth were more likely to consume the grain-based diet with the lowest intake of energy, protein, fat, and iron and were more likely to have lower AFA than women on the animal-based and plant-based diets, but higher AMA compared to women on the animal-based diet. Pregnant, HIV-infected women in Malawi could benefit from nutritional support to ensure greater nutrient diversity during pregnancy, when women face increased nutrient demands to support fetal growth and development. |
Reducing lost to follow-up in a large clinical trial of prevention of mother-to-child transmission of HIV: the Breastfeeding, Antiretrovirals and Nutrition study experience
Sellers CJ , Lee H , Chasela C , Kayira D , Soko A , Mofolo I , Ellington S , Hudgens MG , Kourtis AP , King CC , Jamieson DJ , van der Horst C . Clin Trials 2014 12 (2) 156-65 BACKGROUND/AIMS: Retaining patients in prevention of mother-to-child transmission of HIV studies can be challenging in resource-limited settings, where high lost to follow-up rates have been reported. In this article, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition study and analyze factors associated with lost to follow-up in the study. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition clinical trial was designed to evaluate the efficacy of three different mother-to-child HIV transmission prevention strategies. Lower than expected participant retention prompted enhanced efforts to reduce lost to follow-up during the conduct of the trial. Following study completion, we employed regression modeling to determine predictors of perfect attendance and variables associated with being lost to follow-up. RESULTS: During the study, intensive tracing efforts were initiated after the first 1686 mother-infant pairs had been enrolled, and 327 pairs were missing. Of these pairs, 60 were located and had complete data obtained. Among the 683 participants enrolling after initiation of intensive tracing efforts, the lost to follow-up rate was 3.4%. At study's end, 290 (12.2%) of the 2369 mother-infant pairs were lost to follow-up. Among successfully traced missing pairs, relocation was common and three were deceased. Log-binomial regression modeling revealed higher maternal hemoglobin and older maternal age to be significant predictors of perfect attendance. These factors and the presence of food insecurity were also significantly associated with lower rates of lost to follow-up. CONCLUSION: In this large HIV prevention trial, intensive tracing efforts centered on reaching study participants at their homes succeeded in finding a substantial proportion of lost to follow-up participants and were very effective in preventing further lost to follow-up during the remainder of the trial. The association between food insecurity and lower rates of lost to follow-up is likely related to the study's provision of nutritional support, including a family maize supplement, which may have contributed to patient retention. |
GB Virus C (GBV-C) infection in Hepatitis C Virus (HCV) seropositive women with or at risk for HIV Infection
Blackard JT , Ma G , Welge JA , King CC , Taylor LE , Mayer KH , Klein RS , Celentano DD , Sobel JD , Jamieson DJ , Gardner L . PLoS One 2014 9 (12) e114467 BACKGROUND: GB virus C (GBV-C) may have a beneficial impact on HIV disease progression; however, the epidemiologic characteristics of this virus are not well characterized. Behavioral factors and gender may lead to differential rates of GBV-C infection; yet, studies have rarely addressed GBV-C infections in women or racial/ethnic minorities. Therefore, we evaluated GBV-C RNA prevalence and genotype distribution in a large prospective study of high-risk women in the US. RESULTS: 438 hepatitis C virus (HCV) seropositive women, including 306 HIV-infected and 132 HIV-uninfected women, from the HIV Epidemiologic Research Study were evaluated for GBV-C RNA. 347 (79.2%) women were GBV-C RNA negative, while 91 (20.8%) were GBV-C RNA positive. GBV-C positive women were younger than GBV-C negative women. Among 306 HIV-infected women, 70 (22.9%) women were HIV/GBV-C co-infected. Among HIV-infected women, the only significant difference between GBV-negative and GBV-positive women was age (mean 38.4 vs. 35.1 years; p<0.001). Median baseline CD4 cell counts and plasma HIV RNA levels were similar. The GBV-C genotypes were 1 (n = 31; 44.3%), 2 (n = 36; 51.4%), and 3 (n = 3; 4.3%). The distribution of GBV-C genotypes in co-infected women differed significantly by race/ethnicity. However, median CD4 cell counts and log10 HIV RNA levels did not differ by GBV-C genotype. GBV-C incidence was 2.7% over a median follow-up of 2.9 (IQR: 1.5, 4.9) years, while GBV-C clearance was 35.7% over a median follow-up of 2.44 (1.4, 3.5) years. 4 women switched genotypes. CONCLUSIONS: Age, injection drug use, a history of sex for money or drugs, and number of recent male sex partners were associated with GBV-C infection among all women in this analysis. However, CD4 cell count and HIV viral load of HIV/HCV/GBV-C co-infected women were not different although race was associated with GBV-C genotype. |
Dense genotyping of immune-related loci identifies variants associated with clearance of HPV among HIV-positive women in the HIV epidemiology research study (HERS).
Sudenga SL , Wiener HW , King CC , Rompalo AM , Cu-Uvin S , Klein RS , Shah KV , Sobel JD , Jamieson DJ , Shrestha S . PLoS One 2014 9 (6) e99109 Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258), European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900) in the MAGI-3 gene and one SNP (rs8031627) in the SMAD3 gene were associated with HR-HPV clearance (p<10-6). A variant (rs1633038) in HLA-G were also significantly associated in African American. Results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes. |
Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants
Chasela CS , Kourtis AP , Wall P , Drobeniuc J , King CC , Thai H , Teshale EH , Hosseinipour M , Ellington S , Codd MB , Jamieson DJ , Knight R , Fitzpatrick P , Kamili S , Hoffman I , Kayira D , Mumba N , Kamwendo DD , Martinson F , Powderly W , Teo CG , van der Horst C . J Hepatol 2014 60 (3) 508-14 BACKGROUND & AIMS: The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naive, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants. METHODS: Plasma from 2048 HIV-infected, Malawian women and their infants were tested for markers of HBV infection. Study participants were provided standard-of-care health services, which included administration of pentavalent vaccine to infants at 6, 10, and 14weeks of age. RESULTS: One-hundred and three women (5%) were HBsAg-positive; 70 of these HBsAg-positive women were also HBV-DNA-positive. Sixteen women (0.8%) were HBV-DNA-positive but HBsAg-negative. Five of 51 infants (9.8%) born to HBsAg-positive and/or HBV-DNA-positive women were HBV-DNA-positive by 48weeks of age.HBV DNA concentrations of two infants of mothers who received extended lamivudine-containing anti-HIV prophylaxis were <4 log10 IU/ml compared to 8 log10 IU/ml in three infants of mothers who did not. CONCLUSIONS: HBV DNA was detected in nearly 10% of infants born to HBV/HIV-coinfected women. Antenatal testing for HIV and HBV, if instituted, can facilitate implementation of prophylactic measures against infant infection by both viruses. |
The effect of cotrimoxazole prophylactic treatment on malaria, birth outcomes, and postpartum CD4 count in HIV-infected women
Dow A , Kayira D , Hudgens MG , Van Rie A , King CC , Ellington S , Chome N , Kourtis A , Turner AN , Kacheche Z , Jamieson DJ , Chasela C , van der Horst C . Infect Dis Obstet Gynecol 2013 2013 340702 BACKGROUND: Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). METHODS: Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. RESULTS: Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (-77.6 cells/ mu L, 95% CI: -125.2, -30.1) and not receiving antiretrovirals (-33.7 cells/ mu L, 95% CI: -58.6, -8.8). CONCLUSIONS: Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination. |
Role of intestinal mucosal integrity in HIV transmission to infants through breastfeeding: the BAN Study
Kourtis AP , Ibegbu CC , Wiener J , King CC , Tegha G , Kamwendo D , Kumwenda J , Pal KS , Flax V , Ellington S , Kacheche Z , Kayira D , Chasela C , van der Horst C , Jamieson DJ . J Infect Dis 2013 208 (4) 653-61 BACKGROUND: Increased intestinal permeability may be one of the mechanisms of transmission of HIV to the infant through breastfeeding. It correlates with microbial translocation, which can be measured through quantification of bacterial lipopolysaccharide (LPS). METHODS: We evaluated levels of plasma LPS (Limulus Amoebocyte Lysate assay), and immune activation markers in serial specimens of HIV-exposed uninfected and HIV-infected infants from the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study. RESULTS: Plasma LPS levels increased after infants in BAN weaned from the breast at 24 weeks of age. Cotrimoxazole prophylaxis was associated with higher plasma LPS levels (p=0.004). Infants with HIV infection had higher LPS levels compared with uninfected infants (p= 0.004). Pre-infection plasma LPS levels were a significant predictor of infant HIV infection through breastfeeding (HR=1.60 for every unit increase in plasma LPS, p=0.01) and for lower infant length-for-age (p=0.02). CONCLUSIONS: These findings suggest that disruption in intestinal integrity is a mechanism of HIV transmission to the infant through breastfeeding. Weaning from breast milk and use of antibiotic prophylaxis was associated with increased levels of microbial translocation, which could facilitate HIV entry through the intestine. Complementary approaches to enhance intestinal mucosal integrity in the infant may further reduce breastfeeding transmission of HIV. |
Patterns of body composition among HIV-infected, pregnant Malawians and the effects of famine season
Ramlal RT , Tembo M , Soko A , Chigwenembe M , Tohill BC , Kayira D , King CC , Chasela C , Jamieson D , van der Horst C , Bentley ME , Adair LS . Matern Child Health J 2013 17 (2) 265-73 We describe change in weight, midupper arm circumference (MUAC), arm muscle area (AMA) and arm fat area (AFA) in 1130 pregnant HIV-infected women with CD4 counts > 200 as part of the BAN Study ( www.thebanstudy.org ), a randomized, controlled clinical trial to evaluate antiretroviral and nutrition interventions to reduce mother-to-child transmission of HIV during breast feeding. In a longitudinal analysis, we found a linear increase in weight with a mean rate of weight gain of 0.27 kgs/week, from baseline (12 to 30 weeks gestation) until the last follow-up visit (32-38 weeks). Analysis of weight gain showed that 17.1% of the intervals between visits resulted in a weight loss. In unadjusted models, MUAC and AMA increased and AFA declined during late pregnancy. Based on multivariable regression analysis, exposure to the famine season resulted in larger losses in AMA [-0.08, 95% CI -0.14, -0.02; p = 0.01] while AFA losses occurred irrespective of season [-0.55, 95%: -0.95, -0.14, p = 0.01]. CD4 was associated with AFA [0.21, 95% CI 0.01, 0.41, p = .04]. Age was positively associated with MUAC and AMA. Wealth was positively associated with MUAC, AFA, and weight. While patterns of anthropometric measures among HIV-infected, pregnant women were found to be similar to those reported for uninfected women in sub-Saharan Africa, effects of the famine season among undernourished, Malawian women are of concern. Strategies to optimize nutrition during pregnancy for these women appear warranted. |
The role of co-infections in mother-to-child transmission of HIV
King CC , Ellington SR , Kourtis AP . Curr HIV Res 2012 11 (1) 10-23 In HIV-infected women, co-infections that target the placenta, fetal membranes, genital tract, and breast tissue, as well as systemic maternal and infant infections, have been shown to increase the risk for mother-to-child transmission of HIV (MTCT). Active co-infection stimulates the release of cytokines and inflammatory agents that enhance HIV replication locally or systemically and increase tissue permeability, which weakens natural defenses to MTCT. Many maternal or infant co-infections can affect MTCT of HIV, and particular ones, such as genital tract infection with herpes simplex virus, or systemic infections such as hepatitis B, can have substantial epidemiologic impact on MTCT. Screening and treatment for co-infections that can make infants susceptible to MTCT in utero, peripartum, or postpartum can help reduce the incidence of HIV infection among infants and improve the health of mothers and infants worldwide. |
Tenofovir use and renal insufficiency among pregnant and general adult population of HIV-infected, ART-naive individuals in Lilongwe, Malawi
Johnson DC , Chasela C , Maliwichi M , Mwafongo A , Akinkuotu A , Moses A , Jamieson DJ , Kourtis AP , King CC , van der Horst C , Hosseinipour MC . PLoS One 2012 7 (7) e41011 BACKGROUND: The Malawian government recently changed its prevention of mother-to-child transmission (PMTCT) regimen and plans to change its first-line antiretroviral therapy (ART) regimen to Tenofovir(TDF)/Lamivudine/Efavirenz as a fixed-dose combination tablet. Implementation could be challenging if baseline creatinine clearance (CrCl) screening were required to assess renal function prior to TDF therapy. Our goal is to determine predictors of CrCl<50 ml/min among HIV-infected, ART-naive individuals. METHODOLOGY: Data on HIV-infected, ART-naive adults screened for enrollment into 5 HIV clinical trials in Lilongwe, Malawi were combined for a pooled analysis of predictors for CrCl<50 ml/min. CrCl was derived from the Cockroft-Gault equation. Multivariable logistic regression modeled the association of age, body mass index (BMI), hemoglobin, CD4 cell count <350 cells/mm(3), gender, and pregnancy with CrCl<50 ml/min. RESULTS: The analysis included 3508 patients with values for creatinine clearance. Most subjects were female (90.6%) with a median age of 26 years (IQR 22-29). The median CD4 cell count was 444 (IQR 298.0-561.0), and 85.2% percent of women in our study were pregnant. Few patients had CrCl<50 ml/min (n = 38, 1.1%). A BMI less than 18.5 in non-pregnant females (OR = 8.87, 95% CI = 2.45-32.09)) was associated with CrCl<50 ml/min. Hemoglobin level higher than 10 g/dL in males (OR = 0.69, 95% CI = 0.56-0.86) and non-pregnant females (OR = 0.21, 95% CI = 0.04-0.97) was protective against CrCl<50 ml/min. DISCUSSION: Our findings indicate few patients would be excluded from a TDF-based antiretroviral regimen, suggesting baseline creatinine clearance assessment may not be necessary for implementation. However, in ART settings individuals with low BMI or anemia could potentially be at increased risk for lower CrCl. |
Prevalence of hepatitis C virus infection among human immunodeficiency virus-1-infected pregnant women in Malawi: the BAN study
Chasela CS , Wall P , Drobeniuc J , King CC , Teshale E , Hosseinipour MC , Ellington SR , Codd M , Jamieson DJ , Knight RJ , Fitzpatrick P , Kourtis AP , Hoffman IF , Kayira D , Mumba N , Kamwendo DD , Martinson F , Powderly W , van der Horst C , Kamili S . J Clin Virol 2012 54 (4) 318-320 BACKGROUND: In Sub-Saharan Africa, prevalence estimates of hepatitis C virus (HCV) vary widely. OBJECTIVES: To assess the prevalence of HCV infection among HIV-infected, pregnant women screened for a large clinical trial in Lilongwe, Malawi. STUDY DESIGN: Plasma from 2041 HIV-infected, pregnant women was screened for anti-HCV IgG using a chemiluminiscent immunometric assay (CIA). Specimens with a signal-cut-off ratio≥1.00 were considered reactive and those with S/Co ratio<1.00 non-reactive. All CIA-reactive specimens were tested by a recombinant immunoblot assay (RIBA) for anti-HCV and by PCR for HCV RNA. RESULTS: Of 2041 specimens, 110 (5.3%, 95% CI: 4.5-6.5%) were CIA reactive. Of the 109 CIA reactive specimens available for RIBA testing, 2 (1.8%) were positive, 28 (25.7%) were indeterminate, and 79 (72.5%) were negative. All CIA-reactive specimens were HCV RNA negative (n=110). The estimated HCV prevalence based on the screening assay alone was 5.3%; based on supplemental RIBA testing, the status of HCV infection remained indeterminate in 1.4% (28/2040, 95% CI: 0.1-2.0) and the prevalence of confirmed HCV infections was 0.1% (2/2040, 95% CI: 0-0.4%). CONCLUSIONS: HCV seroprevalence among HIV-infected, pregnant women in Malawi confirmed by supplemental RIBA HCV 3.0 is low (0.1%); CIA showed a high false-reactivity rate in this population. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 06, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure