Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 42 Records) |
Query Trace: Kayira D[original query] |
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Examining teen club attendance and viral load suppression among adolescents under differentiated HIV care in Malawi: a sub-optimal scenario
Chamanga R , Musukwa T , Kalitera L , Gent F , Nkhoma H , Kudiabor K , Maida A , Kayira D , Buie V , Woelk G , Maphosa T . BMC Public Health 2024 24 (1) 3605 BACKGROUND: In Malawi, compared to adults, adolescents have higher rates of high HIV viremia and poorer antiretroviral therapy (ART) outcomes. The Ministry of Health, supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF), implemented the provision of differentiated care clubs for adolescents living with HIV (ALHIV), called "teen clubs," to provide psychosocial support and an HIV care package to improve clinical outcomes. We evaluated teen club attendance and factors associated with unsuppressed viral load (VL) in ALHIV enrolled in these teen clubs. METHODS: This cross-sectional study used program data from 35 health facilities in four districts that offered teen club services. We enrolled all ALHIV receiving ART ages 10-19 years who attended teen clubs between July 2018- September 2019 and had documented viral load results. Unsuppressed VL was defined as HIV RNA = > 1000 copies/mL, and optimal ART adherence was defined as having an expected pill count suggesting that between 95 and 105% of pills prescribed were consumed. We used multivariable logistic regression to identify factors associated with unsuppressed VL, adjusting for sex, age, education, district, adherence assessment, disclosure of one's HIV status, and teen club attendance. RESULTS: Our analysis included 1,162 ALHIV with a median age of 15 years (IQR 13-17). The majority were female (n = 614, 53%) and attended one or two teen club visits (n = 665, 57%). Unsuppressed VL was identified in 28% of ALHIV. ALHIV with sub-optimal ART adherence were twice as likely to have unsuppressed VL (adjusted odds ratio [aOR] 2.0, 95% confidence interval (CI): 1.42-2.62) compared to those with optimal ART adherence. ALHIV on second-line treatments, were nearly four times more likely to have unsuppressed VL (aOR 3.7, 95% CI: 1.64-9.09) compared with those on first-line ART. ALHIV who had attained secondary school education were less likely to have unsuppressed VL (aOR 0.42, 95% CI 0.21-0.81) than those who only attained primary school education. CONCLUSION: Even amongst adolescents enrolled in teen clubs, teen club attendance is low and high HIV viremia prevails. A continual focus on adolescents is needed to promote consistent teen club attendance and consistent ART adherence among the adolescents enrolled in differentiated service delivery. |
Mortality among children under five years of age living with HIV on antiretroviral treatment from HIV case surveillance data, Malawi, 2022
Chapman KS , Luhanga M , Mtonga G , Agathis N , Kayira D , Hrapcak S , Patel M , Kress H , Arons M . Pediatr Infect Dis J 2024 From Malawi's HIV case surveillance, we report clinical characteristics and outcomes of 4461 children living with HIV on antiretroviral treatment aged <5 years from January to December, 2022. Among the 4% of children living with HIV who died, 43% were asymptomatic, 35% had advanced or severe symptoms at the time of HIV diagnosis and 50% died within 6 months of receiving an HIV diagnosis. |
Characteristics of TPT initiation and completion among people living with HIV
Gunde L , Wang A , Payne D , O'Connor S , Kabaghe A , Kalata N , Maida A , Kayira D , Buie V , Tauzi L , Sankhani A , Thawani A , Rambiki E , Ahimbisibwe A , Maphosa T , Kudiabor K , Nyirenda R , Mpunga J , Mbendera K , Nyasulu P , Kayigamba F , Farahani M , Voetsch AC , Brown K , Jahn A , Girma B , Mirkovic K . IJTLD Open 2024 1 (1) 11-19 BACKGROUND: TB preventive treatment (TPT) reduces morbidity and mortality among people living with HIV (PLHIV). Despite the successful scale-up of TPT in Malawi, monitoring and evaluation have been suboptimal. We utilized the Malawi Population-Based HIV Impact Assessment (MPHIA) 2020-2021 survey data to estimate TPT uptake and completion among self-reported HIV-positive persons. METHODS: We estimated the proportion of HIV-positive respondents who had ever undergone TPT, and determined the percentage of those currently on TPT who had completed more than 6 months of treatment. Bivariate and multivariable logistic regression were performed to calculate the odds ratios for factors associated with ever-taking TPT. All variables were self-reported, and the analysis was weighted and accounted for in the survey design. RESULTS: Of the HIV+ respondents, 38.8% (95% CI 36.4-41.3) had ever taken TPT. The adjusted odds of ever taking TPT were 8.0 and 5.2 times as high in the Central and Southern regions, respectively, compared to the Northern region; 1.9 times higher among those in the highest wealth quintile, and 2.1 times higher for those on antiretroviral therapy >10 years. Of those currently taking TPT, 56.2% completed >6 months of TPT. CONCLUSION: These results suggest low TPT uptake and >6 months' completion rates among self-reported HIV+ persons. Initiatives to create demand and strengthen adherence would improve TPT uptake. |
Unlocking the potential: exploring the impact of dolutegravir treatment on body mass index improvement in underweight adults with HIV in Malawi
Maphosa T , Dunga S , Makonokaya L , Woelk G , Maida A , Wang A , Ahimbisibwe A , Chamanga RK , Zimba SB , Kayira D , Machekano R . BMC Public Health 2024 24 (1) 1321 BACKGROUND: The introduction of dolutegravir (DTG) in treating HIV has shown enhanced efficacy and tolerability. This study examined changes in weight gain and body mass index (BMI) at 6- and 12-months after post-initiating antiretroviral therapy (ART), comparing people living with HIV (PLHIV) on DTG-based regimens with those on non-DTG-based regimens in Malawi. METHODS: Retrospective cohort data from 40 public health facilities in Malawi were used, including adult ART patients (aged ≥ 15 years) from January 2017 to March 2020. The primary outcomes were BMI changes/transitions, with secondary outcomes focused on estimating the proportion of mean weight gain > 10% post-ART initiation and BMI category transitions. Descriptive statistics and binomial regression were used to estimate the unadjusted and adjusted relative risks (RR) of weight gain of more than ( >) 10%. RESULTS: The study included 3,520 adult ART patients with baseline weight after ART initiation, predominantly female (62.7%) and aged 25-49 (61.1%), with a median age of 33 years (interquartile range (IQR), 23-42 years). These findings highlight the influence of age, ART history, and current regimen on weight gain. After 12months follow up, compared to those aged 15-24 years, individuals aged 25-49 had an Adjusted RR (ARR) of 0.5 (95% Confidence Interval (CI): 0.35-0.70), suggesting a 50% reduced likelihood of > 10% weight gain after post-ART initiation. Similarly, those aged 50 + had an ARR of 0.33 (95% CI: 0.20-0.58), indicating a 67% decreased likelihood compared to the youngest age group 15-24 years. This study highlights the positive impact of DTG-based regimens, revealing significant transitions from underweight to normal BMI categories at 6- and 12-months post-initiation. CONCLUSION: This study provides insights into weight gain patterns in patients on DTG-based regimens compared with those on non-DTG regimens. Younger individuals (15-24 years) exhibited higher odds of weight gain, suggesting a need for increased surveillance in this age group. These findings contribute to the understanding DTG's potential effects on weight gain, aiding clinical decision making. Further research is required to comprehensively understand the underlying mechanisms and long-term implications of weight gain in patients receiving DTG-based regimens. |
Early effects of scaling up dolutegravir-based arv regimens among children living with HIV in Malawi
Makonokaya L , Maida A , Kalitera LU , Wang A , Kapanda L , Kayira D , Bottoman M , Nkhoma H , Dunga S , Joaki Z , Chamanga R , Nkanaunena K , Hrapcak S , Nyirenda R , Chiwandira B , Maulidi M , Woelk G , Machekano R , Maphosa T . AIDS Behav 2024 Viral suppression (VS) in children has remained suboptimal compared to that in adults. We evaluated the impact of transitioning children weighing < 20 kg to a pediatric formulation of dolutegravir (pDTG) on VS in Malawi. We analyzed routine retrospective program data from electronic medical record systems pooled across 169 healthcare facilities in Malawi supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). We included children who weighed < 20 kg and received antiretroviral therapy (ART) between July 2021-June 2022. Using descriptive statistics, we summarized demographic and clinical characteristics, ART regimens, ART adherence, and VS. We used logistic regression to identify factors associated with post-transition VS. A total of 2468 Children Living with HIV (CLHIV) were included, 55.3% of whom were < 60 months old. Most (83.8%) had initiated on non-DTG-based ART; 71.0% of these had a viral load (VL) test result before transitioning to pDTG, and 62.5% had VS. Nearly all (99.9%) CLHIV transitioned to pDTG-based regimens. Six months after the transition, 52.7% had good ART adherence, and 38.6% had routine VL testing results; 81.7% achieved VS. Post-transition VS was associated with good adherence and pre-transition VS: adjusted odds ratios of 2.79 (95% CI 1.65-4.71), p < 0.001 and 5.32 (95% CI 3.23-9.48), p < 0.001, respectively. After transitioning to pDTG, VS was achieved in most children tested within the first 6 months. However, adherence remained suboptimal post-transition and VL testing at 6 months was limited. Interventions to improve VL testing and enhance ART adherence are still needed in CLHIV on pDTG-based regimens. |
Impact of HIV treat-all and complementary policies on ART linkage in 13 PEPFAR-supported African countries
Russell A , Verani AR , Pals S , Reagon VM , Alexander LN , Galloway ET , Mange MM , Kalimugogo P , Nyika P , Fadil YM , Aoko A , Asiimwe FM , Ikpeazu A , Kayira D , Letebele M , Maida A , Magesa D , Mutandi G , Mwila AC , Onotu D , Nkwoh KT , Wangari E . BMC Health Serv Res 2023 23 (1) 1151 BACKGROUND: In 2015, the World Health Organization recommended that all people living with HIV begin antiretroviral treatment (ART) regardless of immune status, a policy known as 'Treat-All to end AIDS', commonly referred to as Treat-All. Almost all low- and middle-income countries adopted this policy by 2019. This study describes how linkage to treatment of newly diagnosed persons changed between 2015 and 2018 and how complementary policies may have similarly increased linkage for 13 African countries. These countries adopted and implemented Treat-All policies between 2015 and 2018 and were supported by the U.S. Government's President's Emergency Plan for AIDS Relief (PEPFAR). The focuses of this research were to understand 1) linkage rates to ART initiation before and after the adoption of Treat-All in each country; 2) how Treat-All implementation differed across these countries; and 3) whether complementary policies (including same-day treatment initiation, task-shifting, reduced ART visits, and reduced ART pickups) implemented around the same time may have increased ART linkage. METHODS: HIV testing and treatment data were collected by PEPFAR country programs in 13 African countries from 2015 to 2018. These countries were chosen based on the completeness of policy data and availability of program data during the study period. Program data were used to calculate proxy linkage rates. These rates were compared relative to the Treat All adoption period and the adoption of complementary policies. RESULTS: The 13 countries experienced an average increase in ART linkage of 29.3% over the entire study period. In examining individual countries, all but two showed increases in linkage to treatment immediately after Treat All adoption. Across all countries, those that had adopted four or more complementary policies showed an average increased linkage of 39.8% compared to 13.9% in countries with fewer than four complementary policies. CONCLUSIONS: Eleven of 13 country programs examined in this study demonstrated an increase in ART linkage after Treat-All policy adoption. Increases in linkage were associated with complementary policies. When exploring new public health policies, policymakers may consider which complementary policies might also help achieve the desired outcome of the public health policy. |
Acceptability and usability of a paediatric HIV screening tool in high-volume outpatient settings in Malawi, perspectives from caregivers and healthcare workers
Katirayi L , Maphosa T , Kudiabor K , Kayira D , Gross J , Hrapcak S , Chamanga R , Nkhoma H , Puleni P , Maida A , Ahimbisibwe A , Woelk G . BMJ Paediatr Open 2023 7 (1) BACKGROUND: Using an HIV pretest screening tool to identify children most at risk for HIV infection may be a more efficient and cost-effective approach to identify children living with HIV in resource-limited settings. These tools seek to reduce overtesting of children by increasing the positive predictive value while ensuring a high negative predictive value for those screened for HIV. METHODS: This qualitative study in Malawi evaluated acceptability and usability of a modified version of the Zimbabwe HIV screening tool to identify children aged 2-14 years most-at-risk. The tool included additional questions about previous hospitalisations due to malaria and prior documented diagnoses. Sixteen interviews were conducted with expert clients (ECs), trained peer-supporters, which administered the screening tool and 12 interviews with biological and non-biological caregivers of screened children. All interviews were audiorecorded, transcribed and translated. Transcripts were analysed manually using a short-answer analysis, compiling responses for each question by study participant group. Summary documents were generated, identifying common and outlier perspectives. RESULTS: The HIV paediatric screening tool was generally accepted by caregivers and ECs, with both groups seeing the benefit of the tool and promoting its use. The ECs who were primarily responsible for implementing the tool initially struggled with acceptance of the tool but started to accept it after additional training and mentorship was provided. Overall, caregivers accepted having their children tested for HIV, although non-biological caregivers expressed hesitancy in giving consent for HIV testing. ECs reported challenges with the ability for non-biological caregivers to answer some questions. CONCLUSION: This study found general acceptance of paediatric screening tools in children in Malawi and identified some minor challenges that raise important considerations for tool implementation. These include the need for a thorough orientation of the tools for the healthcare workers and caregivers, appropriate space at the facility, and adequate staffing and commodities. |
HIV viral load scale-up among children and adolescents: Trends in viral load suppression, sample type and processing in 7 PEPFAR countries, 2015-2018
Hrapcak S , Pals S , Itoh M , Peters N , Carpenter D , Hackett S , Prao AK , Adje-Toure C , Eboi E , Mutisya I , Nyabiage Omoto L , Ondondo RO , Bowen N , Nyanya W , Kayira D , Kaba MD , Mwenda R , Deus MI , Almeida J , Cuco RMM , Boylan A , Beard S , Ashikoto S , van Rooyen G , Kindra G , Diallo K , Carmona S , Nazziwa E , Mwangi C , Ntale J , Ssewanyana I , Nabadda SN , Nabukenya M , Ellenberger D , Rivadeneira E . Pediatr Infect Dis J 2023 42 (4) e102-e104 HIV-positive children and adolescents face gaps in viral load (VL) testing. To understand trends in pediatric/adolescent VL testing, 7 countries collected data from Laboratory Information Management Systems. Results showed increasing proportion of VL tests done through dried blood spot (DBS) and decreased sample rejection rates for DBS compared with plasma, supporting use of DBS VL when skilled phlebotomy is unavailable. |
Toward elimination of mother-to-child transmission of HIV in Malawi: Findings from the Malawi Population-based HIV Impact Assessment (2015-2016)
Kim E , Jonnalagadda S , Cuervo-Rojas J , Jahn A , Payne D , West C , Ogollah F , Maida A , Kayira D , Nyirenda R , Dobbs T , Patel H , Radin E , Voetsch A , Auld A . PLoS One 2022 17 (9) e0273639 BACKGROUND: Malawi spearheaded the development and implementation of Option B+ for prevention of mother-to-child transmission of HIV (PMTCT), providing life-long ART for all HIV-positive pregnant and breastfeeding women. We used data from the 2015-2016 Malawi Population-based HIV Impact Assessment (MPHIA) to estimate progress toward 90-90-90 targets (90% of those with HIV know their HIV-positive status; of these, 90% are receiving ART; and of these, 90% have viral load suppression [VLS]) for HIV-positive women reporting a live birth in the previous 3 years. METHODS: MPHIA was a nationally representative household survey; consenting eligible women aged 15-64 years were interviewed on pregnancies and outcomes, including HIV status during their most recent pregnancy, PMTCT uptake, and early infant diagnosis (EID) testing. Descriptive analyses were weighted to account for the complex survey design. Viral load (VL) results were categorized by VLS (<1,000 copies/mL) and undetectable VL (target not detected/below the limit of detection). RESULTS: Of the 3,153 women included in our analysis, 371 (10.1%, 95% confidence interval [CI]: 8.8%-11.3%) tested HIV positive in the survey. Most HIV-positive women (84.2%, 95% CI: 79.9%-88.6%) reported knowing their HIV-positive status; of these, 94.9% (95% CI: 91.7%-98.2%) were receiving ART; and of these, 91.2% (95% CI: 87.4%-95.0%) had VLS. Among the 371 HIV-positive women, 76.0% (95% CI: 70.4%-81.7%) had VLS and 66.5% (95% CI: 59.8%-73.2%) had undetectable VL. Among 262 HIV-exposed children, 50.8% (95% CI: 42.8%-58.8%) received EID testing within 2 months of birth, whereas 17.9% (95% CI: 11.9%-23.8%) did not receive EID testing. Of 190 HIV-exposed children with a reported HIV test result, 2.1% (95% CI: 0.0%-4.6%) had positive results. CONCLUSIONS: MPHIA data demonstrate high PMTCT uptake at a population level. However, our results identify some gaps in VLS in postpartum women and EID testing. |
Uninterrupted HIV treatment for women: Policies and practices for care transitions during pregnancy and breastfeeding in Cte d'Ivoire, Lesotho and Malawi
Phillips TK , Olsen H , Teasdale CA , Geller A , Ts'oeu M , Buono N , Kayira D , Ngeno B , Modi S , Abrams EJ . PLoS One 2021 16 (12) e0260530 Transitions between services for continued antiretroviral treatment (ART) during and after pregnancy are a commonly overlooked aspect of the HIV care cascade, but ineffective transitions can lead to poor health outcomes for women and their children. In this qualitative study, we conducted interviews with 15 key stakeholders from Ministries of Health along with PEPFAR-supported and other in-country non-governmental organizations actively engaged in national programming for adult HIV care and prevention of mother-to-child-transmission of HIV (PMTCT) services in Côte d'Ivoire, Lesotho and Malawi. We aimed to understand perspectives regarding transitions into and out of PMTCT services for continued ART. Thematic analysis revealed that, although transitions of care are necessary and a potential point of loss from ART care in all three countries, there is a lack of clear guidance on transition approach and no formal way of monitoring transition between services. Several opportunities were identified to monitor and strengthen transitions of care for continued ART along the PMTCT cascade. |
Opportunities for closing the gap in HIV diagnosis, treatment, and viral load suppression in children in Malawi: Results from a 2015-2016 population-based HIV Impact Assessment Survey
Jonnalagadda S , Auld A , Jahn A , Saito S , Bello G , Sleeman K , Ogollah FM , Cuervo-Rojas J , Radin E , Kayira D , Kim E , Payne D , Burnett J , Hrapcak S , Patel H , Voetsch AC . Pediatr Infect Dis J 2021 40 (11) 1011-1018 BACKGROUND: Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015-2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression. METHODS: In half of the surveyed households, children ages ≥18 months to <15 years were tested using the national HIV rapid test algorithm. Children ≤18 months reactive by the initial rapid test underwent HIV total nucleic acid polymerase chain reaction confirmatory testing. Blood from HIV-positive children was tested for viral load (VL) and presence of antiretroviral drugs. HIV diagnosis and antiretroviral treatment (ART) use were defined using guardian-reporting or antiretroviral detection. RESULTS: Of the 6166 children tested, 99 were HIV-positive for a prevalence of 1.5% (95% confidence intervals [CI]: 1.1-1.9) and 8.0% (95% CI: 5.6-10.5) among HIV-exposed children. The prevalence of 1.5% was extrapolated to a national estimate of 119,501 (95% CI: 89,028-149,974) children living with HIV (CLHIV), of whom, 30.7% (95% CI: 20.3-41.1) were previously undiagnosed. Of the 69.3% diagnosed CLHIV, 86.1% (95% CI: 76.8-95.6) were on ART and 57.9% (95% CI: 41.4-74.4) of those on ART had suppressed VL (<1000 HIV RNA copies/mL). Among all CLHIV, irrespective of HIV diagnosis or ART use, 57.7% (95% CI: 45.0-70.5) had unsuppressed VL. CONCLUSIONS: Critical gaps in HIV diagnosis in children persist in Malawi. The large proportion of CLHIV with unsuppressed VL reflects gaps in diagnosis and need for more effective first- and second-line ART regimens and adherence interventions. |
Evaluating the effect of a community score card among pregnant and breastfeeding women living with HIV in two districts in Malawi
Kays M , Woelk G , Callahan T , Katirayi L , Montandon M , Chauwa F , Laterra A , Sampathkumar V , Kayira D , Kalua T , Kazemi E , Hoffman H , Modi S . PLoS One 2021 16 (8) e0255788 Malawi faces challenges with retaining women in prevention of mother-to-child HIV transmission (PMTCT) services. We evaluated Cooperative for Assistance and Relief Everywhere, Inc. (CARE's) community score card (CSC) in 11 purposively selected health facilities, assessing the effect on: (1) retention in PMTCT services, (2) uptake of early infant diagnosis (EID), (3) collective efficacy among clients, and (4) self-efficacy among health care workers (HCWs) in delivering quality services. The CSC is a participatory community approach. In this study, HCWs and PMTCT clients identified issues impacting PMTCT service quality and uptake and implemented actions for improvement. A mixed-methods, pre- and post-intervention design was used to evaluate the intervention. We abstracted routine clinical data on retention in PMTCT services for HIV-positive clients attending their first antenatal care visit and EID uptake for their infants for 8-month periods before and after implementation. To assess collective efficacy and self-efficacy, we administered questionnaires and conducted focus group discussions (FGDs) pre- and post-intervention with PMTCT clients recruited from CSC participants, and HCWs providing HIV care from facilities. Retention of HIV-positive women in PMTCT services at three and six months and EID uptake was not significantly different pre- and post-implementation. For the clients, the collective efficacy scale average improved significantly post-intervention, (p = 0.003). HCW self-efficacy scale average did not improve. Results from the FGDs highlighted a strengthened relationship between HCWs and PMTCT clients, with clients reporting increased satisfaction with services. However, the data indicated continued challenges with stigma and fear of disclosure. While CSC may foster mutual trust and respect between HCWs and PMTCT clients, we did not find it improved PMTCT retention or EID uptake within the short duration of the study period. More research is needed on ways to improve service quality and decrease stigmatized behaviors, such as HIV testing and treatment services, as well as the longer-term impacts of interventions like the CSC on clinical outcomes. |
Bringing women's voices to PMTCT CARE: adapting CARE's Community Score Card to engage women living with HIV to build quality health systems in Malawi
Laterra A , Callahan T , Msiska T , Woelk G , Chowdhary P , Gullo S , Mwale PM , Modi S , Chauwa F , Kayira D , Kalua T , Wako E . BMC Health Serv Res 2020 20 (1) 679 BACKGROUND: Coverage of prevention of mother-to-child transmission of HIV (PMTCT) services has expanded rapidly but approaches to ensure service delivery is patient-centered have not always kept pace. To better understand how the inclusion of women living with HIV in a collective, quality improvement process could address persistent gaps, we adapted a social accountability approach, CARE's Community Score Card© (CSC), to the PMTCT context. The CSC process generates perception-based score cards and facilitates regular quality improvement dialogues between service users and service providers. METHODS: Fifteen indicators were generated by PMTCT service users and providers as part of the CSC process. These indicators were scored by each population during three sequential cycles of the CSC process which culminates in a sharing of scores in a collective meeting followed by action planning. We aggregated these scores across facilities and analyzed the differences in first and last scorings to understand perceived improvements over the course of the project (z-test comparing the significance of two proportions; one-tailed p-value ≤ .05). Data were collected over 12 months from September 2017 to August 2018. RESULTS: Fourteen of the fifteen indicators improved over the course of this project, with eight showing statistically significant improvement. Out of the indicators that showed statistically significant improvement, the majority fell within the control of local communities, local health facilities, or service providers (7 out of 8) and were related to patient or user experience and support from families and community members (6 out of 8). From first to last cycle, scores from service users' and service providers' perspectives converged. At the first scoring cycle, four indicators exhibited statistically significant differences (p-value ≤ .05) between service users and service providers. At the final cycle there were no statistically significant differences between the scores of these two groups. CONCLUSIONS: By creating an opportunity for mothers living with HIV, health service providers, communities, and local government officials to jointly identify issues and implement solutions, the CSC contributed to improvements in the perceived quality of PMTCT services. The success of this model highlights the feasibility and importance of involving people living with HIV in quality improvement and assurance efforts. TRIAL REGISTRATION: Trial registration: ClincalTrials.gov NCT04372667 retrospectively registered on May 1st 2020. |
Prescription of antibacterial drugs for HIV-exposed, uninfected infants, Malawi, 2004-2010
Ewing AC , Davis NL , Kayira D , Hosseinipour MC , van der Horst C , Jamieson DJ , Kourtis AP . Emerg Infect Dis 2019 25 (1) 103-12 Antimicrobial drug resistance is a serious health hazard driven by overuse. Administration of antimicrobial drugs to HIV-exposed, uninfected infants, a population that is growing and at high risk for infection, is poorly studied. We therefore analyzed factors associated with antibacterial drug administration to HIV-exposed, uninfected infants during their first year of life. Our study population was 2,152 HIV-exposed, uninfected infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition study in Lilongwe, Malawi, during 2004-2010. All infants were breastfed through 28 weeks of age. Antibacterial drugs were prescribed frequently (to 80% of infants), and most (67%) of the 5,329 prescriptions were for respiratory indications. Most commonly prescribed were penicillins (43%) and sulfonamides (23%). Factors associated with lower hazard for antibacterial drug prescription included receipt of cotrimoxazole preventive therapy, receipt of antiretroviral drugs, and increased age. Thus, cotrimoxazole preventive therapy may lead to fewer prescriptions for antibacterial drugs for these infants. |
Co-trimoxazole prophylaxis, asymptomatic malaria parasitemia, and infectious morbidity in HIV-exposed uninfected infants in Malawi: The BAN study
Davis NL , Wiener J , Juliano JJ , Adair L , Chasela CS , Kayira D , Hudgens MG , van der Horst C , Jamieson DJ , Kourtis AP . Clin Infect Dis 2017 65 (4) 575-580 Background: HIV-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear. Methods: We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of 1) CPT and 2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6-36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEI) at 8 weeks of age (n=1984) were included when CPT was the exposure. A subset of HEI (n=471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity. Results: CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.60-0.69) and a 41% reduction in diarrheal morbidity (HR 0.59, 95% CI 0.54-0.65). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR 1.40, 95% CI 1.13-1.74) and a 50% increase in diarrheal morbidity (HR 1.50, 95% CI 1.09-2.06), after adjusting for CPT. Conclusion: CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings. |
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. |
Maternal and Breastmilk Viral Load: Impacts of Adherence on Peripartum HIV Infections Averted-The Breastfeeding, Antiretrovirals, and Nutrition Study.
Davis NL , Miller WC , Hudgens MG , Chasela CS , Sichali D , Kayira D , Nelson JA , Fiscus SA , Tegha G , Kamwendo DD , Rigdon J , Stringer JS , Juliano JJ , Ellington SR , Kourtis AP , Jamieson DJ , Van Der Horst C . J Acquir Immune Defic Syndr 2016 73 (5) 572-580 ![]() ![]() BACKGROUND: Antiretroviral interventions are used to reduce HIV viral replication and prevent mother-to-child transmission. Viral suppression relies on adherence to antiretrovirals. METHODS: A two-phase study was conducted using data from the Breastfeeding, Antiretrovirals and Nutrition study. We included mothers randomized to 28 weeks of postpartum antiretrovirals with ≥1 plasma or breastmilk specimen. All mothers who transmitted HIV to their infants from 2-28 weeks (n=31) and 15% of mothers who did not (n=232) were included. Adherence was measured by pill count [categorized as poor (0-80%), partial (81-98%) and near perfect (>98%)]. Associations between adherence and breastmilk RNA were assessed using mixed effects models. Cox models were used to estimate associations between breastmilk RNA and HIV transmission. Using Monte Carlo simulation, we estimated the number of transmissions that would occur had everyone randomized to maternal ARVs been 90% and 100% adherent. RESULTS: Partial or near perfect antiretroviral adherence significantly reduced the odds of having detectable (≥40 copies/ml) breastmilk RNA, compared to poor adherence (OR 0.23, 95% CI 0.08-0.67; OR 0.36, 95% CI 0.16-0.81, respectively). Detectable breastmilk RNA was associated with increased breastmilk transmission, compared to undetectable breastmilk RNA (HR 3.8, 95% CI 1.2-12.1). All transmitting mothers had ≥1 plasma viral load specimen >100 copies/ml. An estimated similar number of transmissions would occur with 90% adherence compared with 100%. CONCLUSIONS: Helping patients adhere to antiretrovirals throughout breastfeeding is important for realizing the full potential of recommended antiretroviral interventions to prevent mother-to-child HIV transmission. Maintaining plasma viral load <100 copies/ml may prevent breastmilk transmission. |
Cytomegalovirus IgG level and avidity in breastfeeding infants of HIV-infected mothers in Malawi
Kourtis AP , Wiener J , Chang TS , Dollard SC , Amin MM , Ellington S , Kayira D , van der Horst C , Jamieson DJ . Clin Vaccine Immunol 2015 22 (12) 1222-6 BACKGROUND: Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated results with presence of detectable CMV DNA in the blood. METHODS: The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither, for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth, 24 and 48 weeks of age. RESULTS: Ninety four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infection. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infection. Taken together, the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG, most of them (70.9%) of high avidity. CONCLUSIONS: CMV serology and avidity testing, combined with PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. CMV PCR in the blood detected most, but not all infant CMV infections. |
Frequent nevirapine resistance in infants infected by HIV-1 via breastfeeding while on nevirapine prophylaxis: results of the Breastfeeding, Antiretrovirals and Nutrition study
Nelson JA , Fokar A , Hudgens MG , Compliment KJ , Hawkins JT , Tegha G , Kamwendo DD , Kayira D , Mofolo IA , Kourtis AP , Jamieson DJ , Van Der Horst CM , Fiscus SA . AIDS 2015 29 (16) 2131-8 OBJECTIVE: The objective of this study is to assess nevirapine (NVP) resistance in infants who became infected in the three arms of the Breastfeeding, Antiretrovirals and Nutrition (BAN) study: daily infant NVP prophylaxis, triple maternal antiretrovirals or no extra intervention for 28 weeks of breastfeeding. DESIGN: A prospective cohort study. METHODS: The latest available plasma or dried blood spot specimen was tested from infants who became HIV-positive between 3 and 48 weeks of age. Population sequencing was used to detect mutations associated with reverse transcriptase inhibitor resistance. Sequences were obtained from 22 out of 25 transmissions in the infant-NVP arm, 23 out of 30 transmissions in the maternal-antiretroviral arm and 33 out of 38 transmissions in the control arm. RESULTS: HIV-infected infants in the infant-NVP arm were significantly more likely to have NVP resistance than infected infants in the other two arms of the trial, especially during breastfeeding through 28 weeks of age (56% in infant-NVP arm vs. 6% in maternal-antiretroviral arm and 11% in control arm, P = 0.004). There was a nonsignificant trend, suggesting that infants with NVP resistance tended to be infected earlier and exposed to NVP while infected for a greater duration than infants without resistance. CONCLUSION: Infants on NVP prophylaxis during breastfeeding are at a reduced risk of acquiring HIV, but are at an increased risk of NVP resistance if they do become infected. These findings point to the need for frequent HIV testing of infants while on NVP prophylaxis, and for the availability of antiretroviral regimens excluding NVP for treating infants who become infected while on such a prophylactic regimen. |
Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers
Chang TS , Wiener J , Dollard SC , Amin MM , Ellington S , Chasela C , Kayira D , Tegha G , Kamwendo D , Jamieson DJ , Van Der Horst C , Kourtis AP . AIDS 2015 29 (7) 831-836 BACKGROUND: Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown. METHODS: The Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi, randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms - mother (triple regimen), infant (nevirapine), or neither - for 28 weeks of breastfeeding, followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity, mortality, or postnatal HIV acquisition. RESULTS: At 24 weeks of age, CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%, and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05). CONCLUSION: Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding, pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV. |
Impact of daily cotrimoxazole on clinical malaria and asymptomatic parasitemias in HIV-exposed uninfected infants
Davis NL , Barnett EJ , Miller WC , Dow A , Chasela CS , Hudgens MG , Kayira D , Tegha G , Ellington SR , Kourtis AP , van der Horst C , Jamieson DJ , Juliano JJ . Clin Infect Dis 2015 61 (3) 368-74 BACKGROUND: Cotrimoxazole preventive therapy (CPT) is recommended for all HIV-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown. METHODS: We conducted an observational cohort study using data and dried blood spots (DBS) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence one year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV-negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBS at 12, 24 and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections. RESULTS: CPT was associated with a 70% (95% CI: 53-81%) relative reduction in the risk of asymptomatic infection between 6-36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics. CONCLUSIONS: CPT appears to reduce overall malaria infections with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits. |
Antiretroviral treatment is associated with iron deficiency in HIV-infected Malawian women that is mitigated with supplementation, but is not associated with infant iron deficiency during 24 weeks of exclusive breastfeeding
Widen EM , Bentley ME , Chasela CS , Kayira D , Flax VL , Kourtis AP , Ellington SR , Kacheche Z , Tegha G , Jamieson DJ , van der Horst CM , Allen LH , Shahab-Ferdows S , Adair LS . J Acquir Immune Defic Syndr 2015 69 (3) 319-28 OBJECTIVE: In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (via fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial conducted in Lilongwe, Malawi from 2004-2010. HIV-infected mothers (CD4>200 cells/ul) and their infants were randomly assigned to 28-week interventions: maternal-LNS/maternal-ARV (n=424), maternal-LNS/infant-ARV (n=426), maternal-LNS (n=334), maternal-ARV (n=425), infant-ARV (n=426), or control (n=334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n=537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR) and ferritin were tested with linear and Poisson regression. RESULTS: In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR>8.3 mg/L) (Risk ratio (RR): 3.1, p<0.01), but not in ARV-treated mothers receiving LNS (p=0.17). LNS without ARVs, was not associated with iron deficiency or anemia (p>0.1). In subsample infants, interventions were not associated with impaired iron status (all p-values>0.1). CONCLUSIONS: Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not appear to influence infant iron status; however, extended use needs to be evaluated. |
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. |
Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission
Davis NL , Miller WC , Hudgens MG , Chasela CS , Sichali D , Kayira D , Nelson JA , Stringer JS , Ellington SR , Kourtis AP , Jamieson DJ , van der Horst C . AIDS 2014 28 (18) 2739-2749 OBJECTIVE: Estimate association between postpartum antiretroviral adherence and breast milk HIV-1 transmission. DESIGN: Prospective cohort study. METHODS: Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study. Associations between postpartum antiretroviral adherence and rate of breast milk HIV-1 transmission were estimated using Cox models. We measured adherence over four postpartum time intervals using pill count, suspension bottle weight, and maternal self-report. Adherence was categorized and lagged by one interval. Missing adherence measures were multiply imputed. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. The primary endpoint was infant HIV-1 infection by 38 weeks of age among infants alive and uninfected at 5 weeks. RESULTS: Analyses included 1479 mother-infant pairs and 45 transmission events. Using pill count and bottle weight information, 22-40% of mother-infant pairs at any given interval were less than 90% adherent. Having at least 90% adherence was associated with a 52% [95% confidence interval (CI) 3-76] relative reduction in the rate of breast milk HIV-1 transmission, compared with having less than 90% adherence when controlling for study arm, breastfeeding status, and maternal characteristics. Complete case analysis rendered similar results (n = 501; relative reduction 59%, 95% CI 6-82). CONCLUSION: Nonadherence to extended postpartum antiretroviral regimens in 'real world' settings is likely to be higher than that seen in BAN. Identifying mothers with difficulty adhering to antiretrovirals, and developing effective adherence interventions, will help maximize benefits of antiretroviral provision throughout breastfeeding. |
Changes in soluble transferrin receptor and hemoglobin concentrations in Malawian mothers are associated with those values in their exclusively breastfed, HIV-exposed infants
Widen EM , Bentley ME , Kayira D , Chasela CS , Daza EJ , Kacheche ZK , Tegha G , Jamieson DJ , Kourtis AP , van der Horst CM , Allen LH , Shahab-Ferdows S , Adair LS . J Nutr 2014 144 (3) 367-73 Infant iron status at birth is influenced by maternal iron status during pregnancy; however, there are limited data on the extent to which maternal iron status is associated with infant iron status during exclusive breastfeeding. We evaluated how maternal and infant hemoglobin and iron status [soluble transferrin receptors (TfR) and ferritin] were related during exclusive breastfeeding in HIV-infected women and their infants. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial in Lilongwe, Malawi, in which HIV-infected women were assigned with a 2 x 3 factorial design to a lipid-based nutrient supplement (LNS), or no LNS, and maternal, infant, or no antiretroviral drug, and followed for 24 wk. Longitudinal models were used to relate postpartum maternal hemoglobin (n = 1926) to concurrently measured infant hemoglobin, adjusting for initial infant hemoglobin values. In a subsample, change in infant iron status (hemoglobin, log ferritin, log TfR) between 2 (n = 352) or 6 wk (n = 167) and 24 wk (n = 519) was regressed on corresponding change in the maternal indicator, adjusting for 2 or 6 wk values. A 1 g/L higher maternal hemoglobin at 12, 18, and 24 wk was associated with a 0.06 g/L (P = 0.01), 0.10 g/L (P < 0.001), and 0.06 g/L (P = 0.01), respectively, higher infant hemoglobin. In the subsample, a reduction in maternal log TfR and an increase in hemoglobin from initial measurement to 24 wk were associated with the same pattern in infant values (log TfR beta = -0.18 mg/L, P < 0.001; hemoglobin beta = 0.13 g/L, P = 0.01). Given the observed influence of maternal and initial infant values, optimizing maternal iron status in pregnancy and postpartum is important to protect infant iron status. This trial was registered at clinicaltrials.gov as NCT00164736. |
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. |
Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study
Flax VL , Bentley ME , Combs GF Jr , Chasela CS , Kayira D , Tegha G , Kamwendo D , Daza EJ , Fokar A , Kourtis AP , Jamieson DJ , van der Horst CM , Adair LS . Am J Clin Nutr 2014 99 (4) 950-6 BACKGROUND: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. OBJECTIVE: We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. DESIGN: HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. RESULTS: Overall, mean (+/-SD) maternal (range: 81.2 +/- 20.4 to 86.2 +/- 19.9 mug/L) and infant (55.6 +/- 16.3 to 61.0 +/- 15.4 mug/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 +/- 11.5 to 9.8 +/- 7.3 mug/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm. CONCLUSIONS: Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women. This trial was registered at clinicaltrials.gov as NCT00164736. |
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. |
Lipid-based nutrient supplements are feasible as a breastmilk replacement for HIV-exposed infants from 24 to 48 weeks of age
Flax VL , Bentley ME , Chasela CS , Kayira D , Hudgens MG , Kacheche KZ , Chavula C , Kourtis AP , Jamieson DJ , van der Horst CM , Adair LS . J Nutr 2013 143 (5) 701-7 The Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study randomized HIV-infected mothers and their infants to receive either maternal lipid-based nutrient supplements (LNS) during lactation or no LNS and then to 1 of 3 antiretroviral drug (ARV) arms (maternal, infant, or no drugs). Assigned interventions were provided from 0 to 28 wk and all infants (n = 1619) were given LNS during (24-28 wk) and following (28-48 wk) weaning. This paper assesses the feasibility of infant LNS as a breastmilk replacement and uses longitudinal random effects models to examine associations of interventions, morbidity, and season with weight-for-age (WAZ), length-for-age (LAZ), and BMI-for-age (BMIZ) Z-scores from 24 to 48 wk. Infant LNS adherence was high (94.1% ate it daily). From 24 to 48 wk, mean WAZ (-0.42 to -0.76 SD; P < 0.001) and LAZ (-0.93 to -1.56 SD; P < 0.001) steadily declined, whereas BMIZ remained >0 throughout. A higher LAZ was associated with assignment to the maternal LNS arm (beta=0.19; P < 0.05). Lower WAZ and BMIZ were associated with seasonal food insecurity (beta=-0.08 and -0.09, respectively; both P < 0.001), fever (beta=-0.07 and -0.13; both P < 0.001), diarrhea (beta=-0.19 and -0.23; both P < 0.001), and assignment to the infant ARV arm (beta=-0.17 and -0.17; both P < 0.05). The magnitude of the season and morbidity effects was small and BAN infants had higher weights and lengths than their counterparts in the general population. High LNS adherence and the modest impact of morbidity on growth indicate that LNS is a feasible breastmilk replacement for HIV-exposed infants weaned early, but controlled trials are needed to quantify the effects of LNS on growth in this population. |
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