Linda Barlow-Mosha

Makerere University - Johns Hopkins University Research Collaboration · Department of Paediatrics

Background Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. Methods ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of...

Background The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1104s study evaluated neuropsychological outcomes over 96 weeks in children living with HIV (CLHIV) aged 5–11 years at 6 Sub-Saharan African sites to explore associations between HIV-illness related biomarkers and neuropsychological outcomes.Methods C...

Background Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicen...

Sustainable birth defects surveillance systems provide countries with estimates of the prevalence of birth defects to guide prevention, care activities, and evaluate interventions. We used free and open-source software (Open Data Kit) to implement an electronic system to collect data for a hospital-based birth defects surveillance system at four ma...

Background Clinical trial investigators may need to evaluate treatment effects in a specific subgroup (or subgroups) of participants in addition to reporting results of the entire study population. Such subgroups lack power to detect a treatment effect, but there may be strong justification for borrowing information from a larger patient group with...

Background Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). Methods We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non–dolutegravir-based ART) in children...

Background The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited. Methods Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to esti...

Background: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. Methods: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in l...

Background: Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of "Test and Treat" WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uga...

Background Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals. Methods Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortio...

Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested ph...

Background: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and older mothers (age 20-34 years) in four urban hospitals. Methods: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous...

Background: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and mothers (age 20-34 years) in four urban hospitals. Methods: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous aborti...

Background: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and older mothers (age 20-34 years) in four urban hospitals. Methods: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous...

Background: Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of “Test and Treat” WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Ugan...

Background: Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of “Test and Treat” WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Ugan...

Background: Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). Methods: We e...

Background: In 2010, the World Health Assembly passed a resolution calling upon countries to prevent birth defects where possible. Though birth defects surveillance programs are an important source of information to guide implementation and evaluation of preventive interventions, many countries that shoulder the largest burden of birth defects do...

Depressive symptoms among HIV-positive (HIV+) women may negatively impact their health and possibly that of their young children through risk of compromised caregiving. We evaluated how depression symptoms in predominantly (97%) female caregivers relate to neurodevelopmental outcomes in their HIV affected children. Data come from the IMPAACT P1104s...

Purpose of Review The goal of this paper is to review the prevention of mother-to-child HIV transmission (PMTCT) research that informed World Health Organization (WHO) guidelines for PMTCT and describe the impact of worldwide scale-up of PMTCT programs and antiretroviral therapy (ART) coverage. The impact of these interventions on new pediatric inf...

Objective & design: Children with HIV infection (HIV+) are at neuropsychological risk, but few studies have evaluated this at multiple sites in low and middle income countries (LMICs). We compared neuropsychological outcomes at enrollment (>5 yrs age) among HIV+, HIV-uninfected perinatally-exposed (HEU), and HIV unexposed (HU) children from 4 sub-...

Background: Most clinical trials comparing treatments evaluate the separate effects on each of several efficacy and toxicity outcomes. However, population-averaged summary measures of treatment differences may not accurately reflect individual responses to treatment, and drawing conclusions about which treatment is "best" is straightforward if one...

Background The antiretroviral drug nevirapine and the antimalarial artemisinin-based combination therapy artemether-lumefantrine are commonly co-administered to treat malaria in the context of HIV. Nevirapine is a known inhibitor of cytochrome P450 3A4, which metabolizes artemether and lumefantrine. To address the concern that the antiretroviral ne...

PK parameters compared to the 3 control participants from P1079. (XLSX)

Characteristics of P1079 participants at study entry. (RTF)

Background: The 2016 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, recommended to start all HIV-infected children on antiretroviral therapy (ART). Here, we explore the possible benefits and risks of implementing universal ART for all HIV-infected children and ad...

Background: In 2012, Makerere University Johns - Hopkins University, and Mulago National Referral Hospital, with support from the National Institute of Health (under Grant number: NOT AI-01-023) undertook operational research at Mulago National Hospital PMTCT/PNC clinics. The study employed Peer Family Planning Champions to offer health education,...

Background: HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed. Methods: Thirty-one children from Malawi aged 4-62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We...

A and B: Kaplan Meier Curves depicting time to first (1st) positive blood smear (BS) and time to 1st confirmed clinical malaria (CCM) case. Overall, we observe a BS positive rate of 0.55 and 0.87 for the 1st year and the 1st two years of follow-up, respectively; for CCM rates are, 0.52 and 0.77 for the 1st year and the 1st two years, respectively....

Additional Statistical Analysis. (DOC)

Methods, Real Time PCR. (DOC)

Per Protocol Rates of BS and CCM (Negative Binomial Model, Data Censored at Switch from Regimen As Randomized). (DOC)

As-randomized in P1060 analyses (A. Cox Model and B. Negative Binomial). (DOC)

Background: IMPAACT-P1060 demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure (PrNVP). However, NVP-based ART had a marginal benefit in CD4% and growth. We compared five-year outcomes from this clinical trial. Methods: HIV-infected ART-eligible...

Background: Effective Prevention of Mother to child Transmission of HIV (PMTCT) relies heavily on follow-up of HIV-infected women and infants from antenatal, through postnatal, to the end of the breastfeeding period. In Uganda, postnatal (PNC) follow-up remains below 50 % creating a missed opportunity for linkage to comprehensive HIV care and earl...

This systematic review aimed to assess the safety and efficacy of antiretroviral options for postexposure prophylaxis (PEP). Recognizing the limited data on the safety and efficacy of antiretroviral drugs for PEP in children, this review was extended to include consideration of data on the use of antiretroviral drugs for treatment of infants and ch...

Background: In a randomized trial comparing nevirapine (NVP)-based versus lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) in HIV-infected children [primary endpoint discontinuation of study treatment for any reason or virologic failure by week 24] aged 2 months to 3 years, we assessed whether clinical, virologic, immunologic and saf...

We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 1...

The benefits of long-term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone...

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. Clinical, immunologic, and virologic outcomes of HIV-infecte...

Background: We used a novel high resolution melting (HRM) diversity assay to analyze HIV diversity in Ugandan children (age 0.6-12.4 years) who were enrolled in an observational study of antiretroviral treatment (ART). Children were maintained on ART if they were clinically and immunologically stable. Methods: HIV diversity was measured before A...

Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted...

Major obstacles remain in scaling up paediatric HIV treatment, including limited paediatric anti-retroviral drug options for resource-limited settings, challenges with adherence to liquid formulations and treatment fatigue with lifelong therapy. To determine levels of adherence to HAART in HIV-infected children at 12, 24, 36 and 48 weeks of follow-...

This article uses Scale of Change theory as a framework to guide global health researchers to synergistically target women's health outcomes in the context of improving their right to freedom, equity, and equality of opportunities. We hypothesize that health researchers can do so through six action strategies. These strategies include (1) becoming...

Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. A prospect...

We analyzed drug resistance in HIV-infected Ugandan children who received antiretroviral therapy in a prospective, observational study (2004-2006); some children had prior single-dose nevirapine (sdNVP) exposure. Children received stavudine (d4T), lamivudine (3TC), and nevirapine (NVP); treatment was continued if they were clinically and immunologi...

To compare the response to a nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in HIV-infected Ugandan children, exposed and nonexposed to single-dose NVP (sd NVP) at birth. HIV-infected study children were initiated on stavudine/lamivudine/NVP as a fixed dose combination. CD4 cell percent and HIV-1 RNA were documented at baseline...