Medicine and Health Sciences Commons^™

Immune Checkpoint Modulation Enhances Hiv-1 Antibody Induction., Todd Bradley, Masayuki Kuraoka, Chen-Hao Yeh, Ming Tian, Huan Chen, Derek W Cain, Xuejun Chen, Cheng Cheng, Ali H Ellebedy, Robert Parks, Maggie Barr, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Hilary Bouton-Verville, Sampa Santra, Kevin Wiehe, Mark G. Lewis, Ane Ogbe, Persephone Borrow, David Montefiori, Mattia Bonsignori, M Anthony Moody, Laurent Verkoczy, Kevin O. Saunders, Rafi Ahmed, John R. Mascola, Garnett Kelsoe, Frederick W. Alt, Barton F. Haynes

Manuscripts, Articles, Book Chapters and Other Papers

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env …

Evaluation Of The Hiv Infant Tracking System (Hitsystem) To Optimise Quality And Efficiency Of Early Infant Diagnosis: A Cluster-Randomised Trial In Kenya., Sarah Finocchario-Kessler, Brad Gautney, Anlin Cheng, Catherine Wexler, May Maloba, Niaman Nazir, Samoel Khamadi, Raphael Lwembe, Melinda Brown, Thomas A. Odeny, Jacinda K. Dariotis, Matthew Sandbulte, Natabhona Mabachi, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The HIV Infant Tracking System (HITSystem) is a web-based intervention linking providers of early infant diagnosis, laboratory technicians, and mothers and infants to improve outcomes for HIV-exposed infants. We aimed to evaluate the efficacy of the HITSystem on key outcomes of early infant diagnosis.

METHODS: We did a cluster-randomised trial at six hospitals in Kenya, which were matched on geographic region, resource level, and volume of patients (high, medium, and low). We randomly allocated hospitals within a matched pair to either the HITSystem (intervention; n=3) or standard of care (control; n=3). A random number generator was used to assign …

High Report Of Miscarriage Among Women Living With Hiv Who Want To Conceive In Uganda., Sarah Finocchario-Kessler, Kathy Goggin, Vincent S. Staggs, Rhoda K. Wanyenze, Jolly Beyeza-Kashesya, Deborah Mindry, Josephine Birungi, Glenn J Wagner

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Data on early miscarriage incidence is limited due to various social and methodological barriers. We report on 24-month pregnancy outcomes of 299 female Ugandan HIV clients in committed relationships with an intention to conceive. Miscarriage data are reported as auxiliary findings to a larger study (5R01HD072633).

RESULTS: 127 (42%) participants reported a pregnancy during the study; among the remaining 172, 82 indicated they stopped trying to conceive, and 16 dropped out prior to month 24. Of the 127 pregnancies, 55 (43%) resulted in live births, 67 (53%) in spontaneous miscarriage, 1 (< 1%) in stillbirth, 1 (< 1%) in abortion, and 3 (2%) in unknown outcomes. Three-quarters (75%) of miscarriages for which time until miscarriage was available were reported to occur in the first trimester (mean = 11.3 weeks gestation). The 67 participants who reported a miscarriage tended to be older (mean 33 vs. 30 years), but the significance of age did not persist after adjusting for multiple tests. We observed relatively low rates of pregnancy and high rates of miscarriage among this cohort of HIV-positive women wanting to conceive. Rigorously designed studies are needed to better understand the observed high rate of early miscarriage among HIV-infected women.

Study Protocol Of "Our Choice": A Randomized Controlled Trial Of The Integration Of Safer Conception Counseling To Transform Hiv Family Planning Services In Uganda., Kathy Goggin, Emily A. Hurley, Jolly Beyeza-Kashesya, Violet Gwokyalya, Sarah Finocchario-Kessler, Josephine Birungi, Deborah Mindry, Rhoda K Wanyenze, Glenn J Wagner

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: About 40% of HIV-positive women in sub-Saharan Africa become pregnant post-diagnosis. Despite about half of their pregnancies being planned, safer conception methods (SCM) are underutilized among serodiscordant couples, partially due to the fact that safer conception counseling (SCC) has not been integrated into routine HIV family planning (FP) services.

METHODS: Our Choice is a comprehensive FP intervention that promotes unbiased childbearing consultations to ensure clients receive SCC or contraception services to achieve their desired reproductive goals. The intervention is theoretically grounded and has demonstrated preliminarily feasibility and acceptance through pilot testing. This three-arm cluster randomized controlled trial compares two …

Utilization Of Prevention Of Mother-To-Child Transmission (Pmtct) Services Among Pregnant Women In Hiv Care In Uganda: A 24-Month Cohort Of Women From Pre-Conception To Post-Delivery., Rhoda K Wanyenze, Kathy Goggin, Sarah Finocchario-Kessler, Jolly Beyeza-Kashesya, Deborah Mindry, Josephine Birungi, Mahlet Woldetsadik, Glenn J Wagner

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: We assessed the uptake of prevention of mother-to-child transmission (PMTCT) services in a cohort of HIV infected women in care at The AIDS Support Organization Jinja and Kampala in Uganda, who were trying to conceive, over a period of 24 months, to inform the strengthening of PMTCT service access for women in care.

RESULTS: Of the 299 women 127 (42.5%) reported at least one pregnancy within 24 months; 61 women (48.0%) delivered a live child. Of the 55 who had a live birth at the first pregnancy, 54 (98.2%) used antenatal care (ANC) starting at 15.5 weeks of gestation …

Stigma Gets In My Way: Factors Affecting Client-Provider Communication Regarding Childbearing Among People Living With Hiv In Uganda., Jolly Beyeza-Kashesya, Rhoda K. Wanyenze, Kathy Goggin, Sarah Finocchario-Kessler, Mahlet Atakilt Woldetsadik, Deborah Mindry, Josephine Birungi, Glenn J. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Many HIV-affected couples living in sub-Saharan Africa desire to have children, but few quantitative studies have examined support for their childbearing needs. Our study explored client-provider communication about childbearing and safer conception among HIV clients in Uganda.

METHODS: 400 Ugandan HIV clients in committed relationships and with intentions to conceive were surveyed. Knowledge, attitudes and practices related to childbearing, and use of safer conception methods were assessed, including communication with providers about childbearing needs, the correlates of which were examined with bivariate statistics and logistic multivariate analysis.

RESULTS: 75% of the sample was female; 61% were on antiretroviral therapy; …

Evaluating Turnaround Times For Early Infant Diagnosis Samples In Kenya From 2011-2014: A Retrospective Analysis Of Hitsystem Program Data., Catherine Wexler, An-Lin Cheng, Brad Gautney, Sarah Finocchario-Kessler, Kathy Goggin, Samoel Khamadi, Hitsystem Team

Manuscripts, Articles, Book Chapters and Other Papers

Long turnaround times (TAT) for the processing and posting of results of infant HIV DNA PCR samples can hinder the success of early infant diagnosis (EID) programs. The HITSystem is an eHealth intervention that alerts staff when services are overdue or results are delayed. We conducted a retrospective analysis of 3669 HIV-exposed infants enrolled in 15 Kenya hospital EID programs and three laboratories using the HITSystem from 2011-2014. We assessed mean and median TAT from when a sample was: 1) obtained to when it was shipped to the laboratory, 2) shipped to when it was received at the laboratory, 3) …

Progress Toward Eliminating Mother To Child Transmission Of Hiv In Kenya: Review Of Treatment Guideline Uptake And Pediatric Transmission At Four Government Hospitals Between 2010 And 2012., Sarah Finocchario-Kessler, Kristine F. Clark, Samoel Khamadi, Brad J. Gautney, Vincent Okoth, Kathy Goggin, Hitsystem Study Team

Manuscripts, Articles, Book Chapters and Other Papers

We analyzed prevention of mother-to-child transmission (PMTCT) data from a retrospective cohort of n = 1365 HIV+ mothers who enrolled their HIV-exposed infants in early infant diagnosis services in four Kenyan government hospitals from 2010 to 2012. Less than 15 and 20 % of mother-infant pairs were provided with regimens that met WHO Option A and B/B+ guidelines, respectively. Annually, the gestational age at treatment initiation decreased, while uptake of Option B/B+ increased (all p's < 0.001). Pediatric HIV infection was halved (8.6-4.3 %), yet varied significantly by hospital. In multivariable analyses, HIV-exposed infants who received no PMTCT (AOR 4.6 [2.49, 8.62], p < 0.001), mixed foods (AOR 5.0 [2.77, 9.02], p < 0.001), and care at one of the four hospitals (AOR 3.0 [1.51, 5.92], p = 0.002) were more likely to be HIV-infected. While the administration and uptake of WHO PMTCT guidelines is improving, an expanded focus on retention and medication adherence will further reduce pediatric HIV transmission.

Predictors Of Infant Age At Enrollment In Early Infant Diagnosis Services In Kenya., Kathy Goggin, Catherine Wexler, Niaman Nazir, Vincent S. Staggs, Brad Gautney, Vincent Okoth, Samoel A Khamadi, Andrea Ruff, Michael Sweat, An-Lin Cheng, Sarah Finocchario-Kessler

Manuscripts, Articles, Book Chapters and Other Papers

Despite the importance of early detection to signal lifesaving treatment initiation for HIV+ infants, early infant diagnosis (EID) services have received considerably less attention than other aspects of prevention of mother to child transmission care. This study draws on baseline data from an on-going cluster randomized study of an intervention to improve EID services at six government hospitals across Kenya. Two logistic regressions examined potential predictors of "on time" (infant ≤6 weeks of age) vs. "late" (≥7 weeks) and "on time" versus "very late" (≥12 weeks) EID engagement among 756 mother-infant pairs. A quarter of the infants failed to get …

Toward Earlier Inclusion Of Pregnant And Postpartum Women In Tuberculosis Drug Trials: Consensus Statements From An International Expert Panel., Amita Gupta, Jyoti S. Mathad, Susan M. Abdel-Rahman, Jessica D. Albano, Radu Botgros, Vikki Brown, Renee S. Browning, Liza Dawson, Kelly E. Dooley, Devasena Gnanashanmugam, Beatriz Grinsztejn, Sonia Hernandez-Diaz, Patrick Jean-Philippe, Peter Kim, Anne D. Lyerly, Mark Mirochnick, Lynne M. Mofenson, Grace Montepiedra, Jeanna Piper, Leyla Sahin, Radojka Savic, Betsy Smith, Hans Spiegel, Soumya Swaminathan, D Heather Watts, Amina White

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human …

Multi-Level Correlates Of Safer Conception Methods Awareness And Attitudes Among Ugandan Hiv Clients With Fertility Intentions., Glenn J. Wagner, Mahlet A. Woldetsadik, Jolly Beyeza-Kashesya, Kathy Goggin, Deborah Mindry, Sarah Finocchario-Kessler, Sarah Khanakwa, Rhoda K. Wanyenze

Manuscripts, Articles, Book Chapters and Other Papers

Many people living with HIV desire childbearing, but low cost safer conception methods (SCM) such as timed unprotected intercourse (TUI) and manual self-insemination (MSI) are rarely used. We examined awareness and attitudes towards SCM, and the correlates of these constructs among 400 HIV clients with fertility intentions in Uganda. Measures included awareness, self-efficacy, and motivation regarding SCM, as well as demographics, health management, partner and provider characteristics. Just over half knew that MSI (53%) and TUI (51%) reduced transmission risk during conception, and 15% knew of sperm washing and pre-exposure prophylaxis. In separate regression models for SCM awareness, motivation, and …

Consumption Of Sutherlandia Frutescens By Hiv-Seropositive South African Adults: An Adaptive Double-Blind Randomized Placebo Controlled Trial., Douglas Wilson, Kathy Goggin, Karen Williams, Mary M. Gerkovich, Nceba Gqaleni, James Syce, Patricia Bartman, Quinton Johnson, William R. Folk

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sutherlandia frutescens (L.) R. Br. is widely used as an over the counter complementary medicine and in traditional medications by HIV seropositive adults living in South Africa; however the plant's safety has not been objectively studied. An adaptive two-stage randomized double-blind placebo controlled study was used to evaluate the safety of consuming dried S. frutescens by HIV seropositive adults with CD4 T-lymphocyte count of >350 cells/μL.

METHODS: In Stage 1 56 participants were randomized to S. frutescens 400, 800 or 1,200 mg twice daily or matching placebo for 24 weeks. In Stage 2 77 additional participants were randomized to …

Improving Early Infant Hiv Diagnosis In Kenya: Study Protocol Of A Cluster-Randomized Efficacy Trial Of The Hitsystem., Sarah Finocchario-Kessler, Kathy Goggin, Samoel Khamadi, Brad Gautney, Jacinda K. Dariotis, Charles Bawcom, An-Lin Cheng, Niaman Nazir, Catherine Martin, Andrea Ruff, Michael Sweat, Vincent Okoth

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Early infant diagnosis among human immunodeficiency virus (HIV)-exposed infants is a critical component of prevention of mother-to-child transmission programs. Barriers to early infant diagnosis include poor uptake, low retention at designated re-testing intervals, delayed test results, passive systems of communication, and poor linkage to treatment. This study will evaluate the HIV Infant Tracking System (HITSystem), an eHealth intervention that streamlines communication and accountability between the key early infant diagnosis stakeholders: HIV+ mothers and their HIV-exposed infants, healthcare providers, and central laboratory personnel. It is hypothesized that the HITSystem will significantly improve early infant diagnosis retention at 9 and 18 …

Strong Relationship Between Oral Dose And Tenofovir Hair Levels In A Randomized Trial: Hair As A Potential Adherence Measure For Pre-Exposure Prophylaxis (Prep)., Albert Y. Liu, Qiyun Yang, Yong Huang, Peter Bacchetti, Peter L. Anderson, Chengshi Jin, Kathy Goggin, Kristefer Stojanovski, Robert Grant, Susan P. Buchbinder, Ruth M. Greenblatt, Monica Gandhi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults.

METHODS: A …