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BACKGROUND: Few studies have examined the influence of pregnancy and hormonal contraception on HIV-related deaths in African women. Rwanda is a country with high fertility, high HIV prevalence, and frequent use of hormonal contraception in urban areas. METHODS: Data from a prospective cohort study of 460 HIV-infected urban childbearing (18-35 years) women followed at 6-monthly intervals for 6 years in Kigali, Rwanda, were analyzed. The relationship of time-dependent measures of pregnancy and hormonal contraceptive use to death from HIV disease was assessed with multivariate models. RESULTS: Incident pregnancy was not associated with elevated risk of death among HIV-infected women. Oral and injectable hormonal contraceptive use had borderline protective effects associated with reduced mortality (HR 0.40, 95% CI 0.15-1.07 and HR 0.48, 95% CI 0.21-1.08 for mortality, respectively) in a multivariate model including time-dependent measures. CONCLUSIONS: The results point to the benefits of integrating family planning and HIV services. In a highly pronatalist society, such as Rwanda, which is experiencing high HIV prevalence, service integration affords an opportunity to provide HIV testing to women at risk of pregnancy and to promote family planning among HIV-positive women. [ABSTRACT FROM AUTHOR]

Background: Most individuals show immunity to SARS-CoV-2 from vaccination or infection, or both. We aimed to determine the safety and immunogenicity of an omicron-containing COVID-19 vaccine (mRNA-1273.222) in vaccine-naive adolescents who were SARS-CoV-2 positive., Methods: Part 3 of the phase 2/3 TeenCOVE trial was a phase 3, open-label, single-arm part done in the USA and the Dominican Republic that enrolled healthy, vaccine-naive adolescents (aged 12-17 years) to receive two 50 μg doses of mRNA-1273.222 (ancestral strain Wuhan-Hu-1 and omicron subvariants BA.4 and BA.5), 6 months apart. Primary reactogenicity and safety outcomes included assessment of solicited local or systemic adverse reactions 7 days after vaccination, and unsolicited and prespecified adverse events throughout study participation. Inferred effectiveness (primary immunogenicity outcome) was established by comparing neutralising antibody responses 28 days after dose 1 of mRNA-1273.222 in SARS-CoV-2-positive adolescents with responses 28 days after dose 2 of mRNA-1273 100 μg primary series in SARS-CoV-2-negative young adults (aged 18-25 years) from the COVE trial. This study is registered with ClinicalTrials.gov (NCT04649151)., Findings: Between Dec 21, 2022, and June 5, 2023, 379 adolescents (378 of whom were SARS-CoV-2 positive) received at least one mRNA-1273.222 dose and were included in the safety analysis set. The reactogenicity profile was favourable compared with the mRNA-1273 primary series, with no new safety concerns identified. Unsolicited adverse events were reported in 49 (13%) of 379 participants; no deaths or adverse events leading to study discontinuation were reported. The immunogenicity set included 245 adolescents from the per-protocol immunogenicity subset who were SARS-CoV-2 positive at baseline and 296 young adults who were SARS-CoV-2 negative. Compared with the mRNA-1273 primary series in SARS-CoV-2-negative young adults, a single dose of mRNA-1273.222 induced superior (geometric mean ratio [GMR] 95% CI lower bound >1) neutralising antibody responses against omicron BA.4 and BA.5 (GMR 48·95 [95% CI 44·21-54·21]) and non-inferior (GMR 95% CI lower bound >0·667) neutralising antibody responses against ancestral SARS-CoV-2 (GMR 4·25 [95% CI 3·69-4·88]) in SARS-CoV-2-positive adolescents., Interpretation: In vaccine-naive, SARS-CoV-2-positive adolescents, single-dose mRNA-1273.222 was effective against COVID-19 based on successful immunobridging to the two-dose mRNA-1273 primary series in young adults. The findings support a simplified single-dose vaccination schedule with variant-containing mRNA vaccines, regardless of previous vaccination status., Funding: Moderna., Competing Interests: Declaration of interests ALF, WD, WX, YS, GC, MO, BG, JMM, RD, and FP are employees of Moderna, and hold stock or stock options in the company. FP served on the scientific advisory board of CEPI from June, 2021, to June, 2023. AY is a consultant for Moderna. DT, CR-A, and PM declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Solid organ transplant recipients (SOTRs) are at high risk for severe COVID-19., Methods: This open-label, phase 3b trial evaluated mRNA-1273 in 137 kidney and 77 liver SOTRs and 20 immunocompetent participants. In part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received 2 doses. In part B, an additional 100-µg dose was offered ≥4 months after the primary series. Here, we report interim trial results., Results: mRNA-1273 was well-tolerated in SOTRs. Four serious adverse events were considered vaccine related by the investigator in 3 SOTRs with preexisting comorbidities. No vaccine-related biopsy-proven organ rejection events or deaths were reported. mRNA-1273 elicited modest neutralizing antibody responses after dose 2 and improved responses after dose 3 in SOTRs. Post-dose 3 responses among liver SOTRs were comparable to post-dose 2 responses in immunocompetent participants. Post-additional dose responses were increased in SOTRs, regardless of primary series vaccination. In liver SOTRs, post-additional dose responses were ∼3-fold higher versus post-dose 2 but lower than immunocompetent participant responses. Most kidney SOTRs received multiple immunosuppressants and had reduced antibody responses versus liver SOTRs., Conclusions: mRNA-1273 was well-tolerated, and dose 3 and the additional dose improved antibody responses among SOTRs., Clinical Trials Registration: NCT04860297., Competing Interests: Potential conflicts of interest. A. L. F., F. P., D. S., U. S., I. L. L., E. d. W., B. G., H. Z., J. M. M., and R. D. are employees of Moderna, Inc., and may hold stock/stock options in the company. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites. The open-label (Parts B and C) primary objectives were evaluation of long-term safety and effectiveness of primary vaccination plus a 50-µg booster dose; immunogenicity was a secondary objective. Of 29,035 open-label participants, 19,609 received boosters (mRNA-1273 [n = 9647]; placebo-mRNA-1273 [n = 9952]; placebo [n = 10] groups). Booster safety was consistent with that reported for primary vaccination. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with a significant, 47.0% (95% CI : 39.0-53.9%) reduction of Omicron BA.1 incidence (24.6 [23.4 - 25.8] vs 46.4 [40.6 - 52.7]/1000 person-months). In an exploratory Cox regression model adjusted for time-varying covariates, a longer median interval between primary vaccination and boosting (mRNA-1273 [13 months] vs placebo-mRNA-1273 [8 months]) was associated with significantly lower, COVID-19 risk (24.0% [16.0% - 32.0%]) during Omicron BA.1 predominance. Boosting elicited greater immune responses against SARS-CoV-2 than primary vaccination, irrespective of prior SARS-CoV-2 infection. Primary vaccination and boosting with mRNA-1273 demonstrated acceptable safety, effectiveness and immunogenicity against COVID-19, including emergent variants., (© 2024. The Author(s).)

Background: Longitudinal changes in vaccination-induced immune response remain inadequately characterized in adolescents. We present long-term safety, immunogenicity, and COVID-19 incidence following a 2-dose mRNA-1273 100-μg primary series, and immunogenicity following a single dose of mRNA-1273 50 μg in vaccine-naïve adolescents., Methods: TeenCOVE (NCT04649151) Part 1 randomized adolescents (12-17 years) to 2-dose mRNA-1273 100 μg (n = 2490) or placebo (n = 1243) 28 days apart. Subsequently, placebo recipients (n = 91) could receive open-label mRNA-1273. Primary objectives included prespecified adverse events through 12 months; secondary objectives were COVID-19 incidence and neutralizing and spike-binding antibodies (nAbs/bAbs) against SARS-CoV-2 (ancestral/variants) through 12 months (study period: December 2020-January 2022). In Part 2, vaccine-naïve adolescents (n = 52) received up to 2 doses of mRNA-1273 50 μg; interim analysis included Day 28 (D28) nAbs post-injection 1 in SARS-CoV-2-baseline-positive participants (serologic/virologic evidence of prior infection)., Findings: In SARS-CoV-2-baseline-negative adolescents (N = 369), mRNA-1273 induced robust nAb responses versus baseline (geometric mean concentration [GMC] = 11; 95% CI, 11-12) at D28 (1868 [1759-1985]), 6 months (625 [583-670]) and 12 months (550 [490-618]) post-injection 2. Similar bAb responses were observed to alpha/beta/delta/gamma variants; nAb/bAb responses were similar in SARS-CoV-2-baseline-positive adolescents. The 2-dose mRNA-1273 100-μg primary series was generally well-tolerated; one case of nonserious, moderate, probable acute myocarditis resolved by 8 days from symptom onset. A single dose of mRNA-1273 50 μg in SARS-CoV-2-baseline-positive adolescents induced higher D28 nAb GMCs against ancestral SARS-CoV-2 than 2-dose mRNA-1273 100 μg in young adults (geometric mean ratio = 4.322 [3.274-5.707])., Interpretation: The overall risk-benefit profile of mRNA-1273 remains favorable in adolescents, with durable 12-month immune responses against SARS-CoV-2 (ancestral/variants). A single mRNA-1273 50-μg injection in vaccine-naïve adolescents elicited robust immune responses against SARS-CoV-2., Funding: This project has been funded in whole or in part with federal funds by the Department of Health and Human Services, United States; Administration for Strategic Preparedness and Response, United States; Biomedical Advanced Research and Development Authority, United States, under Contract No. 75A50120C00034. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Department of Health and Human Services or its components., Competing Interests: A Figueroa, H Zhou, W Deng, W Xu, S Lussier, B Girard, F Dutko, F Priddy, J Miller, and R Das are employees of and shareholders in Moderna, Inc. K Ali has nothing to disclose. G Berman received vaccine clinical research payments for work completed for Moderna, Inc. A Yeakey and K Slobod are consultants and were contracted by Moderna Inc. for this study., (© 2024 The Author(s).)

Background: Variant-containing mRNA vaccines for COVID-19 to broaden protection against SARS-CoV-2 variants are recommended based on findings in adults. We report interim safety and immunogenicity of an omicron BA.1 variant-containing (mRNA-1273.214) primary vaccination series and booster dose in paediatric populations., Methods: This open-label, two-part, non-randomised phase 3 trial enrolled participants aged 6 months to 5 years at 24 US study sites. Eligible participants were generally healthy or had stable chronic conditions, without known SARS-CoV-2 infection in the previous 90 days. Individuals who were acutely ill or febrile 1 day before or at the screening visit or those who previously received other COVID-19 vaccines (except mRNA-1273 for part 2) were excluded. In part 1, SARS-CoV-2-vaccine-naive participants received two-dose mRNA-1273.214 (25 μg; omicron BA.1 and ancestral Wuhan-Hu-1 mRNA) primary series. In part 2, participants who previously completed the two-dose mRNA-1273 (25 μg) primary series in KidCOVE (NCT04796896) received a mRNA-1273.214 (10 μg) booster dose. Primary study outcomes were safety and reactogenicity of the mRNA-1273.214 primary series (part 1) or booster dose (part 2) as well as the inferred effectiveness of mRNA-1273.214 based on immune responses against ancestral SARS-CoV-2 (D614G) and omicron BA.1 variant at 28 days post-primary series (part 1) or post-booster dose (part 2). The safety set included participants who received at least one dose of the study vaccine; the immunogenicity set included those who provided immunogenicity samples. Interim safety and immunogenicity are summarised in this analysis as of the data cutoff date (Dec 5, 2022). This trial is registered with ClinicalTrials.gov, NCT05436834., Findings: Between June 21, 2022, and Dec 5, 2022, 179 participants received one or more doses of mRNA-1273.214 primary series (part 1) and 539 received a mRNA-1273.214 booster dose (part 2). The safety profile within 28 days after either dose of the mRNA-1273.214 primary series and the booster dose was consistent with that of the mRNA-1273 primary series in this age group, with no new safety concerns or vaccine-related serious adverse events observed. At 28 days after primary series dose 2 and the booster dose, both mRNA-1273.214 primary series (day 57, including all participants with or without evidence of prior SARS-CoV-2 infection at baseline) and booster (day 29, including participants without evidence of prior SARS-CoV-2 infection at baseline) elicited responses that were superior against omicron-BA.1 (geometric mean ratio part 1: 25·4 [95% CI 20·1-32·1] and part 2: 12·5 [11·0-14·3]) and non-inferior against D614G (part 1: 0·8 [0·7-1·0] and part 2: 3·1 [2·8-3·5]), compared with neutralising antibody responses induced by the mRNA-1273 primary series (in a historical comparator group)., Interpretation: mRNA-1273.214 was immunogenic against BA.1 and D614G in children aged 6 months to 5 years, with a comparable safety profile to mRNA-1273, when given as a two-dose primary series or a booster dose. These results are aligned with the US Centers for Disease Control and Prevention recommendations for the use of variant-containing vaccines for continued protection against the emerging variants of SARS-CoV-2., Funding: Moderna., Competing Interests: Declaration of interests AD, RP, KH, BG, WZ, WD, HZ, SSG, JMM, FP, and RD are employees of Moderna, and hold stock or stock options in the company. AY, KS, and BJK are consultants for Moderna. BJK is a member of the Children's Hospital of Philadelphia Vaccine Education Center research team and no payments have been received for this study. RB, KA, MT, CG, and RAC declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The mRNA-1345 vaccine demonstrated efficacy against RSV disease with acceptable safety in adults ≥60 years in the ConquerRSV trial. Here, humoral immunogenicity results from the trial are presented., Methods: This phase 2/3 trial randomly assigned adults (≥60 years) to mRNA-1345 50-µg encoding prefusion F (preF) glycoprotein (n = 17,793) vaccine or placebo (n = 17,748). RSV-A and RSV-B neutralizing antibody (nAb) and preF binding antibody (bAb) levels at baseline and day 29 post-vaccination were assessed in a per-protocol immunogenicity subset ([PPIS]; mRNA-1345, n = 1515; placebo, n = 333)., Results: Day 29 nAb geometric mean titers (GMTs) increased 8.4-fold against RSV-A and 5.1-fold against RSV-B from baseline. Seroresponses (4-fold rise from baseline) in the mRNA-1345 groups were 74.2% and 56.5% for RSV-A and RSV-B, respectively. Baseline GMTs were lower among participants who met the seroresponse criteria than those who did not. mRNA-1345 induced preF bAbs at day 29, with a pattern similar to nAbs. Day 29 antibody responses across demographic and risk subgroups were generally consistent with the overall PPIS., Conclusion: mRNA-1345 enhanced RSV-A and RSV-B nAbs and preF bAbs in adults (≥60 years) across various subgroups, including those at risk for severe disease, consistent with its demonstrated efficacy in the prevention of RSV disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Vaccination against SARS-CoV-2 is an integral pillar of the public health approach to COVID-19. With the emergence of variants of concern that increase transmissibility and escape from vaccine- or infection-induced protection, vaccines have been developed to more closely match the newly circulating SARS-CoV-2 strains to improve protection. The safety and immunogenicity of multiple authorized messenger RNA (mRNA)-based COVID-19 vaccines targeting the omicron sublineage (BA.1, BA.4/BA.5, and XBB.1.5) have been demonstrated in several clinical trials among adults and children., Areas Covered: This review will comprehensively detail the available evidence (published through July 2024) from ongoing clinical trials on omicron variant-containing mRNA-1273 vaccines administered as additional doses in previously vaccinated target demographics., Expert Opinion: Across three clinical trials, omicron variant-containing mRNA-1273 vaccines induced immune responses to vaccine-matched omicron strains as well as ancestral SARS-CoV-2, with a safety and reactogenicity profile comparable to the original mRNA-1273 vaccine. Combined with pivotal data demonstrating the safety, efficacy, and effectiveness of the original mRNA-1273 vaccine, these findings support the use of variant-containing mRNA-1273 vaccines and provide confidence that expeditious development of updated vaccines using this established mRNA platform can maintain protection against COVID-19.

Background: From 2019 to 2021, Rwandan residents of the border with the Democratic Republic of the Congo were offered the Ad26.ZEBOV (adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein) and MVA-BN-Filo (modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and nucleoprotein from Tai Forest viruses) Ebola vaccine regimen., Methods: Nonpregnant persons aged ≥2 years were eligible. Unsolicited adverse events (UAEs) were reported through phone calls or visits, and serious adverse events (SAEs) were recorded per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines., Results: Following Ad26.ZEBOV, UAEs were reported by 0.68% of 216 113 vaccinees and were more common in younger children (aged 2-8 years, 1.2%) compared with older children (aged 9-17 years, 0.4%) and adults (aged ≥18 years, 0.7%). Fever and headache were the most reported symptoms. All 17 SAEs related to vaccine were in children aged 2-8 years (10 postvaccination febrile convulsions ± gastroenteritis and 7 fever and/or gastroenteritis). The incidence of febrile seizures was 8 of 26 062 (0.031%) prior to initiation of routine acetaminophen in December 2020 and 2 of 15 897 (0.013%) thereafter. Nonobstetric SAEs were similar in males and females. All 20 deaths were unrelated to vaccination. Young girls and adult women with UAEs were less likely to receive the second dose than those without UAEs. Seven unrelated SAEs occurred in 203 267 MVA-BN-Filo recipients., Conclusions: Postvaccination febrile convulsions in young children were rare but not previously described after Ad26.ZEBOV and were reduced with routine acetaminophen. The regimen was otherwise safe and well-tolerated., Competing Interests: Potential conflicts of interest. J. No. is an employee of J&J Global Public Health R&D, engaged by Janssen Vaccines & Prevention, the manufacturer of the 2-dose Ebola vaccine regimen utilized in the UMURINZI campaign. N. H. and M. K. are employees of Janssen Vaccines & Prevention, the manufacturer of the 2-dose Ebola vaccine regimen utilized in the UMURINZI campaign. C. R. is currently a retired employee of Janssen Vaccines & Prevention but served as the medical leader during the conduct of this campaign. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Measles is a vaccine-preventable viral disease whose vaccination coverage remains low in Zambia, where the target group for vaccination is children aged 9 to 18 months. In addition to inadequate measles vaccination coverage among children, few studies address potential resultant immunity gaps among adults. We analyzed data from a simulated HIV vaccine efficacy trial (SiVET) conducted from 2015-2017 among adult Zambian women of childbearing age to determine measles antibody seroprevalence before and after vaccination with the measles, mumps and rubella (MMR) vaccine. We used MMR vaccine as a substitute for an experimental HIV vaccine as part of a simulation exercise to prepare for an HIV vaccine efficacy trial. We found that 75% of women had measles antibodies prior to receiving MMR, which increased to 98% after vaccination. In contrast, mumps and rubella antibody prevalence was high before (93% and 97%, respectively) and after (99% and 100%, respectively) vaccination. The low baseline measles seropositivity suggests an immunity gap among women of childbearing age. We recommend that measles vaccination programs target women of childbearing age, who can pass antibodies on to neonates. Moreover, administering the MMR vaccine to clinical trial candidates could prevent measles, mumps or rubella-related adverse events during actual trials.

Background: Risks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of the 2-dose Ebola vaccine regimen in healthy adult pregnant women. This 2-dose regimen has been shown to be safe, judged effective, and approved in non-pregnant populations., Methods: A total of 2000 adult (≥ 18 years of age) pregnant women will be enrolled from antenatal care facilities in Western Rwanda and randomized (1:1) to receive the 2-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo (group A)) or control (unvaccinated pregnant women (group B)). The primary objectives are to (1) assess adverse maternal/fetal outcomes in randomized pregnant women up to 1.5 months after delivery and (2) assess adverse neonatal/infant outcomes in neonates/infants born to randomized women up to 3.5 months after birth. The frequency and relatedness of all serious adverse events in women and newborns from randomization or birth, respectively, until study end will be reported. The reactogenicity and unsolicited adverse events of the 2-dose Ebola vaccine regimen in all vaccinated pregnant women (group A) will be reported. We will also assess the immunogenicity of the 2-dose Ebola vaccine regimen in 150 pregnant women who are anticipated to receive both vaccine doses within the course of their pregnancy (a subset of the 1000 pregnant vaccinated women from group A) compared to 150 non-pregnant women vaccinated after delivery (a subset of group B). The persistence of maternal antibodies in 75 infants born to women from the group A subset will be assessed. Exploratory analyses include assessment of acceptability of the 2-dose Ebola vaccine regimen among group A and assessment of maternal antibodies in breast milk in 50 women from group A and 10 controls (women from group B prior to vaccination)., Discussion: This study is intended to support a label variation to relax restrictions on use in pregnant women, a vulnerable population with high medical need., Trial Registration: Clinicaltrials.gov NCT04556526 . September 21, 2020., (© 2022. The Author(s).)

Introduction: Intramuscular electroporation (IM/EP) is a vaccine delivery technique that improves the immunogenicity of DNA vaccines. We evaluated the acceptability and tolerability of electroporation among healthy African study participants., Methods: Forty-five participants were administered a DNA vaccine (HIV-MAG) or placebo by electroporation at three visits occurring at four week-intervals. At the end of each visit, participants were asked to rate pain at four times: (1) when the device was placed on the skin and vaccine injected, before the electrical stimulation, (2) at the time of electrical stimulation and muscle contraction, and (3) at 10 minutes and (4) 30 minutes after the procedure was completed. For analyses, pain level was dichotomized as either "acceptable" (none/slight/uncomfortable) or "too much" (Intense, severe, and very severe) and examined over time using repeated measures models. Optional brief comments made by participants were summarized anecdotally., Results: All 45 participants completed all three vaccination visits; none withdrew from the study due to the electroporation procedure. Most (76%) reported pain levels as acceptable at every time point across all vaccination visits. The majority of "unacceptable" pain was reported at the time of electrical stimulation. The majority of the participants (97%) commented that they preferred electroporation to standard injection., Conclusion: Repeated intramuscular electroporation for vaccine delivery was found to be acceptable and feasible among healthy African HIV vaccine trial participants. The majority of participants reported an acceptable pain level at all vaccination time points. Further investigation may be warranted into the value of EP to improve immunization outcomes. ClinicalTrials.gov NCT01496989., Competing Interests: PEF, MP and FP were employees of IAVI at the time of the study. DH is an employee of Ichor Medical Sciences Inc which owns the rights to the TriGrid Delivery System. The rest of the authors have no competing interests.

Few human immunodeficiency virus (HIV)-infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, "viral control") in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51-2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3-9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3-3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1-2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0-3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: More than 1·8 million new cases of HIV-1 infection were diagnosed worldwide in 2016. No licensed prophylactic HIV-1 vaccine exists. A major limitation to date has been the lack of direct comparability between clinical trials and preclinical studies. We aimed to evaluate mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in parallel studies in humans and rhesus monkeys to define the optimal vaccine regimen to advance into clinical efficacy trials., Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled phase 1/2a trial (APPROACH). Participants were recruited from 12 clinics in east Africa, South Africa, Thailand, and the USA. We included healthy, HIV-1-uninfected participants (aged 18-50 years) who were considered at low risk for HIV-1 infection. We randomly assigned participants to one of eight study groups, stratified by region. Participants and investigators were blinded to the treatment allocation throughout the study. We primed participants at weeks 0 and 12 with Ad26.Mos.HIV (5 × 10 10 viral particles per 0·5 mL) expressing mosaic HIV-1 envelope (Env)/Gag/Pol antigens and gave boosters at weeks 24 and 48 with Ad26.Mos.HIV or modified vaccinia Ankara (MVA; 10 8 plaque-forming units per 0·5 mL) vectors with or without high-dose (250 μg) or low-dose (50 μg) aluminium adjuvanted clade C Env gp140 protein. Those in the control group received 0·9% saline. All study interventions were administered intramuscularly. Primary endpoints were safety and tolerability of the vaccine regimens and Env-specific binding antibody responses at week 28. Safety and immunogenicity were also assessed at week 52. All participants who received at least one vaccine dose or placebo were included in the safety analysis; immunogenicity was analysed using the per-protocol population. We also did a parallel study in rhesus monkeys (NHP 13-19) to assess the immunogenicity and protective efficacy of these vaccine regimens against a series of six repetitive, heterologous, intrarectal challenges with a rhesus peripheral blood mononuclear cell-derived challenge stock of simian-human immunodeficiency virus (SHIV-SF162P3). The APPROACH trial is registered with ClinicalTrials.gov, number NCT02315703., Findings: Between Feb 24, 2015, and Oct 16, 2015, we randomly assigned 393 participants to receive at least one dose of study vaccine or placebo in the APPROACH trial. All vaccine regimens demonstrated favourable safety and tolerability. The most commonly reported solicited local adverse event was mild-to-moderate pain at the injection site (varying from 69% to 88% between the different active groups vs 49% in the placebo group). Five (1%) of 393 participants reported at least one grade 3 adverse event considered related to the vaccines: abdominal pain and diarrhoea (in the same participant), increased aspartate aminotransferase, postural dizziness, back pain, and malaise. The mosaic Ad26/Ad26 plus high-dose gp140 boost vaccine was the most immunogenic in humans; it elicited Env-specific binding antibody responses (100%) and antibody-dependent cellular phagocytosis responses (80%) at week 52, and T-cell responses at week 50 (83%). We also randomly assigned 72 rhesus monkeys to receive one of five different vaccine regimens or placebo in the NHP 13-19 study. Ad26/Ad26 plus gp140 boost induced similar magnitude, durability, and phenotype of immune responses in rhesus monkeys as compared with humans and afforded 67% protection against acquisition of SHIV-SF162P3 infection (two-sided Fisher's exact test p=0·007). Env-specific ELISA and enzyme-linked immunospot assay responses were the principal immune correlates of protection against SHIV challenge in monkeys., Interpretation: The mosaic Ad26/Ad26 plus gp140 HIV-1 vaccine induced comparable and robust immune responses in humans and rhesus monkeys, and it provided significant protection against repetitive heterologous SHIV challenges in rhesus monkeys. This vaccine concept is currently being evaluated in a phase 2b clinical efficacy study in sub-Saharan Africa (NCT03060629)., Funding: Janssen Vaccines & Prevention BV, National Institutes of Health, Ragon Institute of MGH, MIT and Harvard, Henry M Jackson Foundation for the Advancement of Military Medicine, US Department of Defense, and International AIDS Vaccine Initiative., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Measuring PrEP adherence remains challenging. In 2009-2010, the International AIDS Vaccine Initiative randomized phase II trial participants to daily tenofovir disoproxil fumarate/emtricitabine or placebo in Uganda and Kenya. Adherence was measured by electronic monitoring (EM), self-report (SR), and drug concentrations in plasma and hair. Each adherence measure was categorised as low, moderate, or high and also considered continuously; the incremental value of combining measures was determined. Forty-five participants were followed over 4 months. Discrimination for EM adherence by area under receiver operating curves (AROC) was poor for SR (0.53) and best for hair (AROC 0.85). When combining hair with plasma or hair with self-report, discrimination was improved (AROC > 0.9). Self-reported adherence was of low utility by itself. Hair level was the single best PK measure to predict EM-assessed adherence; the other measurements had lower discrimination values. Combining short-term (plasma) and long-term (hair) metrics could be useful to assess patterns of drug-taking in the context of PrEP.

Background: Digital technologies, especially if used in novel ways, provide a number of potential advantages to clinical research in trials related to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) and may greatly facilitate operations as well as data collection and analysis. These technologies may even allow answering questions that are not answerable with older technologies. However, they come with a variety of potential concerns for both the participants and the trial sponsors. The exact challenges and means for alleviation depend on the technology and on the population in which it is deployed, and the rapidly changing landscape of digital technologies presents a challenge for creating future-proof guidelines for technology application., Objective: The aim of this study was to identify and summarize some common themes that are frequently encountered by researchers in this context and highlight those that should be carefully considered before making a decision to include these technologies in their research., Methods: In April 2016, the Global HIV Vaccine Enterprise surveyed the field for research groups with recent experience in novel applications of digital technologies in HIV clinical research and convened these groups for a 1-day meeting. Real-world uses of various technologies were presented and discussed by 46 attendees, most of whom were researchers involved in the design and conduct of clinical trials of biomedical HIV prevention and treatment approaches. After the meeting, a small group of organizers reviewed the presentations and feedback obtained during the meeting and categorized various lessons-learned to identify common themes. A group of 9 experts developed a draft summary of the findings that was circulated via email to all 46 attendees for review. Taking into account the feedback received, the group finalized the considerations that are presented here., Results: Meeting presenters and attendees discussed the many successful applications of digital technologies to improve research outcomes, such as those for recruitment and enrollment, participant identification, informed consent, data collection, data quality, and protocol or treatment adherence. These discussions also revealed unintended consequence of technology usage, including risks to study participants and risks to study integrity., Conclusions: Key lessons learned from these discussions included the need to thoroughly evaluate systems to be used, the idea that early success may not be sustained throughout the study, that some failures will occur, and considerations for study-provided devices. Additionally, taking these key lessons into account, the group generated recommendations on how to move forward with the use of technology in HIV vaccine and biomedical prevention trials., (©Jessica Andriesen, Sheana Bull, Janan Dietrich, Jessica E Haberer, Barbara Van Der Pol, Yegor Voronin, Kristin M Wall, Christopher Whalen, Frances Priddy. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 31.07.2017.)

Background: Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses., Methods: In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured., Results: The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration., Conclusion: Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses., Trial Registration: ClinicalTrials.gov NCT01264445.

Objective: The efficacy of pre-exposure prophylaxis (PrEP) in HIV will diminish with poor adherence; pharmacologic measures of drug exposure have proven critical to PrEP trial interpretation. We assessed drug exposure in hair against other pharmacologic and more routinely used measures to assess pill-taking., Design: Participants were randomized to placebo, daily PrEP, or intermittent PrEP to evaluate safety and tolerability of daily versus intermittent tenofovir/emtricitabine (TFV/FTC) in 2 phase II PrEP clinical trials conducted in Africa. Different measures of drug exposure, including self-report, medication event monitoring system (MEMS)-caps openings, and TFV/FTC levels in hair and other biomatrices were compared., Methods: At weeks 8 and 16, self-reported pill-taking, MEMS-caps openings, and TFV/FTC levels in hair, plasma, and peripheral blood mononuclear cells (PBMCs) were measured. Regression models evaluated predictors of TFV/FTC concentrations in the 3 biomatrices; correlation coefficients between pharmacologic and nonpharmacologic measures were calculated. Both trials were registered on ClinicalTrials.gov (NCT00931346/NCT00971230)., Results: Hair collection was highly feasible and acceptable (100% in week 8; 96% in week 16). In multivariate analysis, strong associations were seen between pharmacologic measures and MEMS-caps openings (all P < 0.001); self-report was only weakly associated with pharmacologic measures. TFV/FTC hair concentrations were significantly correlated with levels in plasma and PBMCs (correlation coefficients, 0.41-0.86, all P < 0.001)., Conclusions: Measuring TFV/FTC exposure in small hair samples in African PrEP trials was feasible and acceptable. Hair levels correlated strongly with PBMC, plasma concentrations, and MEMS-caps openings. As in other PrEP trials, self-report was the weakest measure of exposure. Further study of hair TFV/FTC levels in PrEP trials and demonstration projects to assess adherence/exposure is warranted.

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

Background: This mixed methods study reports on product acceptance from a Phase I clinical trial of a candidate non-nucleoside reverse transcriptase inhibitor (NNRTI) vaginal microbicide product (UC781). The product was evaluated in the context of a Phase I clinical trial in an area characterized by high HIV prevalence among minority women. The findings will inform the development of an acceptable microbicide that will address the needs of diverse women and their partners., Methods: This is a mixed methods study of 34 racially and ethnically diverse female participants and 10 male partners in Atlanta, Georgia. Chi-square tests for marginal homogeneity and kappa statistics were calculated to analyze differences between groups on product attributes and use intention. ANOVA was used to examine difference between the treatment groups. Qualitative data were analyzed via constant comparative methodology., Results: Thirty-four out of the original female cohort of 36 completed the questionnaire. Approval of future microbicide development was high at 91.2% (n=31) despite a lack of enthusiasm for the placebo and UC781 formulations. Overall female acceptability was correlated with personal protection motivation (r=1.00, p<0.001). African American women indicated greater likelihood of post-licensure microbicide use (X 2 (3) =7.9, p=0.048) and ascribed greater importance to its potential protection against HIV (X 2 (4) =18.7, p=0.001) and its potential for dual protection (protective against STIs and/or pregnancy) compared to white women (X 2 (4) =11.3, p=0.024). Men and women supported development in the form of an intravaginal ring or suppository. Men were more likely to encourage female adoption of the method if it afforded HIV protection (r=0.935, p=0.001)., Conclusions: Although most women agreed that the development of a microbicide was an important endeavor, quantitative and qualitative data indicated they would not use placebo or UC781 due to the objectionable viscosity, odor, and color. Male partners felt the potential protective benefit of a future microbicide product was its most important feature.

Standards of care provided to volunteers in HIV prevention research in developing countries are evolving. Inconsistency in standards, particularly within a research network highlights the need to balance volunteers' health and wellness with the efficient conduct of research. Ten research centers (RC's) in East and Southern Africa affiliated with the International AIDS Vaccine Initiative (IAVI) were studied using a mixed methods approach to understand variations, similarities and gaps in services provided, recipients of services, referral systems, and barriers to referral uptake. These data were then used to develop expected standards across the 10 RCs. Findings indicated that RCs consistently provided HIV risk reduction and family planning (FP) counseling, male condoms, management of sexually transmitted infections, CD-4 counts, and general medical care to volunteers and non-research volunteers. Services that were less consistently provided on-site included: female condoms, adult male circumcision (AMC), antiretroviral therapy (ART) and post-exposure prophylaxis (PEP) in case of rape. The FP options provided on-site varied, with few providing implants, intrauterine devices, tubal ligation, and vasectomy. Most RCs had established referral systems for ART, AMC, PEP, and FP, but few had referral points for psychosocial services. Few RCs had comprehensive guidelines on referrals other than those related to adverse events. Findings indicate that the greatest challenges for referral uptake were transportation and health care costs, poor quality and inconsistency of services at some referral points. Few RCs covered the cost of referrals for non-study related adverse events. A collaborative process between IAVI and the RCs was undertaken to reach consensus on expected standards of care. A set of required and recommended services to be provided on-site or by referral was developed. In developing such standards, we tried to balance scientific priorities, equity, contextual realities, community expectations, and cost-effectiveness.

While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2 × 2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present.

Background: With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries--worst affected by the HIV pandemic--have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001., Methodology: Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West., Principal Findings: Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrollment., Conclusions: Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants., Trial Registration: Protocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2](registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted.

A protective vaccine against HIV-1 will likely require the elicitation of a broadly neutralizing antibody (bNAb) response. Although the development of an immunogen that elicits such antibodies remains elusive, a proportion of HIV-1 infected individuals evolve broadly neutralizing serum responses over time, demonstrating that the human immune system can recognize and generate NAbs to conserved epitopes on the virus. Understanding the specificities that mediate broad neutralization will provide insight into which epitopes should be targeted for immunogen design and aid in the isolation of broadly neutralizing monoclonal antibodies from these donors. Here, we have used a number of new and established technologies to map the bNAb specificities in the sera of 19 donors who exhibit among the most potent cross-clade serum neutralizing activities observed to date. The results suggest that broad and potent serum neutralization arises in most donors through a limited number of specificities (1-2 per donor). The major targets recognized are an epitope defined by the bNAbs PG9 and PG16 that is associated with conserved regions of the V1, V2 and V3 loops, an epitope overlapping the CD4 binding site and possibly the coreceptor binding site, an epitope sensitive to a loss of the glycan at N332 and distinct from that recognized by the bNAb 2G12 and an epitope sensitive to an I165A substitution. In approximately half of the donors, key N-linked glycans were critical for expression of the epitopes recognized by the bNAb specificities in the sera.

Background: The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines. Despite its excellent safety record, some cases of viscerotropic adverse events develop, which are sometimes fatal. The mechanisms underlying such events remain a mystery. Here, we present an analysis of the immunologic and genetic factors driving disease in a 64-year-old male who developed viscerotropic symptoms., Methods: We obtained clinical, serologic, virologic, immunologic and genetic data on this case patient., Results: Viral RNA was detected in the blood 33 days after vaccination, in contrast to the expected clearance of virus by day 7 after vaccination in healthy vaccinees. Vaccination induced robust antigen-specific T and B cell responses, which suggested that persistent virus was not due to adaptive immunity of suboptimal magnitude. The genes encoding OAS1, OAS2, TLR3, and DC-SIGN, which mediate antiviral innate immunity, were wild type. However, there were heterozygous genetic polymorphisms in chemokine receptor CCR5, and its ligand RANTES, which influence the migration of effector T cells and CD14+CD16bright monocytes to tissues. Consistent with this, there was a 200-fold increase in the number of CD14+CD16bright monocytes in the blood during viremia and even several months after virus clearance., Conclusion: In this patient, viscerotropic disease was not due to the impaired magnitude of adaptive immunity but instead to anomalies in the innate immune system and a possible disruption of the CCR5-RANTES axis.

The potential medical transmission of HIV through unsafe medical injections was evaluated in 16 rural health institutions in Ethiopia. Most institutions reported re-using disposable needle/syringes, and 12% of observed injections were given with used, disposable syringes prepared for re-use. Analysis of used needle flushes showed no HIV RNA; however, the sensitivity of our method was limited. Despite the re-use of disposable needles, medical injection practices are not likely to contribute significantly to HIV transmission in this region.

Objective: Voluntary HIV testing and counseling (VTC) has been shown to reduce the incidence of HIV in cohabiting couples who now represent the majority of new infections in many African cities. Community and client perceptions of a 1-day voluntary testing and counseling program in Lusaka, Zambia, were assessed, and a rapid HIV-testing algorithm was evaluated for VTC centers., Methods and Design: Between May 1995 and June 1996, outreach workers distributed written invitations door to door. The 1-day program was held 6 days/week including weekends. Transport, child care and lunch were provided. Community and client surveys followed in July 1996., Results: Over 3500 couples married for a median of 4-5 years requested testing: 23% were HIV+/+, 57% were HIV-/- and 20% were discordant with one HIV+ and one HIV- partner. Sixty-eight per cent of couples surveyed had made the decision to be tested before attending the 1-day program and 80% had not previously known where to obtain HIV testing. Knowledge that couples could show discordant results rose from 29 before to 88% after pretest counseling. Clients reported high levels of satisfaction with the services and 90 out of 99 (92%) preferred to receive their results the same day. Clients at another center who waited 10 days for their results reported more fear, and 19 out of 31 (61%) would have preferred to get their results the same day. Over 99% of those who attended the program thought active promotion of voluntary HIV testing in the community was a positive thing, as did 90% of those who were invited but did not attend. Sensitivity and specificity of the rapid test algorithm were both 99.4% in this setting., Conclusions: Active promotion of voluntary HIV testing and counseling in couples is needed to reduce the spread of HIV in high-prevalence areas. The use of rapid, on-site HIV testing allows clients to receive result-specific counseling in a single visit. Ongoing quality control of a subset of samples at an outside laboratory is essential.

In critically ill patients, the inaccuracy of predictive formulas for nutritional assessment often leads to inappropriate and potentially detrimental feeding regimens. This study evaluates the clinical utility of the metabolic cart in an urban university hospital setting. Twenty-six studies were performed on each of 26 patients (18 surgical, 8 medical) using an MMC Horizon metabolic cart. Although 58% of patients were overweight, 42% were still shown to have a kwashiorkorlike pattern of malnutrition. Three patients demonstrated a marasmic-like pattern. Fifteen percent of studies showed patients to be hypometabolic and 62% hypermetabolic. Harris-Benedict resting energy expenditure, based on actual or ideal body weight, underestimated needs; however, addition of a metabolic activity factor overestimated needs. Only 32% of patients were fed appropriately; 41% were underfed, and 27% were overfed. Urine area nitrogen correlated poorly with energy expenditure. Measured RQ appropriately reflected substrate utilization in 77% of studies; multiple factors may have caused differences between measured and predicted RQ in 23%. Use of the metabolic cart determines precisely the metabolic state, identifies problems with substrate utilization, and enables the physician to design the most efficacious nutritional regimen.

Abortion rates rose following the expanded legalization of abortion by the Supreme Court decision in Roe v. Wade. As a result, the impact of the restriction on Federal funding of abortions under the Hyde Amendment in 1977 was not clear. However, abortion rates had plateaued by 1985, when State funding of Medicaid abortions was restricted in Colorado, North Carolina, and Pennsylvania. Analysis of statewide data from the three States indicated that following restrictions on State funding of abortions, the proportion of reported pregnancies resulting in births, rather than in abortions, increased in all three States. In 1985, the first year of State restrictions on the use of public funds for abortion, Colorado, North Carolina, and Pennsylvania recorded 1.9 to 2.4 percent increases in the proportion of reported pregnancies resulting in live births, after years of declining rates. With adjustments for underreporting of abortion, there was an overall 1.2 percent rise in the proportion of pregnancies resulting in live births in those States. Nationally the proportion rose only 0.4 percent. By 1987, the three States had experienced increases above 1984 levels of 1.6 to 5.9 percent in the proportion of reported pregnancies resulting in live births. The experiences of the three States can be used in projecting an expected increase in the proportions of reported pregnancies resulting in live births, rather than in abortions, for similar States. A projection for California, for example, showed that an increase could be expected in the first year of restrictions on the use of public funds for abortion of at least 4,000 births, which could be expected largely to affect women of low income.