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Recall and social desirability bias undermine self-report of paper-and-pencil questionnaires. Mobile phone questionnaires may overcome these challenges. We assessed and compared sexual risk behavior reporting via in-clinic paper-and-pencil and mobile phone questionnaires. HVTN 915 was a prospective cohort study of 50 adult women in Soweto, who completed daily mobile phone, and eight interviewer-administered in-clinic questionnaires over 12 weeks to assess sexual risk. Daily mobile phone response rates were 82% (n = 3486/4500); 45% (n = 1565/3486) reported vaginal sex (median sex acts 2 (IQR: 1-3)) within 24 h and 40% (n = 618/1565) consistent condom. Vaginal sex reporting was significantly higher via mobile phone across all visits (p < 0.0001). There was no significant difference in condom use reporting by mobile phone and in-clinic paper-based questionnaires across all visits (p = 0.5134). The results show high adherence and reporting of sex on the mobile phone questionnaire. We demonstrate feasibility in collecting mobile phone sexual risk data. [ABSTRACT FROM AUTHOR]

Background. Coinfection with human immunodeficiency virus (HIV) may increase susceptibility to malaria by compromising naturally acquired immunity.Methods. In 339 adults (64% HIV infected), we measured antibodies to Plasmodium falciparum variant surface antigens (VSA) and antibodies that opsonise infected erythrocytes using parasite lines FCR3, E8B, and R29, and antibodies to merozoite antigens AMA-1 and MSP2. We determined the relationship between malaria antibodies, HIV infection, markers of immune compromise, and risk of incident parasitemia.Results. HIV-infected adults had significantly lower mean levels of opsonizing antibody to all parasite lines (P < .0001), and lower levels of antibody to AMA-1 (P = .01) and MSP2 (P < .0001). Levels of immunoglobulin G (IgG) to VSA were not affected by HIV status. Opsonising antibody titres against some isolates were positively correlated with CD4 count. There were negative associations between human immunodeficiency virus type 1 (HIV-1) viral load and opsonizing antibodies to FCR3 (P = .04), and levels of IgG to AMA-1 (P ≤ .03) and MSP2-3D7 (P = .05). Lower opsonizing antibody levels on enrollment were seen in those who became parasitemic during follow-up, independent of HIV infection (P ≤ .04 for each line).Conclusions. HIV-1 infection decreases opsonizing antibodies to VSA, and antibody to merozoite antigens. Opsonizing antibodies were associated with lack of parasitemia during follow up, suggesting a role in protection. [ABSTRACT FROM AUTHOR]

By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January–September 2007. Motivations for trial enrolment, social harms, adverse events and loss to follow-up were compared between younger (18–20 years old) and older participants (21–35 years old). Both younger (n = 238) and older participants (n = 563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p = 0.005), while younger males were more likely to enrol because the vaccine may provide protection from HIV-acquisition (p < 0.001). There were no significant differences in the number of social harms reported. Compared to males over 20 years old, 18–20-year-old females were less likely to experience adverse events (OR = 0.1, CI 0.01–0.80) and no more likely to be lost to follow-up (OR = 0.7, CI 0.39–1.25), while 18–20-year-old males were no more likely to experience adverse events (OR = 1.3, CI 0.58–2.83) or loss to follow-up (OR = 0.8, CI 0.51–1.41). Our data support the inclusion of younger participants who are at risk for HIV in future HIV vaccine efficacy trials. [ABSTRACT FROM AUTHOR]

The progress on COVID-19 vaccines should lead to progress on HIV and TB vaccines. It may be years before we identify the most important scientific contributions from the responses to the SARS-CoV-2 pandemic to the future of HIV and TB vaccine research. Individual investigators achieved basic discoveries, making subsequent advances to develop COVID-19 vaccines possible in a year; then multinational clinical trial networks initially established for HIV vaccine research enabled Phase 3 efficacy testing. Keywords: HIV; TB; COVID-19; vaccine; translational medical research; citizen science EN HIV TB COVID-19 vaccine translational medical research citizen science 1 2 2 06/05/21 20210501 NES 210501 As contagion of sickness makes sickness, contagion of trust can make trust. [Extracted from the article]

Background: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. Methods: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. Results: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)]. Conclusions: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention. [ABSTRACT FROM AUTHOR]

Background. We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines. Methods. Healthy HIV-uninfected adults were enrolled in 6 blinded placebo-controlled studies evaluating the immunogenicity of (1) a 4-dose regimen of a DNA vaccine, (2) a 3-dose priming regimen of the DNA vaccine with a booster dose of an adenovirus type 5 (Ad5)-vectored vaccine, or (3) a 3-dose regimen of the Ad5 vaccine. The DNA plasmid was provided with or without an aluminum phosphate or CRL1005 adjuvant. The primary end point was the unfractionated HIV-1 gag-specific interferon γ enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose. Results. Overall, 254 (83%) of 307 subjects randomized to the vaccine groups were evaluable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5-containing regimens than for the DNA/DNA regimen (33%) but were similar for DNA/Ad5 (55%) and Ad5/Ad5 (50%). DNA/DNA elicited mainly a CD4 response, whereas Ad5/Ad5 elicited mainly a CD8 response; DNA/Ad5 generated CD4 and CD8 responses comparable to those of DNA/DNA and Ad5/Ad5, respectively. Conclusions. The DNA vaccine alone or as a priming regimen for the Ad5 vaccine did not increase unfractionated ELISpot responses compared with the Ad5 vaccine alone. Qualitative T cell responses to different vaccine regimens deserve further study. [ABSTRACT FROM AUTHOR]

Background. The safety and immunogenicity of the MRK adenovirus type 5 human immunodeficiency virus type 1 clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5-vectored vaccine designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial. Methods. Healthy adults not infected with human immunodeficiency virus were enrolled in a multicenter, dose-escalating, blind, placebo-controlled study to evaluate a 3-dose homologous prime-boost regimen of the trivalent MRK adenovirus type 5 human immunodeficiency virus type 1 vaccine containing from 3×106 to 1×1011 viral particles per 1-mL dose administered on day 1, during week 4 and during week 26. Adverse events were recorded for 29 days after each intradeltoid injection. The primary immunogenicity end point was the proportion of study participants with a positive unfractionated Gag-, Pol-, or Nef-specific interferon-g enzymelinked immunosorbent spot response measured 4 weeks after administration of the last dose. Results. Of 259 randomized individuals, 257 (99%) received ≥1 dose of vaccine or placebo and were included in the safety analyses. Enzyme-linked immunosorbent spot results were available for 217 study participants (84%) at week 30. No serious vaccine-related adverse events occurred. No study participant discontinued participation because of vaccine-related adverse events. The frequency of injection-site reactions was dose dependent. Vaccine doses of ≥3×109 viral particles elicited positive enzyme-linked immunosorbent spot responses to ≥1 vaccine component in 160% of recipients. High baseline antibody titers against adenovirus type 5 diminished enzymelinked immunosorbent spot responses at all doses except the 3×1010 viral particle dose. Conclusions. The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy. [ABSTRACT FROM AUTHOR]

Background. The genetic diversity of human immunodeficiency virus type 1 (HIV- 1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV- 1 T cell responses to the infecting HIV- 1 clade relative to other major circulating clades. Methods. Cellular immune responses to HIV- 1 clades A, B, and C were compared by standardized interferon- y enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV- 1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV- 1. Results. Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV- 1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62- 0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P < .0001). Conclusions. Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein. [ABSTRACT FROM AUTHOR]

Presents a prospective study conducted to measure the selective effect of pyrimethamine prophylaxis on point mutations in Plasmodium falciparum dihydrofolate reductase (DHRF). Analysis of P. falciparum infections by polymerase chain reaction; Absence of evidence of clonal identity among baseline and breakthrough infections; Selectiveness for DHFR mutations by pyrimethamine.

Background. HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8+ T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent. Methods. Viral loads, CD4+ T-cell counts, and enzyme-linked immunospot assay–determined anti-HIV-1 CD8+ T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed. Results. Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P = .01), a 0.76 log10 lower longitudinal viremia level (P = .01), and slower progression to a CD4+ T-cell count of <350 cells/mm3 (P = .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses; P = .04) and magnitude (2300 vs 70 spot-forming cells/106 peripheral blood mononuclear cells; P = .06) in vaccinees versus placebo recipients. Conclusions. In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4+ T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition. Clinical Trials Registration. NCT00413725, DOH-27-0207-1539.

Engagement of early stage investigators (ESIs) in the search for a safe and effective vaccine is critical to the success of this highly challenging endeavor. In the wake of disappointing results from a large-scale efficacy trial, the HIV Vaccine Trials Network (HVTN) and Center for HIV/AIDS Vaccine Immunology (CHAVI) developed a novel mentored research program focused on the translation of findings from nonhuman primate studies to human trials of experimental vaccines. From 2008 to 2011, 14 ESI Scholars were selected from 42 complete applications. Post program surveys and tracked outcomes suggest that the combination of flexible funding, transdisciplinary mentorship, and structured training and networking promoted the scientific contributions and career development of promising ESIs. Embedding a multicomponent research program within collaborative clinical trial networks and research consortia is a promising strategy to attract and retain early career investigators and catalyze important translational science. [ABSTRACT FROM AUTHOR]