Scott Hammer

• Columbia University

Background: VRC01, a potent, broadly-neutralizing monoclonal antibody, inhibits simian-HIV infection in animal models. HVTN 104 assessed VRC01 safety and pharmacokinetics in humans. We extend the clinical evaluation to determine intravenous-infused VRC01 distribution and protective function at mucosal sites of HIV-1 entry. Methods: Healthy, HIV-...

Background α4β7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4β7 expressing CD4⁺ T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown i...

Purpose: To lower the HIV risk of transgender women, it is imperative to understand their unique HIV prevention needs and design biomedical prevention interventions that are responsive to the psychosocial, behavioral, and clinical needs of these communities. Preventive HIV vaccines are an important modality under investigation in diverse study part...

HVTN 505 is a preventative vaccine efficacy trial testing DNA followed by recombinant adenovirus serotype 5 (rAd5) in circumcised, Ad5-seronegative men and transgendered persons who have sex with men in the United States. Identified immune correlates of lower HIV-1 risk and a virus sieve analysis revealed that, despite lacking overall efficacy, vac...

By analyzing data from the HVTN 505 efficacy trial of a DNA/recombinant adenovirus 5 (rAd5) vaccine regimen, we found that host genetics, specifically Fc gamma receptor genetic variations, influenced whether receiving the DNA/rAd5 regimen was beneficial, neutral, or detrimental to an individual with respect to HIV-1 acquisition risk. Moreover, Fc g...

Background: HVTN 505 was an HIV-1 preventive vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured one month post-final vaccination (Month 7) as correlates of HIV-1 acquisition risk. Methods: Binding antibody responses were quantified in serum samples from 25 primary end...

Mean time since infection and antibody testing. Numbers of participants with primary endpoint HIV-1 infection included in the sieve analysis, mean time between HIV-1 infection and sampling for HIV-1 sequencing, and antibody testing. (PDF)

Non-conserved cysteine residue frequencies in mindist sequences. Subtype B viruses typically possess 18 cysteine residues forming 9 disulfide bridges in gp120 and 2 cysteine residues in gp41 forming an additional disulfide bridge for a total of 20 conserved cysteine residues. These residues are also conserved in the mindist sequences for both treat...

Comparison of pairwise and tree-based distance measures across treatment groups using Env-gp120 alignments without variable segments. Distances correspond to the tree-based amino acid distance between the vaccine inserts or HIV-1 references and the breakthrough sequences from a given subject. Comparisons between vaccine and placebo groups were done...

Percentage of CTL epitopes predicted among breakthrough sequences that were matched to HIV-1 reference sequences. Epitopes predicted in breakthrough sequences were matched against epitopes derived from reference sequences when there were no more than 3 mutations between the 9mers. (PDF)

Comparison of evolutionary distances for predicted CTL epitopes from vaccine and placebo recipients. Epitopes predicted to be strong and weak binders were matched against vaccine inserts or HIV-1 reference sequences and evolutionary distances were computed between breakthrough virus-derived epitopes and vaccine or reference-derived epitopes. The di...

Comparison of pairwise distance measures across treatment. Mean divergence measures were calculated based on pairwise amino acid distances between the vaccine inserts or HIV-1 references and all sequences from a given subject. Comparisons between vaccine and placebo groups were done using a Wilcoxon rank sum test (Mann-Whitney test) with exact 2-si...

HIV-1 Env sites under positive selection in the vaccine group only. Eight sites were identified in Env-gp120 using three methods. (PDF)

Monoclonal antibody contact set scanning. Results of the mAb contact set scanning analysis grouped by monoclonal antibody class (CD4bs, CD4i, and V3, Quarternary, gp41 MPER, gp41 NHR, gp41 cluster II, and Glycan) and ranked within class by P-value. The effect size is measured in additional mismatch rate in the vaccine group per contact site where a...

Results of machine learning sieve analysis. Results for the area under the ROC curve (AUC) and classification accuracy (ACC) on held-out data for the four machine learning methods applied over the different regions of the HIV-1 genome. The “region” column indicates the region of the protein for which AA sites were included in the analysis. A null r...

Monoclonal antibody contact site sets. (XLSX)

Mindist sequence cysteine counts. (A) Cysteine counts of gp160 mindist sequences by treatment group. P-values compare counts by treatment using a two-sample t-test. (B) A total of twenty cysteines in gp160 were found in all mindist sequences consisting of 9 pairs in gp120 and 1 pair in gp41. At least one additional cysteine was found in each of the...

Amino acid distributions for 9-mer Env 365–373. The amino acid (AA) distribution for linear signature region Env-gp120 AA365-373 by treatment group for all breakthrough sequences. Each row displays the AA distribution for one site relative to the VRC-B vaccine strain AA. Sequences for each participant are represented by a bar of equal height with t...

Comparison of intra-host diversity measures across treatment groups. Intra-host mean diversity measures were computed based on pairwise amino acid distances between all sequences from a given subject. Comparisons between vaccine and placebo groups were done using a Wilcoxon rank sum test (Mann-Whitney test) with exact 2-sided p-value. Multiplicity...

Comparison of evolutionary distances for predicted CTL epitopes (strong binders only) from vaccine and placebo recipients. Epitopes predicted to be strong binders were matched against vaccine inserts or HIV-1 reference sequences and evolutionary distances were computed between breakthrough virus-derived epitopes and vaccine- or reference-derived ep...

Comparison between the vaccine and placebo groups for 19 Env-gp120 CTL epitopes. Only epitopes that were identified in at least three vaccine and three placebo recipients were considered for comparison through Mann-Whitney tests. Mean values corresponding to all subjects in each group are reported; for a given subject, the binding affinity or evolu...

Amino acid distributions for K-mer region Env 192–207. The amino acid (AA) distribution for linear signature region Env-gp120 AA192-207 by treatment group for all breakthrough sequences. Each row displays the AA distribution for one site relative to the VRC-B vaccine strain AA. Sequences for each participant are represented by a bar of equal height...

Amino acid distributions for K-mer region Env 425–437. The amino acid (AA) distribution for linear signature region Env-gp120 AA425-437 by treatment group for all breakthrough sequences. Each row displays the AA distribution for one site relative to the VRC-B vaccine strain AA. Sequences for each participant are represented by a bar of equal height...

Percent epitope mismatch analysis. Percent epitope mismatch based on (A) netMHCpan and (B) ADT. For Env, predicted weak binders to all 9-mers from the three vaccine insert sequences (VRC-A, VRC-B, and VRC-C) combined were used to determine the percent epitope mismatch. Similarly, percent epitope mismatch was computed using all of the non-insert gen...

Additional information on HIV-1 sequences, sequence analysis, CTL epitope predictions, site scanning methods, machine learning highly multivariable sieve analysis, antibody-dependent cellular phagocytosis (ADCP), and references. (DOCX)

Comparison of tree-based distance measures across treatment. Mean divergence measures were calculated based on tree-based amino acid distances between the vaccine inserts or HIV-1 references and all sequences from a given subject. Comparisons between vaccine and placebo groups were done using a Wilcoxon rank sum test (Mann-Whitney test) with exact...

Site scanning signatures. Site and method for each site scanning result with a Q-value ≤ 0.2. N is the number of AA sites included for each multiple comparison. The Direction (+ for more or–for fewer mismatches in vaccine than placebo sequences) of the effect is with respect to the subtype B vaccine insert for Env, the vaccine insert for Pol and Ne...

Comparison of binding affinity measures for predicted CTL epitopes from vaccine and placebo recipients. Epitopes predicted to be strong and weak binders were matched against vaccine inserts or HIV-1 reference sequences and the predicted binding affinity of breakthrough virus-derived epitopes were compared to those of vaccine- and reference-derived...

Comparison of binding affinity measures for predicted CTL epitopes (strong binders only) from vaccine and placebo recipients. Epitopes predicted to be strong binders were matched against vaccine inserts or reference sequences and the predicted binding affinity of breakthrough virus-derived epitopes were compared to those of vaccine- or reference-de...

Amino acid distributions for K-mer region Env 27–37. The amino acid (AA) distribution for linear signature region Env-gp120 AA27-37 by treatment group for all breakthrough sequences. Each row displays the AA distribution for one site relative to the VRC-B vaccine strain AA. Sequences for each participant are represented by a bar of equal height wit...

Amino acid distributions for K-mer region Env 464–478. The amino acid (AA) distribution for linear signature region Env-gp120 AA464-478 by treatment group for all breakthrough sequences. Each row displays the AA distribution for one site relative to the VRC-B vaccine strain AA. Sequences for each participant are represented by a bar of equal height...

Amino acid distributions for 9-mer Env 86–94. The amino acid (AA) distribution for linear signature region Env-gp120 AA86-94 by treatment group for all breakthrough sequences. Each row displays the AA distribution for one site relative to the VRC-B vaccine strain AA. Sequences for each participant are represented by a bar of equal height with the r...

Antibody-dependent cellular phagocytosis (ADCP) activity of antibodies induced by the DNA/rAd5 vaccine regimen at (A) baseline and (B) 4 weeks post-4th vaccination. Neutravidin fluorescent beads were coated with a biotinylated HIV-1 antigen (ConSgp140), then incubated with monoclonal antibodies (positive control CH31 and negative control CH65) or I...

Background It is important to identify vaccine-induced immune responses that predict the preventative efficacy of an HIV-1 vaccine. We assessed T cell response markers as potential correlates of risk in the HVTN 505 HIV-1 vaccine efficacy trial. Methods 2504 participants were randomized to DNA/rAd5 vaccine or placebo, administered at weeks 0, 4, 8...

Background: Cardiovascular disease (CVD) is a leading health threat for HIV+ patients on antiretroviral therapy (ART); cardiometabolic comorbidities are key predictors of risk. Data are limited on incidence of metabolic comorbidities in HIV+ individuals initiating ART in low and middle income countries (LMICs), particularly for Hispanics. We exami...

Data Underlying Findings Reported in Manuscript. Variable definitions are included in second sheet. (XLSX)

The World Health Organization has issued an early release revision to its antiretroviral guidelines in which PrEP (Pre-exposure prophylaxis in the form of daily oral, fixed dose combination tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)) is recommended as a prevention option to all people at substantial risk of acquiring HIV. However, lack o...

In the last 15 years, antiretroviral therapy (ART) has been the most globally impactful life-saving development of medical research. Antiretrovirals (ARVs) are used with great success for both the treatment and prevention of HIV infection. Despite these remarkable advances, this epidemic grows relentlessly worldwide. Over 2.1 million new infections...

Background: Increasing the breadth of HIV vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HVTN 083 tested whether cellular immune responses with these features are induced by prime-boost strategies employing heterologous vectors, heterologous inserts, or a combination of both. Methods:...

Background: Three phase 2b, double-blind, placebo-controlled, randomized efficacy trials have tested recombinant Adenovirus serotype-5 (rAd5)-vector preventive HIV-1 vaccines: MRKAd5 HIV-1 gag/pol/nef in Step and Phambili, and DNA/rAd5 HIV-1 env/gag/pol in HVTN505. Due to efficacy futility observed at the first interim analysis in Step and HVTN505...

An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1–reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1–reactive A...

The field of HIV prevention research has recently experienced some mixed results in efficacy trials of pre-exposure prophylaxis, vaginal microbicides, and HIV vaccines. While there have been positive trial results in some studies, in the near term, no single method will be sufficient to quell the epidemic. Improved HIV prevention methods, choices a...

The governors of a number of states, including New York and New Jersey, recently imposed 21-day quarantines on health care workers returning to the United States from regions of the world where they may have cared for patients with Ebola virus disease. We understand their motivation for this policy - to protect the citizens of their states from con...

HVTN 505, a phase 2b trial assessing if a DNA/rAd5 HIV vaccine prime/boost regimen reduces HIV acquisition or viremia post infection, halted vaccinations in 2013 due to efficacy futility, even though it induced substantial CD8+ T-cell responses. We examined whether vaccine-induced T cells lack the capacity to inhibit virus replication as a potentia...

Finding an effective human immunodeficiency virus type 1 (HIV-1) vaccine remains a major global health priority. In a phase I/II, placebo-controlled trial, healthy, HIV-1-negative adults were randomized to receive one of 5 vaccine regimens: LIPO-5 (combination of 5 lipopeptides) alone (250 mu g), ALVAC-HIV (vCP1452) alone, or 3 groups of ALVAC-HIV...

Background Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure. Methods This multicenter, prospective study...

Abstract Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and...

The 17th Conference on Retroviruses and Opportunistic Infections maintained its tradition of being the preeminent forum for detailing the state-of-the-art of antiretroviral therapy. Abundant new and updated information was presented on investigational drugs, approaches to the management of treatment-naive and -experienced patients, the use of drugs...

Background: Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected adults for safety, immunogenicity, and 6-month durability of immune responses. Methods: A to...

The durable suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA that is conferred by potent antiretroviral therapy (ART) has been associated with dramatic improvements in immunologic and clinical well-being and reductions in morbidity and mortality from opportunistic complications. It has also brought the restoration of normal lif...

Background: 0.5% to 10% of clean surgeries result in surgical-site infections, and attempts to reduce this rate have had limited success. Germicidal UV lamps, with a broad wavelength spectrum from 200 to 400 nm are an effective bactericidal option against drug-resistant and drug-sensitive bacteria, but represent a health hazard to patient and staf...

BackgroundA safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States. Methods At 21 sites, we randomly assigned...

Background: Cardiovascular disease is an increasingly recognized complication of chronic HIV infection, yet little is known about the disease burden of its common precursors: impaired fasting glucose (IFG), diabetes (DM), and overweight/obesity, in HIV+ people in resource limited settings. Prevalence of DM (7%) and obesity (11% in men and 39% in wo...

In November 2010, the iPrEx study reported that preexposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January to March 2011, part...

The development of a safe and effective HIV vaccine remains a challenge. The modest efficacy seen in the RV144 vaccine trial represented an important milestone for the field. Results from all efficacy studies done to date have generated new information, which has advanced the HIV vaccine field in important ways. In this article, we review the trans...

The HIV prevention landscape is evolving rapidly, and future efficacy trials of candidate vaccines, which remain the best long-term option for stemming the HIV epidemic, will be conducted in the context of partially effective non-vaccine prevention modalities. It is essential that these trials provide for valid and efficient evaluation of vaccine e...

Background: While persistent T-cell activation has been cross-sectionally associated with poor CD4+ T-cell restoration in HIV-infected individuals maintaining antiretroviral treatment (ART)-mediated viral suppression, it remains unclear whether CD8+ T-cell activation is of predictive effect on CD4+ T-cell recovery. Objective: We assessed whether...

The 20th Conference on Retroviruses and Opportunistic Infections (CROI) presented important highlights of advances in antiretroviral therapy. Investigators emphasized new approaches to finding a cure for HIV infection, with a special focus on an infant who received combination antiretroviral therapy at 30 hours of age and may have achieved a functi...

New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings. To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools....

The 19th Conference on Retroviruses and Opportunistic Infections (CROI) highlighted new information and provided in-depth discussion on advances in antiretroviral therapy (ART). Data regarding investigational drugs, including integrase strand transfer inhibitors (InSTIs) and zinc-finger nucleases disrupting CC chemokine receptor 5 (CCR5), were pres...

The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementa...

We previously demonstrated in vitro that zidovudine (AZT) selects for A371V in the connection domain and Q509L in ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) which, together with the thymidine analog mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. The goal of the current study was to determine wh...

AIDS Clinical Trials Group Study 175 Protocol Team. (DOCX)

Five preventative HIV vaccine efficacy trials have been conducted over the last 12 years, all of which evaluated vaccine efficacy (VE) to prevent HIV infection for a single vaccine regimen versus placebo. Now that one of these trials has supported partial VE of a prime-boost vaccine regimen, there is interest in conducting efficacy trials that simu...

Emergence of HIV resistance is a concerning consequence of global scale-up of antiretroviral therapy (ART). To date, there is no published information about HIV resistance from the Dominican Republic. The study's aim was to determine the prevalence of transmitted drug resistance (TDR) to reverse transcriptase and protease inhibitors in a sample of...

The 18th Conference on Retroviruses and Opportunistic Infections maintained its tradition of being the preeminent forum for detailing the state-of the-art in antiretroviral therapy. There were important presentations on investigational antiretroviral drugs, clinical trials in treatment-experienced patients, and new antiretroviral strategies. Releva...

The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 H...

Recently, the RV144 randomized, double-blind, efficacy trial in Thailand reported that a prime-boost human immunodeficiency virus (HIV) vaccine regimen conferred ∼30% protection against HIV acquisition. However, different analyses seemed to give conflicting results, and a heated debate ensued as scientists and the broader public struggled with thei...

We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was asso...

A safe and effective HIV vaccine is needed to curtail the US and global epidemics. However, the search for one has been elusive despite more than 25 years of focused research. Results from the RV144 Thai efficacy trial have renewed hope that a vaccine may protect against HIV acquisition. We can draw several scientific and operational lessons from R...

Abstract The safety and immunogenicity of the MRK adenovirus type 5 (Ad5) HIV-1 clade B gag vaccine was assessed in an international Phase I trial. Three-hundred and sixty healthy HIV-uninfected adults were enrolled on five continents. Subjects received placebo or 1 × 10(9) or 1 × 10(10) viral particles (vp) per dose of the MRKAd5 HIV-1 gag vaccine...

Purpose: There are growing concerns of cardiovascular disease in HIV-infected individuals and in developing countries, such as Thailand. We described the ten-year risk of coronary heart disease (CHD) in a Thai HIV-infected cohort using 3 cardiovascular risk equations, and assessed the level of agreement between their predictions. Methods: Cross-sec...

Maximizing the durability of viral suppression is a key goal of antiretroviral therapy. The objective of AIDS Clinical Trials Group Study 372A was to determine whether the intensification strategy of adding abacavir to an effective indinavir-dual nucleoside regimen would delay the time to virologic failure. Zidovudine-experienced subjects (n=229) o...

Recent data regarding the consequences of untreated human immunodeficiency virus (HIV) infection and the expansion of treatment choices for antiretroviral-naive and antiretroviral-experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adults with HIV infection. To provide upd...

The contribution of low frequency drug-resistant human immunodeficiency virus type 1 (HIV-1) variants to failure of antiretroviral therapy is not well defined in treatment-experienced patients. We sought to detect minor nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistant variants at the initiation of multidrug efavirenz-containing thera...

Limited data are available on circumcision prevalence and acceptability among Thai men to prevent human immunodeficiency virus. Of 408 high-risk heterosexual men, 12.3% were circumcised. 14.2% and 24.9% expressed willingness to be circumcised before and after circumcision education, respectively. Neonatal circumcision acceptability was relatively h...

Context: Low bone mineral density (BMD) is commonly reported in young men and women with HIV infection, and fracture rates may be higher. With effective antiretroviral therapy (ART), the HIV population is aging. However, little is known about the skeletal status of postmenopausal women. Objective: We aimed to assess the effects of HIV infection...

This study analyzes immunologic markers to predict and diagnose tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV and TB coinfected adults who initiated antiretroviral therapy (ART) in Thailand. T helper 1 cytokines interleukin (IL)-2, IL-12, and interferon-gamma (IFN-gamma) levels in response to PPD and RD1 antig...