Substance Use and Testing Sexual Partners Using HIV Self-tests.

HIV self-tests (HIVST) provide the possibility of testing partners prior to sexual activity. This study examines the role of substance use among men who have sex with men (n = 123) and transgender women (n = 13) who were provided HIVST to use with potential sex partners. Several reported avoiding/delaying alcohol (44%) or drug use (27%) because they intended to use HIVST. Those who used HIVST with alcohol (37%) or drugs (24%) did not differ from those who did not on number of partners asked, proportion who agreed, or intentions to use HIVST. A minority reported problems caused by substances. Ten did not ask someone to test because they were too drunk/high. Fourteen said it was fairly or very hard to use HIVST when under the influence. Eleven reported substances caused problems when discussing or administering HIVST, but only two of those felt the problems were major.

Then We Looked at His Results: Men Who Have Sex With Men from New York City and Puerto Rico Report Their Sexual Partner's Reactions to Receiving Reactive HIV Self-Test Results.

Secondary distribution of HIV self-tests to sexual partners is acceptable but concerns remain about reactions if a partner tests HIV-positive. We report on 14 participants whose sexual partners tested HIV-positive during the "I'll Show You Mine" Study, a randomized controlled trial (N = 272) of HIV self- and partner-testing among men who have sex with men (MSM) and transgender women (TGW). All 14 were MSM and racial/ethnic minorities, mean age was 36.6 years; 86% were gay-identified. Twenty-four partners tested positive; about half were new partners. Six participants had multiple partners test positive. During in-depth interviews with 10 of these participants, they reported their partners' reactions ranged from tearful and worried among those whose result was unexpected, to resignation among those who suspected a positive result, to nonchalance among partners who participants concluded knew of their HIV infection. After testing, some HIV-positive partners disclosed prior knowledge of their status. No partner reacted violently. Participants typically comforted their partners and encouraged confirmatory testing. Four participants had anal intercourse with partners who tested positive. Participants and partners were able to effectively handle situations in which the partner tested HIV-positive.

Use of Rapid HIV Self-Test to Screen Potential Sexual Partners: Results of the ISUM Study.

ISUM ("I'll show you mine") was a randomized controlled trial in which 272 transgender women and men who have sex with men in New York, NY (NYC) and San Juan, Puerto Rico (SJU) were assigned to an intervention group (n = 136), in which they had access to free HIV self-testing (ST) kits, or to a control group (n = 136). The trial aimed to determine whether the intervention group would use ST to screen sexual partners and have fewer condomless anal intercourse (CAI) occasions with serodiscordant or unknown status partners than the control group. The intervention group had on average 10 (32%) fewer CAI occasions; though clinically relevant, this difference fell short of statistical significance (p = .08). In NYC (n = 166) intervention participants had significantly fewer CAI occasions, whereas in SJU (n = 106) they reported non-significantly more CAI occasions. Two devastating hurricanes hit SJU during the study and may have impacted results in unmeasured ways.

Using an HIV Self-test Kit to Test a Partner: Attitudes and Preferences Among High-Risk Populations.

For those most at risk of contracting HIV, new strategies for preventing transmission and increasing testing are needed. As part of a multi-site, randomized, controlled trial, we explored attitudes and preferences among 272 HIV-negative men who have sex with men and HIV-negative transgender women using an HIV self-testing (HIVST) kit to test partners. Less than one quarter had previously self-tested with HIVST kits (21.7%) and few had partner-tested (4.8%). Most preferred gum swab (96%) over fingerprick tests (69%), but would prefer a blood test if it gave results for other sexually transmitted infections (STIs) (86%). Five percent reported difficulties performing the test, four percent with storage, and 26% with portability. Ninety-three percent reported likelihood of using HIVST to test partners in future, but only 3% were willing to pay the current price. Efforts to improve HIVST uptake should focus on incorporating testing for other STIs, reducing test kit size, and reducing cost.

RESUMEN: Se necesitan nuevas estrategias para prevenir la transmisión del VIH e incrementar el testeo para aquellos con mayor riesgo al contagio. Como parte de un ensayo controlado aleatorio (ECA) multicentrico, exploramos las actitudes y preferencias entre 272 hombres VIH-negativos que tienen sexo con hombres y mujeres transgenero VIH-negativos que utilizaron kits del auto-test para el VIH (HIVST) para testear a sus parejas. Menos de una cuarta parte de los participantes había utilizado HIVST para auto-testearse (21.7%), y solo pocos para testear a sus parejas (4.8%) antes del comienzo del estudio. El hisopo bucal fue preferido (96%) sobre una prueba con un pinchazo de sangre (69%) por la mayoría de los participantes pero estos preferirían la prueba de sangre si puedieran obtener resultados para otras enfermedades de transmisión sexual (ETS) (86%). Cinco por ciento reportó problemas con el uso de la prueba, 4% con el almacenamiento, y el 26% con la portabilidad. Noventa y tres por ciento reportó que utilizarían HIVST para testear a sus parejas en el futuro, pero solo 3% estaba dispuesto a pagar el precio actual. Los futuros esfuerzos para mejorar la adopción del HIVST deberían enfocarse en incorporar otras pruebas de ETS, en reducir el tamaño del kit y en reducir los costos.

Transgender Women's Experiences Using a Home HIV-Testing Kit for Partner-Testing.

HIV partner-testing (PT) may represent a unique and empowering HIV prevention strategy for groups that face structural and institutional barriers to HIV testing and care, including transgender women. We report on in-depth interviews (IDIs) with N = 10 transgender women who used HIV self-test kits for three months to screen potential sexual partners in a randomized controlled trial (iSUM; "I'll Show You Mine") that took place in New York City and San Juan, Puerto Rico. Participants were assigned to intervention (supplied with 10 self-test kits immediately) or control groups (received 6 test kits after 3 months). We conducted IDIs with the first N = 10 transgender women to enroll in the intervention group after three months in the study (after participants used kits with partners) to understand their experiences. Themes discussed in IDIs included: partners' reaction to HIV testing, participants' reactions to partners' test results or refusal to test, partners' own reaction to their test results, and decision-making around test use. Data were independently analyzed by two coders. Overwhelmingly, participants' experiences with PT was positive. Participants reported kits were convenient and acceptable to most partners. Transgender women felt that PT could pose additional risk for them; one woman experienced violence related to kit use. Furthermore, the availability of kits appeared to encourage participants and their partners to think about their HIV status and, in some cases, modify sexual behavior. Work suggests that HIV PT could be a viable risk-reduction strategy for transgender women.

Information and Motivation Predict HIV-Serostatus Among a Population of High-Risk Men and Transgender Women Who Have Sex with Men.

Two constructs from the information-motivation-behavioral skills model were used to predict HIV-serostatus among a sample of men and transgender women who have sex with men. Hypotheses were that lower levels of HIV knowledge and lower levels of motivation to remain HIV-negative would be associated with an increased likelihood of receiving a positive HIV test result at a study eligibility-screening session. Results of a backwards stepwise logistic regression analysis demonstrated that lower levels of HIV knowledge, lower levels of motivation to remain HIV-negative, lower levels of education, and identifying as Hispanic/Latinx were associated with greater odds of receiving a positive HIV test result. These findings are consistent with the broader HIV-prevention literature that demonstrates that information and motivation are fundamental determinants of HIV preventive behavior. This work has implications for informing the development and improvement of HIV-prevention interventions.

Use of HIV Self-Testing Kits to Screen Clients Among Transgender Female Sex Workers in New York and Puerto Rico.

Transgender female sex workers (TFSW) are highly affected by HIV, with a global prevalence of 27%. HIV self-testing (HIVST) to screen sexual partners has helped men who have sex with men and female sex workers make informed sexual decisions and avoid HIV exposure. This is the first report on TFSW's experiences screening clients using HIVST. Ten TFSW were each given ten HIVST kits and returned after 3 months to complete an online questionnaire and undergo an interview. Eight of them reported using HIVST with potential partners. Among fifty potential partners who were asked in person to test, 42 (84%) were clients. Thirty-four out of fifty (68%) accepted and 16 (32%) refused. Very few violent incidents occurred, and participants felt empowered by offering HIVST to others. Nevertheless, HIVST market cost was prohibitive for future use. HIVST use with clients could be feasible for TFSW if the cost were lowered or subsidized.

Few Aggressive or Violent Incidents are Associated with the Use of HIV Self-tests to Screen Sexual Partners Among Key Populations.

Men who have sex with men and transgender women who had multiple sexual partners in the prior 3 months participated in ISUM, a randomized, controlled trial of self- and partner-testing in New York City and San Juan, PR. Only 2% of screened participants were ineligible to enroll due to anticipating they would find it very hard to avoid or handle violence. The intervention group received free rapid HIV self-test kits. During the trial, 114 (88%) of intervention participants who were assessed at follow-up used self-tests with at least one potential partner. Only 6% of participants who asked a partner in person to test reported that at least one of their partners got physically violent, some in the context of sex work. In total, 16 (2%) partners reacted violently. Post-trial, only one participant reported finding it very hard to handle violence, and none found it very hard to avoid potential violence.

Broaching the Topic of HIV Self-testing with Potential Sexual Partners Among Men and Transgender Women Who Have Sex with Men in New York and Puerto Rico.

Men who have sex with men (MSM) and transgender women (TGW) are highly affected by HIV and need novel prevention strategies. Using HIV self-testing (HIVST) kits to screen sexual partners may represent a viable risk-reduction alternative; however, more research is needed on effective strategies for broaching HIVST with partners. In the ISUM study, 136 MSM and TGW were given ten HIVST kits for self- and partner-testing. After 3 months, they returned for a follow-up assessment; thirty participants were also selected for in-depth interviews about their experiences initiating HIVST with partners. Most found proposing HIVST to a diverse array of partners relatively easy. They employed strategies such as joint testing and integrating HIVST into larger discussions about protection and sexual health, with moderate success. Nonetheless, real or anticipated negative partner reactions were a significant barrier. Future research can inform best practices for safely and successfully broaching HIVST with sexual partners.

RESUMEN: Los hombres que tienen sexo con hombres (HSH) y las mujeres tránsgenero (MTG) están muy afectados por el VIH y necesitan estrategias innovadoras de prevención. El uso del autotest de VIH (HIVST) para testear a parejas sexuales podría ser una alternativa viable de reducir el riesgo; sin embargo, se necesitan más investigaciones sobre estrategias eficaces para abordar el tema de usar el HIVST con parejas. En el estudio ISUM, 136 HSH y MTG fueron provistos de diez HIVST para testear a sí mismo y a parejas. Después de tres meses, volvieron para una evaluación de seguimiento; treinta participantes también fueron seleccionados para una entrevista en profundidad sobres sus experiencias abordando el tema del uso del HIVST con parejas. La mayoría encontró que proponer HIVST a una gran variedad de parejas fue relativamente fácil. Emplearon estrategias como hacerse la prueba juntos y integrar HIVST en una conversación más amplia sobre la protección y la salud sexual, con leve éxito. No obstante, las reacciones negativas de parejas, ya sean reales o anticipadas, representaron una barrera importante. Las investigaciones futuras pueden informar las mejores prácticas para abordar el tema de HIVST con parejas sexuales de manera segura y exitosa.

Lessons for Rectal Microbicide Development From an Acceptability Trial of a Placebo Gel Applied Prior to Receptive Anal Intercourse.

Rectal microbicides, formulated as a gel to be applied before and/or after intercourse, are promising HIV prevention agents and are now in Phase II trials. However, both an optimal formulation and a practical delivery system are needed to ensure that the target population will use the product once efficacy is demonstrated. The precise dynamics of lubricant application by gay and bisexual men who practice anal sex and the qualities they seek in these products are underexplored. As part of a Phase I microbicide acceptability and adherence study conducted in one Puerto Rican and two continental U.S. cities, we recruited 124 young men who have sex with men (YMSM) with a history of unprotected receptive anal intercourse (RAI) and provided them with 40 rectal applicators containing a placebo gel to use prior to RAI during a 12-week period as a proxy for an eventual rectal microbicide. Ninety-five YMSM completed the trial. Their varied preferences as to product viscosity, durability, residue, and mode of application provide important lessons for the design of a product that will be satisfactory to users. Despite many reservations, the participants used the product frequently and found ways to overcome a range of obstacles. A successful rectal microbicide product may need to be presented in a range of viscosities to attract a broad client base.

Interactive Voice Response System: Data Considerations and Lessons Learned During a Rectal Microbicide Placebo Adherence Trial for Young Men Who Have Sex With Men.

BACKGROUND: Rectal microbicides, if proven effective, may aid in reducing human immunodeficiency virus (HIV) incidence; however, demonstration of efficacy and effectiveness is contingent on accurate measurement of product adherence. Delays in self-report, in particular, may affect the accuracy of behavioral data. OBJECTIVE: The aim of this study was to capitalize on mobile phone use by young men who have sex with men (YMSM), and examine the use of an interactive voice response system (IVRS) by YMSM aged 18-30 years enrolled in a multisite, 12-week microbicide safety and acceptability trial. METHODS: YMSM (N=95) enrolled across 3 sites (Boston, Pittsburgh, and San Juan) were asked to report their use of an applicator applied placebo rectal gel product during receptive anal intercourse (RAI) using the IVRS. IVRS was available in Spanish and English. After the 12-week trial, we examined whether IVRS problems were associated with YMSM's sociodemographic characteristics (eg, age, race and ethnicity, and education), sexual behavior, or recruitment site. We used a multinomial logistic regression to compare YMSM who experienced no IVRS problems (n=40) with those who reported one IVRS problem (n=25) or two or more IVRS problems (n=30). RESULTS: We recorded 1494 IVRS calls over 12 weeks. Over half of the participants (55/95; 58%) experienced challenges using the IVRS during the 12-week trial. YMSM reporting greater RAI occasions during the trial were more likely to experience one (odds ratio [OR]=1.08, 95% CI (1.02-1.14); P ≤.01) or more (OR=1.10, 95% CI (1.03-1.16); P ≤.001) IVRS challenges. Greater educational attainment was associated with multiple IVRS challenges (OR=7.08, 95% CI (1.6-31.6); P ≤.01). Participants in the Puerto Rico site were most likely to report multiple IVRS problems. CONCLUSIONS: Although IVRS was a useful data collection technology in our trial, several challenges experienced by English and Spanish speaking YMSM diminish its overall acceptability. We discuss strategies to optimize future development of IVRS data quality protocols based on lessons learned.

Acceptability of Three Novel HIV Prevention Methods Among Young Male and Transgender Female Sex Workers in Puerto Rico.

Sex workers need HIV-prevention methods they can control and incorporate easily in their work. We studied the acceptability of three methods: HIV self-test use with clients, oral pre-exposure prophylaxis (PrEP), and rectal microbicide gel. Four male and eight transgender female (TGF) sex workers in Puerto Rico completed a baseline survey with a quantitative measure of likelihood of use. From them, one male and four TGF also completed a 12-week study of rectal microbicide placebo gel use prior to receptive anal intercourse with male clients and evaluated via qualitative in-depth interviews and follow-up quantitative assessments how each method could be incorporated into their work. Most were interested in a rectal microbicide gel and able to use it covertly with clients. Challenges to using the HIV self-test with clients included the potential for both breach of confidentiality and confronting violent situations. Participants also expressed interest in oral PrEP, but raised concerns about side effects.

Rectal-specific microbicide applicator: evaluation and comparison with a vaginal applicator used rectally.

An applicator designed for rectal delivery of microbicides was tested for acceptability by 95 young men who have sex with men, who self-administered 4 mL of placebo gel prior to receptive anal intercourse over 90 days. Subsequently, 24 of the participants self-administered rectally 4 mL of tenofovir or placebo gel over 7 days using a vaginal applicator, and compared both applicators on a Likert scale of 1-10, with 10 the highest rating. Participants reported high likelihood to use either applicator in the future (mean scores 9.3 and 8.8 respectively, p = ns). Those who tested both liked the vaginal applicator significantly more than the rectal applicator (7.8 vs. 5.2, p = 0.003). Improvements in portability, conspicuousness, aesthetics, tip comfort, product assembly and packaging were suggested for both. This rectal-specific applicator was not superior to a vaginal applicator. While likelihood of future use is reportedly high, factors that decrease acceptability may erode product use over time in clinical trials. Further attention is needed to develop user-friendly, quick-acting rectal microbicide delivery systems.

Adherence to rectal gel use among mainly ethnic minority young men who have sex with men during a 3-month placebo gel trial: implications for microbicide research.

To study adherence to product use prior to a Phase I microbicide trial, we recruited young men who have sex with men (YMSM) with a history of unprotected receptive anal intercourse (RAI) and provided them with 40 rectal applicators containing a placebo gel to use prior to RAI during a 12-week period. Ninety-five YMSM completed the trial. Based on a Computer Assisted Self Interview, 83 participants had receptive anal intercourse (RAI) (Median 12 occasions) using gel on 82.4 % of occasions (SD 26.7; 0-100). Based on an interactive voice response system, 88 participants had RAI (Median 10 occasions) using gel on 87.9 % of occasions (SD 20.0; 20-100). By applicator counts the median gel use was 12. Participants showed high adherence to gel use. Those who did not use the product consistently (n = 40) adduced not having it with them (85 %), forgetting to use it (48 %), not wanting to use it (13 %), partner refusal (10 %) and gel messiness (10 %).

Pharmacokinetics of Tenofovir Alafenamide With Boosted Protease Inhibitors in Pregnant and Postpartum Women Living With HIV: Results From IMPAACT P1026s.

BACKGROUND: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV. METHODS: IMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5-9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant. RESULTS: Twenty-nine women were enrolled from the United States (median age 31 years and weight 84.5 kg during the third trimester; 48% Black, 45% Hispanic/Latina). TAF AUCtau did not significantly differ in the second [GMR 0.62 (90% CI: 0.29 to 1.34); P = 0.46] or third trimester [GMR 0.94 (90% CI: 0.63 to 1.39); P = 0.50] vs. postpartum and were comparable with historical data in nonpregnant adults. TAF was only quantifiable in 2/25 maternal delivery samples and below the limit of quantification in all cord blood and infant washout samples, likely because of the short half-life of TAF. CONCLUSION: TAF AUCtau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.

The Historic Elimination of Mother-to-Child HIV and Syphilis Transmission in Puerto Rico.

The elimination of HIV and syphilis from Puerto Rico as per metrics of the World Health Organization has been achieved despite continued HIV risk and high background prevalence. Excellence in antenatal services and screening, deployment of antiretroviral and penicillin syphilis therapies, and proper follow-through with mothers and infants has yielded success even as control of infection overall remains elusive. We highlight the context of this achievement in our editorial to accompany the article: "Elimination of the Perinatal Transmission of HIV and Syphilis in Puerto Rico and Sustained Success since 2007: Convergence of Science, Women-Centered Care, and Policy".

Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV.

OBJECTIVE: To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. DESIGN: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States. METHODS: Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons. RESULTS: A total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [n = 12, P = 0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 - 0.68] and 56% lower in the third trimester (n = 18, P < 0.0001, GMR = 0.44, 90% CI 0.36 - 0.54), whereas cobicistat AUC0--24 was 50% lower in the second trimester (n = 12, P = 0.0024, GMR = 0.50, 90% CI 0.36-0.69) and 56% lower in the third trimester (n = 18, P < 0.0001, GMR = 0.44, 90% CI 0.35-0.55). Placental transfer of darunavir and cobicistat was limited. CONCLUSION: Standard darunavir/cobicistat dosing during pregnancy results in significantly lower exposure during pregnancy, which may increase the risk of virologic failure and perinatal transmission.

Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV.

OBJECTIVE: To evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics. DESIGN: Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery, and infant washout. METHODS: Pregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using liquid chromatography/mass spectrometry. Comparisons between pregnancy and postpartum were made using geometric mean ratios (90% confidence intervals) and Wilcoxon signed-rank tests. RESULTS: Thirty-one pregnant women receiving TAF 10 mg with cobicistat-boosting and 27 women receiving TAF 25 mg without boosting were enrolled. TAF exposures did not significantly differ between pregnancy and postpartum when administered as 10 mg with cobicistat. Antepartum TAF exposures with the 25 mg dose were 33-43% lower in comparison with postpartum, but comparable with those measured in nonpregnant adults. TAF was below the lower limit of quantitation in 43 of 44 cord blood, 41 of 45 maternal blood at delivery, and all infant washout samples. CONCLUSION: TAF exposures were comparable or higher than those measured in nonpregnant adults during pregnancy and postpartum. These findings provide reassurance on adequate TAF exposures during pregnancy, and support efforts to expand the use of TAF in pregnant women with HIV.

Text Messaging and Disaster Preparedness Aids Engagement, Re-Engagement, Retention, and Communication Among Puerto Rican Participants in a Human Immunodeficiency Virus (HIV) Self-Testing Study After Hurricanes Irma and Maria.

OBJECTIVE: Hurricanes can interrupt communication, exacerbate attrition, and disrupt participant engagement in research. We used text messaging and disaster preparedness protocols to re-establish communication, re-engage participants, and ensure retention in a human immunodeficiency virus (HIV) self-test study. METHODS: Participants were given HIV home test kits to test themselves and/or their non-monogamous sexual partners before intercourse. A daily text message-based short message service computer-assisted self-interview (SMS-CASI) tool reminded them to report 3 variables: (1) anal sex without a condom, (2) knowledge of partners' testing history, and (3) proof of partners' testing history. A disaster preparedness protocol was put in place for hurricanes in Puerto Rico. We analyzed 6315 messages from participants (N = 12) active at the time of Hurricanes Irma and Maria. Disaster preparedness narratives were assessed. RESULTS: All participants were able to communicate sexual behavior and HIV testing via SMS-CASI within 30 days following María. Some participants (n = 5, 42%) also communicated questions. Re-engagement within 30 days after the hurricane was 100% (second week/89%, third week/100%). Participant re-engagement ranged from 0-16 days (average = 6.4 days). Retention was 100%. CONCLUSIONS: Daily SMS-CASI and disaster preparedness protocols helped participant engagement and communication after 2 hurricanes. SMS-CASI responses indicated high participant re-engagement, retention, and well-being.

Safety and Immunogenicity of Different Formulations of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults from Puerto Rico: Final Results after 3 Years of Follow-Up from a Randomized, Placebo-Controlled Phase I Study.

Four formulations of an investigational tetravalent dengue purified inactivated vaccine, administered as two doses one month (M) apart, were previously shown to be immunogenic and well-tolerated up to M13 of the phase I study NCT01702857. Here, we report results of the follow-up from M14 to year (Y) 3. One hundred healthy Puerto Rican adults, predominantly dengue virus (DENV)-primed, were randomized 1:1:1:1:1 to receive placebo or vaccine formulations: 1 µg/serotype/dose adjuvanted with aluminum, AS01E or AS03B, or aluminum-adjuvanted 4 µg/serotype/dose. No serious adverse events occurred. Two medically-attended potential immune-mediated disease cases, vaccination unrelated, were reported (groups 1 µg+Alum and 1 µg+AS03B). Of 14 instances of suspected dengue, none were laboratory confirmed. Geometric mean neutralizing antibody titers against DENV 1-4 waned from M14, but remained above pre-vaccination levels for DENV 1-3, with the highest values for group 1 µg+AS03B: 1220.1, 920.5, 819.4, and 940.5 (Y2), and 1329.3, 1169.2, 1219.8, and 718.9 (Y3). All formulations appeared to be safe and immunogenic during the 3-year follow-up.