Brain computed tomography perfusion analysis in HIV-seropositive adults with and without neurocognitive impairment in Nigeria: outcomes and challenges of a pilot study.

Introduction: the significance of cerebrovascular disease in HIV-associated neurocognitive disorder (HAND) in a homogeneous black population has not yet been determined. This incident case-control study used CT perfusion imaging to quantify and compare regional cerebral blood flow parameters in neuro-cognitively impaired and unimpaired HIV+ participants of the Ibadan Cohort on Neuro AIDS (ICON) in Nigeria. Methods: this was an incident case-control study consisting of twenty-seven HIV+ adults, classified based on Frascati criteria into neurocognitive impaired (n=18) and unimpaired (n=9) groups, who had brain computed tomographic perfusion (CTP) with a 64-slice Toshiba T scanner. The standard deviation (SD) of regional mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) values were calculated for bilateral basal ganglia (BG), frontal, parietal, temporal, and occipital regions from CT perfusion maps. The regional mean values and variability (SD) in the CTP measures were compared in the groups using an independent student t-test. Results: differentially higher variability in the bilateral CBF measures in the parietal (right; OR = 1.14, x̄ =5.61, p=0.041, CI=0.27-11.35/left; OR = 1.16, x̄=7.01, p=0.03, CI=5.6-13.47) and time to peak (TTP) measures in the basal ganglia (right; OR = 3.78, x̄=0.88, p=0.032, CI=0.081-1.67/left; OR = 2.44, x̄=1.48, p=0.020, CI=0.26-2.71) and occipital (right; OR = 2.18, x̄=1.32, p=0.018, CI=0.25-2.38/left; OR = 1.93, x̄=1.08, p=0.034, CI=0.086-2.06) regions were observed in the cognitively impaired group compared to the unimpaired group. Conclusion: the study evidence suggests that alterations in cerebral perfusion implicated in HIV-associated neurocognitive disorder may be possibly demonstrated using CTP, a readily available resource in most African countries saddled with the highest burden of HIV.

Successful Implementation Strategies in iCARE Nigeria-A Pilot Intervention with Text Message Reminders and Peer Navigation for Youth Living with HIV.

To address poor outcomes among adolescents and young adults living with HIV (AYA-HIV), iCARE Nigeria successfully piloted two-way text message antiretroviral therapy (ART) reminders together with peer navigation. Study participants had significant improvement in ART adherence and viral suppression at 48 weeks. Understanding facto of this intervention. We used explanatory, mixed methods to assess implementation outcomes (feasibility, acceptability, and adoption) and identify implementation strategies used or adapted to promote intervention success. Quantitative data included participant surveys, program records, and back-end mHealth data, and were summarized using descriptive statistics. Qualitative data were collected from key informants and focus group discussions with program staff and summarized using directed content analysis. iCARE Nigeria was feasible as evidenced by ease of recruitment, high retention of patients and peer navigators (PN), and successful deployment of initial text message reminders (99.9%). Most participants (95%) and PN (90%) found text message reminders were not bothersome or intrusive. Implementation strategies employed to facilitate intervention success included: (1) selecting, training, supervising, and matching of PN to patients; (2) tailoring frequency (daily to weekly) and mode of communication between PN and patients according to patient need; (3) routine screening for adherence challenges; (4) changing phone airtime stipends from monthly to weekly in response to rapid depletion; and (5) conducting telecommunication needs assessments, to identify and troubleshoot implementation barriers (issues with mobile devices, power availability). iCARE Nigeria was feasible and acceptable with high adoption by stakeholders. The implementation strategies identified here can be tailored for intervention scale-up in similar environments to promote ART adherence for AYA-HIV.

A randomized stepped wedge trial of an intensive combination approach to roll back the HIV epidemic in Nigerian adolescents: iCARE Nigeria treatment support protocol.

BACKGROUND: Nigeria is one of six countries with half the global burden of youth living with HIV. Interventions to date have been inadequate as AIDS-related deaths in Nigeria's youth have remained unchanged in recent years. The iCARE Nigeria HIV treatment support intervention, a combination of peer navigation and SMS text message medication reminders to promote viral suppression, demonstrated initial efficacy and feasibility in a pilot trial among youth living with HIV in Nigeria. This paper describes the study protocol for the large-scale trial of the intervention. METHODS: The iCARE Nigeria-Treatment study is a randomized stepped wedge trial of a combination (peer navigation and text message reminder) intervention, delivered to youth over a period of 48 weeks to promote viral suppression. Youth receiving HIV treatment at six clinical sites in the North Central and South Western regions of Nigeria were recruited for participation. Eligibility criteria included registration as a patient at participating clinics, aged 15-24 years, on antiretroviral therapy for at least three months, ability to understand and read English, Hausa, Pidgin English, or Yoruba, and intent to remain a patient at the study site during the study period. The six clinic sites were divided into three clusters and randomized to a sequence of control and intervention periods for comparison. The primary outcome is plasma HIV-1 viral load suppression, defined as viral load ≤ 200 copies/mL, in the intervention period versus the control period at 48 weeks of intervention. DISCUSSION: Evidence-based interventions to promote viral load suppression among youth in Nigeria are needed. This study will determine efficacy of a combination intervention (peer navigation and text message reminder) and collect data on potential implementation barriers and facilitators to inform scale-up if efficacy is confirmed. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04950153, retrospectively registered July 6, 2021, https://clinicaltrials.gov/.

Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus.

BACKGROUND: Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system. METHODS: A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48. RESULTS: Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10). CONCLUSIONS: This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.

The importance of methods for site performance evaluation in REPRIEVE, a longitudinal, global, multicenter trial.

BACKGROUND: REPRIEVE, the Randomized Trial to Prevent Vascular Events in HIV, is a multicenter, primary prevention trial evaluating whether a statin can prevent major cardiovascular events in people with HIV. REPRIEVE is conducted at >100 clinical research sites (CRSs) globally. Detailed, comprehensive, and novel methods for evaluating and communicating CRS performance are required to ensure trial integrity and data quality. In this analysis we describe a comprehensive multidimensional methodology for evaluating CRS performance. METHODS: The REPRIEVE Data Coordinating and Clinical Coordinating Centers developed a robust system for evaluation of and communication with CRSs, designed to identify potential issues and obstacles to performance, provide real-time technical support, and make recommendations for process improvements to facilitate efficient trial execution. We describe these systems and evaluate their impact on participant retention, data management, and specimen management from 2019 to 2022, corresponding to the period from end of recruitment to present. This evaluation was based on pre-defined metrics, regular reviews, and bidirectional communication. RESULTS: Participant retention, data management, and specimen management all remained steady over the three-year period, although metrics varied by country of enrollment. Targeted messaging relating to certain performance metrics was effective. CONCLUSION: Site performance is vital to ensure trial integrity and achievement of key trial goals. This analysis demonstrates that utilization of a comprehensive approach allows for a thorough evaluation of CRS performance, facilitates data and specimen management, and enhances participant retention. Our approach may serve as a guidepost for maximizing future large-scale clinical trials' operational success and scientific rigor. CLINICALTRIALS: gov Identifier: NCT02344290.

Comparison of efavirenz levels in blood and hair with pharmacy refills as measures of adherence and predictors of viral suppression among people living with HIV in Nigeria.

BACKGROUND: Strategies to support adherence are constrained by the lack of tools to objectively monitor medication intake in low-resource settings. Pharmacologic measures are objective, but pharmacy refill data is more accessible and cost-efficient. This study compared short-term and long-term efavirenz (EFV) drug levels with pharmacy refill adherence data (PRA) and evaluated their ability to predict viral suppression among people living with HIV in Nigeria. METHODS: Paired hair and dried blood spot (DBS) samples were obtained from 91 adults living with HIV receiving 600 mg EFV-based antiretroviral therapy (ART) and EFV concentrations were measured via validated methods using liquid-chromatography-mass-spectrometry. PRA was estimated from pharmacy records, based on the number of days a patient collected medication before or after the scheduled pick-up date. PRA was categorized into ≤ 74%, 75-94% and ≥ 95%, defined as poor, medium and high adherence, respectively. HIV viral loads closest to the hair sampling time (within 6 months) were also abstracted. Receiver Operating Characteristics (ROC) curve analyses compared the ability of adherence metrics to predict viral suppression. RESULTS: Based on PRA, 81% of participants had high adherence while 11% and 8% had medium and poor adherence, respectively. The median (IQR) EFV concentrations were 6.85 ng/mg (4.56-10.93) for hair and 1495.6 ng/ml (1050.7-2365.8) for DBS. Of the three measures of adherence, hair EFV concentration had the highest Area Under Curve (AUC) to predict viral suppression. Correlations between EFV concentrations in DBS and hair with PRA were positive (r = 0.12, P = 0.27 and r = 0.21, P = 0.05, respectively) but not strong. CONCLUSIONS: EFV concentrations in hair were the strongest predictor of viral suppression and only weakly correlated with pharmacy refill adherence data in Nigeria. This study suggests that resource-limited settings may benefit from objective adherence metrics to monitor and support adherence.

Post-migration HIV acquisition among african immigrants in the U.S.

BACKGROUND: African immigrants in the U.S. are more likely to have a late HIV diagnosis than U.S.-born people, potentially leading to onward transmission. We sought to determine the proportion of African-born people living with HIV (APLWH) who (1) had tested HIV negative prior to diagnosis, and (2) likely acquired HIV in the U.S. METHODS: We interviewed APLWH from 2014 to 2017 and estimated the proportion with post-migration HIV acquisition based on clinical data, HIV testing history, immigration date, and behavioral data. RESULTS: Of 179 participants, 113 (63%) were women. Less than half (44%) reported a negative HIV test prior to diagnosis. Among 142 (79%) participants with sufficient data to evaluate post-migration HIV acquisition, we estimate that 29% acquired HIV post-migration. Most APLWH acquire HIV prior to immigration. DISCUSSION: Approximately one-quarter of APLWH acquire HIV post-migration and HIV testing is infrequent, highlighting the need for prevention efforts for African immigrants in the U.S.

Evaluation of the iCARE Nigeria Pilot Intervention Using Social Media and Peer Navigation to Promote HIV Testing and Linkage to Care Among High-Risk Young Men: A Nonrandomized Controlled Trial.

Importance: Nigeria has the fourth-largest HIV epidemic globally, yet high levels of social stigma inhibit HIV testing among Nigerian youths and young men who have sex with men (MSM). Objective: To report pilot data from iCARE Nigeria (Intensive Combination Approach to Roll Back the Epidemic in Nigerian Adolescents), a combination intervention using social media and peer navigation to promote HIV testing and linkage to care among high-risk youths and young men (hereinafter referred to as young men), including predominantly young MSM. Design, Setting, and Participants: This nonrandomized controlled study assessed an organizational and community-level 12-month, preintervention-postintervention pilot trial of a combination intervention designed to increase HIV testing uptake, increase the rate of identified seropositive cases, and improve linkage to care among young men, including MSM, using social media outreach and peer navigation. Data were collected from June 1, 2019, to May 30, 2020. Participants were young men aged 15 to 24 years in the city of Ibadan, Nigeria, and surrounding areas. Frequencies and percentages were examined, and a Fisher exact test was used to evaluate outcomes compared with historical surveillance data. Linkage to care was defined as 2 clinic visits, including HIV confirmation, within 2 months of a positive rapid test result. Intervention: Four peer navigators conducted social media outreach promoting sexual health and guiding individuals to HIV counseling and rapid testing in clinical, community, or home-based settings. Main Outcomes and Measures: Primary outcomes included the number of young men tested for HIV at university-based iCARE catchment clinics or by iCARE peer navigators in the community, the postintervention HIV seroprevalence of these groups, and linkage to care of participants diagnosed with HIV infection. Results: A total of 339 participants underwent testing for HIV (mean [SD] age, 21.7 [1.9] years), with 283 (83.5%) referred through social media. The main referral sources for social media were WhatsApp (124 [43.8%]), Facebook (101 [35.7%]), and Grindr (57 [20.1%]). Regarding testing location, participants chose home (134 [39.5%]), community-based (202 [59.6%]), or clinic (3 [0.9%]) settings. Eighty-six participants reported no prior HIV testing. Thirty-six participants (10.6%) were confirmed as HIV seropositive; among those, 18 (50.0%) reported negative test results within the past year, and 31 (86.1%) were linked to care. In two 6-month follow-up periods, the intervention increased HIV testing by 42% and 31%, respectively, and seroprevalence increased compared with historical trends with odds ratios of 3.37 (95% CI, 1.43-8.02; P = .002) and 2.74 (95% CI, 1.10-7.11; P = .02), respectively. Conclusions and Relevance: These findings suggest that use of iCARE Nigeria was associated with increased HIV testing and linkage to care in a high-risk, difficult-to-reach population, making it a promising combination intervention for young MSM. Trial Registration: isrctn.org Identifier: ISRCTN94590823.

No difference in anti-spike antibody and surrogate viral neutralization following SARS-CoV-2 booster vaccination in persons with HIV compared to controls (CO-HIV Study).

Background: Understanding the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination will enable accurate counseling and inform evolving vaccination strategies. Little is known about antibody response following booster vaccination in people living with HIV (PLWH). Methods: We enrolled SARS-CoV-2 vaccinated PLWH and controls without HIV in similar proportions based on age and comorbidities. Participants completed surveys on prior SARS-CoV-2 infection, vaccination, and comorbidities, and provided self-collected dried blood spots (DBS). Quantitative anti-spike IgG and surrogate viral neutralization assays targeted wild-type (WT), Delta, and Omicron variants. We also measured quantitative anti-nucleocapsid IgG. The analysis population had received full SARS-CoV-2 vaccination plus one booster dose. Bivariate analyses for continuous outcomes utilized Wilcoxon tests and multivariate analysis used linear models. Results: The analysis population comprised 140 PLWH and 75 controls with median age 58 and 55 years, males 95% and 43%, and DBS collection on 112 and 109 days after the last booster dose, respectively. Median CD4 count among PLWH was 760 cells/mm3 and 91% had an undetectable HIV-1 viral load. Considering WT, Delta, and Omicron variants, there was no significant difference in mean quantitative anti-spike IgG between PLWH (3.3, 2.9, 1.8) and controls (3.3, 2.9, 1.8), respectively (p-values=0. 771, 0.920, 0.708). Surrogate viral neutralization responses were similar in PLWH (1.0, 0.9, and 0.4) and controls (1.0, 0.9, 0.5), respectively (p-values=0.594, 0.436, 0.706). Conclusions: PLWH whose CD4 counts are well preserved and persons without HIV have similar anti-spike IgG antibody levels and viral neutralization responses after a single SARS-CoV-2 booster vaccination.

Adaptation of evidence-based approaches to promote HIV testing and treatment engagement among high-risk Nigerian youth.

BACKGROUND: Nigeria has the second highest number of people living with HIV (PLWH) globally, and evidence-based approaches are needed to achieve national goals to identify, treat, and reduce new infections. Youth between the ages of 15-24, including young men who have sex with men (YMSM), are disproportionately impacted by the Nigerian HIV epidemic. The purpose of this study was to inform adaptation of evidence-based peer navigation and mHealth approaches (social media outreach to promote HIV testing; short messaging service text message reminders to promote HIV treatment engagement) to the local context within iCARE Nigeria, a multi-phase study designed to investigate combination interventions to promote HIV testing and care engagement among youth in Nigeria. METHODS: To elicit expert and community perspectives, a local group of advisors from academia, community, and governmental sectors provided feedback on intervention adaptation, which then informed a series of focus groups with stakeholders in Ibadan, Nigeria. Focus group data were collected over a period of three days in December of 2018. Participants in focus groups included YMSM and HIV-positive youth in care ages 16-24, and HIV service providers from local AIDS service organizations (ASO). Groups were stratified by HIV serostatus, gender, and stakeholder type. Focus group sessions were conducted using a semi-structured interview guide, audio-recorded, transcribed verbatim, and analyzed using a content analysis approach. RESULTS: Local experts recommended intervention adaptations specific to the status of peer navigators as volunteers, peer characteristics (slightly older age, high maturity level, HIV/YMSM status), and intervention characteristics and resources (low navigator to peer ratio; flexible matching by demographic and social characteristics; social media platforms and content). Five focus group discussions with stakeholders, including 27 participants were conducted to elicit feedback on these and other potential adaptations. Youth participants (n = 21) were mean age 20 years (range = 16-24); 76% HIV-positive, 76% men and 48% MSM. Service providers (n = 6) represented both HIV prevention and care services. Participants across stratified subgroups reported largely positive perceptions and high perceived acceptability of both mHealth and peer navigation strategies, and echoed the recommendations of the advisory group for volunteer-based navigators to promote altruism, with a low navigator-peer ratio (1:5). Participants emphasized the need to incorporate minimal mobile data use strategies and popular social media platforms among YMSM (e.g., Facebook, Grindr) for widespread access and reach of the interventions. CONCLUSIONS: In Ibadan, Nigeria, stakeholders support the adaptation of combined mHealth and peer navigation strategies to promote HIV testing and care engagement among high-risk youth. Recommended adaptations for the local context reflect concerns about the feasibility and sustainability of the intervention and are expected to improve accessibility and acceptability.

Effect of Text Messaging Plus Peer Navigation on Viral Suppression Among Youth With HIV in the iCARE Nigeria Pilot Study.

BACKGROUND: Consistent with the global trend, youth with HIV (YWH) in Nigeria have high rates of viral nonsuppression. Hence, novel interventions are needed. SETTING: Infectious Diseases Institute, College of Medicine, University of Ibadan, Nigeria. METHODS: In a single-arm trial, participants aged 15-24 years received 48 weeks of a combination intervention, comprising daily 2-way text message medication reminders plus peer navigation. The primary outcome measure was viral suppression less than 200 copies/mL. The secondary outcome measures included self-reported adherence on a visual analog scale and medication possession ratio, each dichotomized as ≥90% (good) or <90% (poor) adherence. The outcomes were analyzed using McNemar test. Retention in care, intervention feasibility and acceptability, and participants' satisfaction were also assessed. RESULTS: Forty YWH (50% male participants) were enrolled: mean age 19.9 years (SD = 2.5), 55% perinatally infected, and 35% virologically suppressed at baseline. Compared with baseline, the odds of virologic suppression was higher at 24 weeks (odds ratio = 14.00, P < 0.001) and 48 weeks (odds ratio = 6.00, P = 0.013). Self-reported adherence (≥90%) increased from baseline at 24 weeks (63%, P = 0.008) and 48 weeks (68%, P = 0.031). Medication possession ratio ≥90% increased at weeks 24 and 48 (85% and 80%, respectively), achieving statistical significance at 24 weeks alone (P = 0.022). Retention in care at 48 weeks was 87.5%. All (37/37) participants at week 48 were fully or mostly satisfied with the intervention. CONCLUSION: Daily 2-way text message reminders plus peer navigation is a promising combination intervention to improve viral suppression among YWH in Nigeria.

Associations between efavirenz concentrations, pharmacogenetics and neurocognitive performance in people living with HIV in Nigeria.

OBJECTIVE: Efavirenz (EFV) use is associated with neuropsychiatric side effects, which may include poor neurocognitive performance. We evaluated single nucleotide polymorphisms in genes that contribute to EFV pharmacokinetics and examined them in association with EFV concentrations in plasma and hair, as well as neurocognitive performance. DESIGN: Cross-sectional study in which adults with HIV receiving 600-mg EFV for at least 2 months were recruited and paired hair and dried blood spots (DBS) samples collected. METHODS: Participants (N = 93, 70.3% female) were genotyped for seven single nucleotide polymorphisms in CYP2B6, NRII3 and ABCB1 using DBS. EFV was quantified in DBS and hair using validated liquid-chromatography-tandem-mass-spectrometry methods, with plasma EFV concentrations derived from DBS levels. Participants were also administered a neurocognitive battery of 10 tests (seven domains) that assessed total neurocognitive functioning. RESULTS: Strong correlation (r = 0.66, P < 0.001) was observed between plasma and hair EFV concentrations. The median (interquartile range) hair EFV concentration was 6.85 ng/mg (4.56-10.93). CYP2B6 516G>T, (P < 0.001) and CYP2B6 983T>C (P = 0.001) were each associated with hair EFV concentrations. Similarly, 516G>T (P < 0.001) and 983T>C (P = 0.009) were significantly associated with plasma EFV concentration. No other genetic associations were observed. Contrary to other studies, total neurocognitive performance was significantly associated with plasma EFV concentrations (r = 0.23, P = 0.043) and 983T>C genotype (r = 0.38, P < 0.0005). CONCLUSION: This study demonstrated approximately three-fold and two-fold higher EFV plasma and hair concentrations, respectively, among CYP2B6 516TT compared with 516GG. Higher EFV concentrations were associated with better neurocognitive performance, requiring further study to elucidate the relationships between adherence, adverse effects and outcomes.

Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives.

OBJECTIVE: In AIDS Clinical Trials Group study A5316, efavirenz lowered plasma concentrations of etonogestrel and ethinyl estradiol, given as a vaginal ring, while atazanavir/ritonavir increased etonogestrel and lowered ethinyl estradiol concentrations. We characterized the pharmacogenetics of these interactions. METHODS: In A5316, women with HIV enrolled into control (no antiretrovirals), efavirenz [600 mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)], and atazanavir/ritonavir (300/100 mg daily with NRTIs) groups. On day 0, a vaginal ring was inserted, releasing etonogestrel/ethinyl estradiol 120/15 µg/day. Intensive plasma sampling for antiretrovirals was obtained on days 0 and 21, and single samples for etonogestrel and ethinyl estradiol on days 7, 14, and 21. Seventeen genetic polymorphisms were analyzed. RESULTS: The 72 participants in this analysis included 25, 24 and 23 in the control, efavirenz, and atazanavir/ritonavir groups, respectively. At day 21 in the efavirenz group, CYP2B6 genotype was associated with increased plasma efavirenz exposure (P = 3.2 × 10), decreased plasma concentrations of etonogestrel (P = 1.7 × 10), and decreased ethinyl estradiol (P = 6.7 × 10). Compared to controls, efavirenz reduced median etonogestrel concentrations by at least 93% in CYP2B6 slow metabolizers versus approximately 75% in normal and intermediate metabolizers. Efavirenz reduced median ethinyl estradiol concentrations by 75% in CYP2B6 slow metabolizers versus approximately 41% in normal and intermediate metabolizers. CONCLUSION: CYP2B6 slow metabolizer genotype worsens the pharmacokinetic interaction of efavirenz with hormonal contraceptives administered by vaginal ring. Efavirenz dose reduction in CYP2B6 slow metabolizers may reduce, but will likely not eliminate, this interaction.

Baseline 10-Year Cardiovascular Risk Scores Predict Cognitive Function in Older Persons, and Particularly Women, Living With Human Immunodeficiency Virus Infection.

BACKGROUND: Cardiovascular disease (CVD) and associated comorbidities increase the risk of cognitive impairment in persons living with human immunodeficiency virus (PLWH). Given the potential composite effect of multiple cardiovascular risk factors on cognition, we examined the ability of the Atherosclerotic Cardiovascular Disease (ASCVD) risk score and the Framingham Heart Study Global CVD risk score (FRS) to predict future cognitive function in older PLWH. METHODS: We constructed linear regression models evaluating the association between baseline 10-year cardiovascular risk scores and cognitive function (measured by a summary z-score, the NPZ-4) at a year 4 follow-up visit. RESULTS: Among 988 participants (mean age, 52 years; 20% women), mean 10-year ASCVD risk score at entry into the cohort was 6.8% (standard deviation [SD], 7.1%) and FRS was 13.1% (SD, 10.7%). In models adjusted only for cognitive function at entry, the ASCVD risk score significantly predicted year 4 NPZ-4 in the entire cohort and after stratification by sex (for every 1% higher ASCVD risk, year 4 NPZ-4 was lower by 0.84 [SD, 0.28] overall, P = .003; lower by 2.17 [SD, 0.67] in women, P = .001; lower by 0.78 [SD, 0.32] in men, P = .016). A similar relationship was observed between FRS and year 4 NPZ-4. In multivariable models, higher 10-year ASCVD risk and FRS predicted lower NPZ-4 in women. CONCLUSIONS: Baseline 10-year ASCVD risk and FRS predicted future cognitive function in older PLWH with well-controlled infection. Cardiovascular risk scores may help to identify PLWH, especially women, who are at risk for worse cognition over time.

Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study.

BACKGROUND: Drug-drug interactions between orally administered antiretroviral therapy (ART) and hormones released from an intravaginal ring are not known. We hypothesised that ART containing either efavirenz or ritonavir-boosted atazanavir would alter plasma concentrations of vaginally administered etonogestrel and ethinylestradiol but that ART concentrations would be unchanged during use of an intravaginal ring. METHODS: We did a parallel, three-group, pharmacokinetic evaluation at HIV clinics in Asia (two sites), South America (five), sub-Saharan Africa (three), and the USA (11) between Dec 30, 2014, and Sept 12, 2016. We enrolled women with HIV who were either ART-naive (control group; n=25), receiving efavirenz-based ART (n=25), or receiving atazanavir-ritonavir-based ART (n=24). Women receiving ART were required to be on the same regimen for at least 30 days, with 400 copies or less per mL of plasma HIV-1 RNA; women not receiving ART had CD4 counts of 350 cells per µL or less. We excluded participants who had a bilateral oophorectomy or conditions that were contraindicated in the intravaginal ring product labelling. An intravaginal ring releasing etonogestrel and ethinylestradiol was inserted at entry (day 0). Single plasma samples for hormone concentrations were collected on days 7, 14, and 21 after intravaginal ring insertion. The primary outcome was the plasma concentration of etonogestrel and ethinylestradiol on day 21. Etonogestrel and ethinylestradiol concentrations were compared between each ART group and the control group by geometric mean ratio (GMR) with 90% CIs and Wilcoxon rank-sum test. As secondary outcomes, efavirenz or ritonavir-boosted atazanavir concentrations were assessed by 8-h intensive pharmacokinetic sampling at entry before intravaginal ring insertion and before intravaginal ring removal on day 21. Antiretroviral areas under the concentration-time curve (AUC0-8 h) were compared before and after intravaginal ring insertion by GMR (90% CI) and Wilcoxon signed-rank test. This study is registered with ClinicalTrials.gov, number NCT01903031. FINDINGS: Between Dec 30, 2014, and Sept 12, 2016, we enrolled 84 participants in the study; ten participants were excluded from the primary hormone analysis. 74 participants met the primary endpoint: 25 in the control group, 25 in the efavirenz group, and 24 in the atazanavir group. On day 21 of intravaginal ring use, participants receiving efavirenz had 79% lower etonogestrel (GMR 0·21, 90% CI 0·16-0·28; p<0·0001) and 59% lower ethinylestradiol (0·41, 0·32-0·52; p<0·0001) concentrations compared with the control group. By contrast, participants receiving ritonavir-boosted atazanavir had 71% higher etonogestrel (1·71, 1·37-2·14; p<0·0001), yet 38% lower ethinylestradiol (0·62, 0·49-0·79; p=0·0037) compared with the control group. The AUC0-8 h of efavirenz or atazanavir did not differ between the groups. INTERPRETATION: Hormone exposure was significantly lower when an intravaginal ring contraceptive was combined with efavirenz-based ART. Further studies designed to examine pharmacodynamic endpoints, such as ovulation, when intravaginal ring hormones are combined with efavirenz are warranted. FUNDING: National Institutes of Health, through the AIDS Clinical Trials Group and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

HIV stigma and viral load among African-American women receiving treatment for HIV.

OBJECTIVE: African-American women are more likely than other women in the United States to experience poor HIV-related health; HIV stigma may contribute to these outcomes. This study assessed the relationship between HIV stigma and viral load, over time, among a sample of African-American women receiving treatment for HIV, and explored social support and depressive symptoms as mediators. DESIGN: Secondary analysis of longitudinal data. METHODS: Data came from a randomized trial of an intervention to reduce HIV stigma among African-American women in HIV care in Chicago, Illinois and Birmingham, Alabama. Sociodemographic and psychosocial data were collected at up to six study visits over 14 months. Viral loads were extracted from medical records during the study period. Generalized linear mixed effects models were used to estimate associations among overall, internalized, and enacted HIV stigma and viral load over time. Mediation analyses were used to estimate indirect effects via social support and depressive symptoms. RESULTS: Data from 234 women were analyzed. Overall HIV stigma was significantly associated with subsequent viral load (adjusted ß = 0.24, P = 0.005). Both between-subject (adjusted ß = 0.74, P < 0.001) and within-subject (adjusted ß = 0.34, P = 0.005) differences in enacted stigma were associated with viral load. Neither social support nor depressive symptoms were statistically significant mediators. CONCLUSION: Ongoing experiences of HIV stigmatization may contribute to increased viral load among African-American women in primary HIV care. Interventions should aim to alleviate the consequences of stigma experienced by patients and prevent future stigmatization.

Comparable viral decay with initial dolutegravir plus lamivudine versus dolutegravir-based triple therapy.

OBJECTIVES: To expand understanding of the virological potency of initial dolutegravir plus lamivudine dual therapy (dolutegravir/lamivudine), we compared the viral decay seen in the pilot ACTG A5353 study with the decay observed with dolutegravir plus two NRTIs in the SPRING-1 and SINGLE studies, while also exploring the impact of baseline viral load (VL). METHODS: Change in VL from baseline was calculated for timepoints shared by A5353 (n = 120, including 37 participants with pretreatment VL >100000 copies/mL), SPRING-1 (n = 51) and SINGLE (n = 417). The 95% CIs of change from baseline were determined for each observed week, using the mean log10-transformed VL, and compared between the dolutegravir/lamivudine and triple therapy groups using the Wilcoxon Rank Sum test for non-inferiority (δ = 0.5). To assess the impact of baseline VL on viral decay, we examined a bi-exponential non-linear mixed-effect model. RESULTS: The mean VL change from baseline to week 24 was -2.9 log10 copies/mL for dolutegravir/lamivudine versus -3.0 log10 copies/mL for dolutegravir-based three-drug therapy (P < 0.001). In the decay model, baseline VL >100000 copies/mL was associated with a slower initial decay rate (d1). A faster initial decay rate was seen with dolutegravir/lamivudine, which was partially offset when baseline VL was >100000 copies/mL as indicated by a significant interaction between baseline VL and drug therapy group. The secondary decay rate (d2) was not significantly different from zero, with no significant associations. CONCLUSIONS: Viral decay with dolutegravir/lamivudine was comparable to viral decay with dolutegravir-based triple therapy, even in individuals with higher pretreatment VL (>100000 copies/mL).

Willingness to Donate Hair Samples for Research Among People Living with HIV/AIDS Attending a Tertiary Health Facility in Ibadan, Nigeria.

The use of hair samples in biomedical research is a rapidly growing field. High acceptability rates for hair collection have been demonstrated in multiple settings. Each setting may have unique issues and, to our knowledge, no previous study has assessed the acceptability of hair sampling for HIV-related research in Nigeria. This study aimed to assess the willingness to donate hair for research among people living with HIV (PLWH). A cross-sectional study was conducted among 381 PLWH in a tertiary institution in Southwest Nigeria, using convenience sampling. An interviewer-administered questionnaire was used to collect data from consenting participants, including a question on willingness to donate hair for research. The mean age of respondents was 42.1 ± 10.5 years and more than three-quarters of the respondents were females. Two hundred and eighty-eight (75.8%) respondents had at least a tertiary education. Only 51.4% of the respondents were willing to donate their hair for research. Possible sample diversion for rituals was the major (60.5%) reason cited for unwillingness to donate hair. In multivariate analysis, respondents with primary education or less exhibited a trend toward being more willing to donate hair than those with secondary education or more (p = .091). Muslims were 1.7 times more willing to donate hair than Christians even after adjusting for other demographic covariates (95% confidence interval: 1.11-2.72); p = .016. There is a moderate willingness to donate hair for research among our population of PLWH in Nigeria. These results underscore the importance of cultural sensitivity and community education when introducing innovative HIV research techniques to new settings.

No Significant Changes to Residual Viremia After Switch to Dolutegravir and Lamivudine in a Randomized Trial.

In the ASPIRE trial, antiretroviral therapy (ART) switch to dolutegravir plus lamivudine (DTG+3TC) was comparable to 3-drug ART in maintaining viral suppression by standard viral load assays. We used an ultrasensitive assay to assess whether this switch led to increased residual viremia. At entry, levels of residual viremia did not differ significantly between arms (DTG+3TC vs 3-drug ART: mean, 5.0 vs 4.2 HIV-1 RNA copies/mL; P = .64). After randomization, no significant between-group differences were found at either week 24 or 48. These results show no evidence for increased viral replication on DTG+3TC and support its further investigation as a dual ART strategy.

Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353.

BACKGROUND: The AIDS Clinical Trials Group study A5353 demonstrated the efficacy and safety of dolutegravir and lamivudine for initial treatment of HIV-1 infection at week 24 in individuals with HIV-1 RNA 1000-500 000 copies/mL. Optimal ART for treatment-naive individuals must be durable. OBJECTIVES: The aim of this study was to estimate the efficacy and safety of dolutegravir plus lamivudine at week 48 and compare the efficacy in participants with baseline HIV-1 RNA ≤100 000 copies/mL versus >100 000 copies/mL. METHODS: Virological success was defined as HIV-1 RNA <50 copies/mL by FDA Snapshot criteria. Definition of virological failure included confirmed HIV-1 RNA >200 copies/mL at week 24 or later. The proportion of participants with virological success was estimated using two-sided exact Clopper-Pearson 95% CI. Comparison between screening HIV-1 RNA (≤100 000 versus >100 000 copies/mL) strata was carried out by Fisher's exact test. The study was registered with ClinicalTrials.gov, number NCT02582684. RESULTS: A total of 120 enrolled eligible participants were included in the analysis. At week 48, 102 of the 120 participants (85%; 95% CI 77%-91%) had virological success. Virological success was similar between screening HIV-1 RNA groups. Six (5%) participants had virological non-success and one additional participant experienced virological failure while on study but off study treatment. No new drug resistance mutations were observed. Six (5%) participants had study-related grade 3 or higher adverse events and none discontinued study treatment. CONCLUSIONS: These results add to the evidence that dolutegravir plus lamivudine is a safe and effective option for initial ART in individuals with HIV-1 RNA <500 000 copies/mL.