Safety and Efficacy of SAB-185 for Non-hospitalized Adults with COVID-19: A Randomized Clinical Trial.

BACKGROUND: To address the need for novel COVID-19 therapies, we evaluated the fully-human polyclonal antibody product SAB-185 in a phase 3 clinical trial. METHODS: Non-hospitalized high-risk adults within 7 days of COVID-19 symptom onset were randomized 1:1 to open-label SAB-185 3,840 units/kg or casirivimab/imdevimab 1200 mg. Non-inferiority comparison was undertaken for the pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active). Primary outcomes were the composite of all-cause hospitalizations/deaths and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28. Secondary outcomes included time to sustained symptom improvement and resolution. RESULTS: Enrollment was terminated early due to low hospitalization/death rates upon Omicron emergence. 733 adults were randomized, 255 included in pre-Omicron and 392 in Omicron analysis populations. Hospitalizations/deaths occurred in 6 (5.0%) and 3 (2.2%) of pre-Omicron SAB-185 and casirivimab/imdevimab arms, respectively (absolute difference [95% CI] 2.7% [-2.3%, 8.6%]), inconclusive for non-inferiority; and 5 (2.5%) versus 3 (1.5%) (absolute difference 1.0% [-2.3%, 4.5%]) for Omicron. Risk ratios for grade ≥3 TEAEs were 0.94 [0.52, 1.71] (pre-Omicron) and 1.71 [0.96, 3.07] (Omicron). Time to symptom improvement and resolution were shorter for SAB-185, median 11 vs 14 (pre-Omicron) and 11 vs 13 days (Omicron) (symptom improvement), and 16 vs 24 days and 18 vs >25 days (symptom resolution), p<0.05 for symptom resolution for Omicron only. CONCLUSIONS: SAB-185 had an acceptable safety profile with faster symptom resolution in the Omicron population. Additional studies are needed to characterize its efficacy for COVID-19.

Phase 2 Safety and Antiviral Activity of SAB-185, a Novel Polyclonal Antibody Therapy for Nonhospitalized Adults With COVID-19.

BACKGROUND: SAB-185, a novel fully human IgG polyclonal immunoglobulin product, underwent phase 2 evaluation for nonhospitalized adults with mild-moderate coronavirus disease 2019 (COVID-19). METHODS: Participants received intravenous SAB-185 3840 units/kg (low-dose) or placebo, or 10 240 units/kg (high-dose) or placebo. Primary outcome measures were nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA < lower limit of quantification (LLOQ) at study days 3, 7, and 14, time to symptomatic improvement, and safety through day 28. RESULTS: Two-hundred thirteen participants received low-dose SAB-185/placebo (n = 107/106) and 215 high-dose SAB-185/placebo (n = 110/105). The proportions with SARS-CoV-2 RNA < LLOQ were higher for SAB-185 versus placebo at days 3 and 7 and similar at day 14, and significantly higher at day 7 for high-dose SAB-185 versus placebo only, relative risk 1.23 (95% confidence interval, 1.01-1.49). At day 3, SARS-CoV-2 RNA levels were lower with low-dose and high-dose SAB-185 versus placebo: differences in medians of -0.78 log10 copies/mL (P = .08) and -0.71 log10 copies/mL (P = .10), respectively. No difference was observed in time to symptom improvement: median 11/10 days (P = .24) for low-dose SAB-185/placebo and 8/10 days (P = .50) for high-dose SAB-185/placebo. Grade ≥3 adverse events occurred in 5%/13% of low-dose SAB-185/placebo and 9%/12% of high-dose SAB-185/placebo. CONCLUSIONS: SAB-185 was safe and generally well tolerated and demonstrated modest antiviral activity in predominantly low-risk nonhospitalized adults with COVID-19. Clinical Trials Registration. NCT04518410.

Prevalence of depression among people living with HIV in rural hospitals in South-Western Nigeria-Association with clinico-demographic factors.

Major depression is the most common neuropsychiatric disorder among people living with HIV (PLWH) and is predictive of high morbidity and mortality among them. This study estimated the prevalence and explored factors associated with depression among PLWH in two rural secondary health facilities providing anti-retroviral therapy (ART) services in Southwestern Nigeria between September and December 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to screen and identify PLWH aged 18 years or older with depression. Descriptive statistics, bivariate and multivariate analyses were performed with SPSS version 23. A total of 172 respondents were screened. The prevalence of depression was 16.3% (95% CI 11.1%, 22.7%). Mild, moderate, and moderately severe depression was identified in 17 (9.9%), 8(4.7%) and 3(1.7%) of the participants, respectively. One (0.6%) respondent had suicidal ideation. Of PLWH with any depression, 20/28(71.4%) were within the 40-59 years of age range. None of the participants was on antidepressants. The factor most associated with depression was hypertension, with adjusted odd ratios of 9.8(95% CI 3.5-27.3, p < 0.0001). The study highlights the importance of screening for the severity of depression among PLWH in rural hospitals providing ART services in Africa. PLWH with comorbid hypertension were more likely to suffer from some form of depression.

Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment.

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = - 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = - 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.

Physical Activity Is Associated With Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection.

Background: Cardiovascular comorbidities are risk factors for human immunodeficiency virus (HIV)-associated cognitive impairment. Given differences in cardiometabolic risk profiles between women and men with HIV, we investigated whether associations between cardiometabolic risk factors and prevalent cognitive impairment differ by sex. Methods: Separate logistic regression models were constructed for women and men at entry into a prospective study of older persons with HIV (PWH) to assess the association of cardiometabolic and other risk factors with cognitive impairment. Results: Of 988 participants, 20% were women. Women had higher total cholesterol (194 vs 186 mg/dL; P = .027), hemoglobin A1c (5.9% vs 5.7%; P = .003), and body mass index (30.8 vs 27.4 kg/m2; P < .001) compared with men, and were less physically active (43% vs 55%; P = .005). In a multivariable model, physical activity was associated with lower odds of cognitive impairment in women (odds ratio, 0.35 [95% confidence interval, .15-.80]; P = .013) but not men. Conclusions: Physical activity may have a greater positive impact on cognitive health in women than in men with HIV. This finding should be confirmed in studies examining the longitudinal association between physical activity and incident cognitive impairment in PWH and the effect of interventions that increase physical activity on cognitive impairment in women with HIV.

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.

Dolutegravir Plus Lamivudine Maintains Human Immunodeficiency Virus-1 Suppression Through Week 48 in a Pilot Randomized Trial.

Clinical Trials Registration: NCT02263326.

ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL.

Background: Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine. Methods: A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA ≥1000 and <500000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was the proportion with HIV-1 RNA <50 copies/mL (FDA [US Food and Drug Administration] Snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20 or >200 copies/mL at or after week 24. Dolutegravir levels and drug resistance testing were performed at VF. Results: One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA >100000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm3. Virologic efficacy at week 24 was 108/120 (90%, confidence interval [83%, 95%]), with comparable results in the >100000 copies/mL and ≤100000 copies/mL strata, that is, 89% (75%, 97%) and 90% (82%, 96%), respectively. Three participants with VF, had undetected plasma dolutegravir at ≥1 time points; the M184V and R263R/K mutations developed in 1 participant. Two participants experienced grade 3 possible/probable treatment-related adverse events; none discontinued treatment due to adverse events. Conclusions: Dolutegravir plus lamivudine demonstrated efficacy in individuals with pretreatment HIV-1 RNA up to 500000 copies/mL in this pilot trial, but a participant developed resistance mutations. Clinical Trials Registration: NCT02582684.

Long-Acting Antiretrovirals: Where Are We now?

PURPOSE OF REVIEW: Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. RECENT FINDINGS: Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

Mobile phone use for a social strategy to improve antiretroviral refill experience at a low-resource HIV clinic: patient responses from Nigeria.

In sub-Saharan African areas where antiretroviral (ARV) drugs are not available through community pharmacies, clinic-based pharmacies are often the primary source of ARV drug refills. Social pressure is mounting on treatment providers to adjust ARV refill services towards user-friendly approaches which prioritize patients' convenience and engage their resourcefulness. By this demand, patients may be signalling dissatisfaction with the current provider-led model of monthly visits to facility-based pharmacies for ARV refill. Mobile phones are increasingly popular in sub-Saharan Africa, and have been used to support ARV treatment goals in this setting. A patient-centred response to on-going social pressure requires treatment providers to view ARV refill activities through the eyes of patients who are negotiating the challenges of day-to-day life while contemplating their next refill appointment. Using focus groups of five categories of adult patients receiving combination ARV therapy, we conducted this cross-sectional qualitative study to provide insight into modifiable gaps between patients' expectations and experiences of the use of mobile phones in facility-based ARV refill service at a public HIV clinic in Nigeria. A notable finding was patients' preference for harnessing informal social support (through intermediaries with mobile phones) to maintain adherence to ARV refill appointments when they could not present in person. This evolving social support strategy also has the potential to enhance defaulter tracking. Our study findings may inform the development of ARV refill strategies and the design of future qualitative studies on client-provider communication by mobile phones in under-resourced HIV treatment programmes.

Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study.

BACKGROUND: There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART. METHODS: This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population. RESULTS: We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/µL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P < .001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P < .001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses. CONCLUSIONS: MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss. CLINICAL TRIALS REGISTRATION: NCT01400412.

Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.

Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.

Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum.

The purpose of this study was to examine the impact of early suppressive antiretroviral therapy (ART) on brain structure and neurocognitive outcomes. We conducted an observational study of subjects within 1 year of HIV infection. Ten ART-naïve and 10 ART-suppressed individuals were matched for age and infection duration and age-matched to 10 HIV-seronegative controls. Quantitative brain imaging and neurocognitive data were analyzed. Subjects on suppressive ART had diminished corpus callosum structural integrity on macromolecular and microstructural imaging, higher cerebrospinal fluid percent, higher depression scores, and lower functional performance. Early suppressive ART may alter the trajectory of neurological progression of HIV infection, particularly in the corpus callosum.

Sex-Biased Associations of Circulating Ferroptosis Inhibitors with Reduced Lipid Peroxidation and Better Neurocognitive Performance in People with HIV.

Ferroptosis is implicated in viral neuropathogenesis and may underlie HIV-associated neurocognitive impairment (NCI). Emerging data also suggest differences in brain iron transport by sex. We hypothesized that circulating ferritins that inhibit ferroptosis associate with neurocognitive function and NCI in people with HIV (PWH) in a sex-biased manner. Serum ferritin heavy-chain-1 (FTH1), ferritin light-chain (FTL), and urinary F2-isoprostanes (uF2-isoPs, specific lipid peroxidation marker) were quantified in 324 PWH (including 61 women) with serial global (NPZ-4) and domain-specific neurocognitive testing. Biomarker associations with neurocognitive test scores and NCIs were evaluated by multivariable regression; correlations with uF2-isoPs were also assessed. Higher FTL and FTH1 levels were associated with less NCI in all PWH (adjusted odds ratios 0.53, 95% confidence interval (95% CI) 0.36-0.79 and 0.66, 95% CI 0.45-0.97, respectively). In women, higher FTL and FTH1 were also associated with better NPZ-4 (FTL adjusted beta (ß) = 0.15, 95% CI 0.02-0.29; FTL-by-sex ßinteraction = 0.32, p = 0.047) and domain-specific neurocognitive test scores. Effects on neurocognitive performance persisted for up to 5 years. Levels of both ferritins correlated inversely with uF2-isoPs in women (FTL: rho = -0.47, p < 0.001). Circulating FTL and FTH1 exert sustained, sex-biased neuroprotective effects in PWH, possibly by protecting against iron-mediated lipid peroxidation (ferroptosis). Larger studies are needed to confirm the observed sex differences and further delineate the underlying mechanisms.

A Stepped-Wedge, Cluster-Randomized, Multisite Study of Text Messaging Plus Peer Navigation to Improve Adherence and Viral Suppression Among Youth on Antiretroviral Therapy.

BACKGROUND: To address the need for improved virologic suppression among youth living with HIV (YLH) on antiretroviral treatment (ART), we evaluated peer navigation plus TXTXT daily text message ART reminders. SETTING: YLH aged 15-24 on ART for at least 3 months at six research sites in four Nigerian cities. METHODS: Using a stepped-wedge design, Cluster 1 was non-randomized, while Clusters 2 and 3 were randomized to sequences of routine care (control period) and 48 weeks of the combination intervention (intervention period). The primary endpoint was viral suppression (HIV-1 RNA <200 copies/mL) at week 48 of the intervention. Secondary endpoints included adherence measured by self-report (90% considered adherent). Post-hoc analysis assessed virologic control at <50 copies/mL and <1000 copies/mL. Generalized estimating equations determined the difference between intervention and control periods in the intention-to-treat population. RESULTS: We enrolled 558 YLH and followed 541 over time, mean age 18 years, 53.8% female, 71.7% perinatally infected, and 38.6% virologically non-suppressed at enrollment. For the primary endpoint, the intervention periods displayed a small, non-significant increase in viral suppression < 200 copies/mL (OR = 1.16 [0.88, 1.54], p = 0.297). There was a significant effect of the combination intervention on virologic control <1000 copies/mL (OR = 1.42 [1.03, 1.94], p = 0.030). Self-reported adherence also improved (OR = 2.07 [1.46, 2.95], p < 0.001). CONCLUSION: Peer navigation plus daily text message ART reminders demonstrated limited benefit among ART-experienced, predominantly perinatally-infected YLH, with no significant effect on viral suppression below 200 copies/mL despite improvement in self-reported adherence.

Treatment and comorbidity burden among people living with HIV: a review of systematic literature reviews.

Background: As the human immunodeficiency virus (HIV) treatment landscape continues to evolve, the prolonged life expectancy and long-term exposure to antiretroviral drugs have modified the burden associated with living with HIV. Objective: To better understand the current treatment and comorbidity burden in people living with HIV (PLWH). Methods: Peer-reviewed systematic literature reviews (SLRs) between 2017 and 2020 that included US studies and examined drug adherence/pill burden, resistance burden, or comorbidities in PLWH were identified. Methods and findings were extracted for the overall studies and examined in the subset of US studies. Results: Among 665 publications identified, 47 met the inclusion criteria (drug adherence/pill burden: 5; resistance: 3; comorbidities: 40). While antiretroviral drug adherence levels varied across SLRs, single-tablet regimens (STR) were associated with higher adherence versus multiple-tablet regimens. STRs were also associated with lower risk of treatment discontinuation, higher cost-effectiveness, and lower risk of hospitalization. Longer survival resulted in a high comorbidity burden, with non-AIDS causes accounting for 47% of deaths among PLWH in the US. HIV doubled the risk of cardiovascular disease and was associated with other health problems, including bone and muscle diseases, depression, and cancers. Several antiretroviral regimens were associated with chronic diseases, including cardiometabolic conditions. Lifetime HIV costs are substantially increasing, driven by antiretroviral, adverse event, and comorbidity treatment costs cumulated due to longer survival times. Conclusions: There is a considerable burden associated with HIV and antiretroviral treatment, highlighting the benefits of less complex and safer regimens, and the unmet need for effective preventative interventions.

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/.

The immunogenicity of an HIV-1 gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy.

OBJECTIVE: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). DESIGN: AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4+ T-cell counts greater than 500 cells/µl, and nadir CD4+ T-cell counts greater than 350 cells/µl. METHODS: The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm c). The active and placebo vaccines were administered by intramuscular electroporation. RESULTS: There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4+ and/or CD8+ T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements. CONCLUSION: A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55Gag DNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.

Two-drug regimens for HIV treatment.

Combination therapy with three antiretroviral agents has been integral to successful HIV-1 treatment since 1996. Although the efficacy, adverse effects, and toxicities of contemporary three-drug regimens have improved, even the newest therapies have potential adverse effects. The use of two-drug regimens is one way to reduce lifetime exposure to antiretroviral drugs while maintaining the benefits of viral suppression. Multiple large, randomised trials have shown the virological non-inferiority of certain two-drug regimens versus three-drug comparators, including adverse effect differences that reflect known profiles of the antiretroviral drugs in the respective regimens. Two-drug combinations are now recommended in treatment guidelines and include the first long-acting antiretroviral regimen for the treatment of HIV-1. Recommended two-drug regimens differ in their risks for, and factors associated with, virological failure and emergent resistance. The tolerability, safety, metabolic profiles, and drug interactions of two-drug regimens also vary by the constituent drugs. No current two-drug regimen is recommended for people with chronic hepatitis B virus as none include tenofovir. Two-drug regimens have increased options for individualised care.