Intersecting Epidemics: The Predictors of Continued Utilization of HIV Care and Treatment Services During the COVID-19 Outbreak Among People Living with HIV in ZIMBABWE.

Globally, there have been considerable achievements towards HIV care and treatment. AIDS-related deaths have been reduced by 60% since the peak in 2004. Potentially, the fight against the HIV epidemic was made more difficult with the outbreak of COVID-19. Thus, this study examined the implications of COVID-19 in the utilization of HIV care and treatment services among people living with HIV on antiretroviral therapy (ART) in Zimbabwe. The study aimed to identify the critical factors defining the utilization of HIV services at the advent of COVID-19 using the fifth revision of the Anderson Behavioral Model of Healthcare Utilization. The study utilized a concurrent triangulation design of which only one data collection phase was used. The quantitative data was collected from 2,157 people living with HIV on antiretroviral viral therapy through a structured interviewer-administered questionnaire. On the other hand, qualitative data was collected through in-depth interviews. Regarding accessing ART refills, the study findings revealed that adolescents aged 15-19 (aOR = 2.16; 95% CI: 1.18-3.96) had higher odds of utilizing ART refills compared to their counterparts who were aged 20-24. Living in a rural area was associated with higher odds of utilizing the ART refill service (aOR = 2.20; 95% CI: 1.49-3.24). Regarding accessing viral load monitoring adults aged 25-39 (aOR = 0.41; 95% CI: 0.26-0.66) were less likely to utilize viral load monitoring compared to young people aged 20-24. Being vaccinated for COVID-19 was significantly associated with higher odds of utilizing the viral load monitoring service (aOR = 1.97; 95% CI: 1.36-2.87) than those not yet vaccinated. Living in a rural area was associated with higher odds of utilizing viral load monitoring (aOR = 1.50; 95% CI: 1.09-2.08). Regarding tuberculosis preventative therapy, adults aged 25-39 (aOR = 0.30; 95% CI: 0.20-0.47) were less likely to utilize tuberculosis preventative therapy compared to young people aged 20-24. Being vaccinated for COVID-19 was significantly associated with higher odds of utilizing tuberculosis preventative therapy (aOR = 1.59; 95% CI: 1.12-2.25) than those not yet vaccinated. Living in a rural area was associated with higher odds of utilizing tuberculosis preventive therapy (aOR = 1.58; 95% CI: 1.19-2.08). Regarding tuberculosis screening being vaccinated for COVID-19 was significantly associated with higher odds of utilizing tuberculosis screening services (aOR = 1.89; 95% CI: 1.41-2.54) than those not yet vaccinated. Although the severity of the COVID-19 pandemic has dwindled, COVID-19 appears to come and go in waves, and a few countries are still recording relatively high cases. It is therefore likely that the factors associated with utilization of HIV services identified by the study such as age, residence, type of health facility, vaccination of COVID-19 and fear of contracting COVID-19, among others, need to be included when planning to improve access to health utilization.

Integrating 3HP-based tuberculosis preventive treatment into Zimbabwe's Fast Track HIV treatment model: experiences from a pilot study.

INTRODUCTION: Tuberculosis (TB) causes one-third of HIV-related deaths worldwide, making TB preventive treatment (TPT) a critical element of HIV programmes. Approximately 16% of people living with HIV (PLHIV) on antiretrovirals in Zimbabwe are enrolled in the Fast Track (FT) differentiated service delivery model, which includes multi-month dispensing of antiretrovirals and quarterly health facility (HF) visits. We assessed the feasibility and acceptability of utilizing FT to deliver 3HP (3 months of once-weekly rifapentine and isoniazid) for TPT by aligning TPT and HIV visits, providing multi-month dispensing of 3HP, and using phone-based monitoring and adherence support. METHODS: We recruited a purposive sample of 50 PLHIV enrolled in FT at a high-volume HF in urban Zimbabwe. At enrolment, participants provided written informed consent, completed a baseline survey, and received counselling, education and a 3-month supply of 3HP. A study nurse mentor called participants at weeks 2, 4 and 8 to monitor and support adherence and side effects. When participants returned for their routine 3-month FT visit, they completed another survey, and study staff conducted a structured medical record review. In-depth interviews were conducted with providers who participated in the pilot. RESULTS: Participants were enrolled between April and June 2021 and followed through September 2021. Median age = 32 years (IQR 24,41), 50% female, median time in FT 1.8 years (IQR 0.8,2.7). Forty-eight participants (96%) completed 3HP in 13 weeks; one completed in 16 weeks, and one stopped due to jaundice. Most participants (94%) reported "always" or "almost always" taking 3HP correctly. All reported they were very satisfied with the counselling, education, support and quality of care they received from providers and FT service efficiency. Almost all (98%) said they would recommend it to other PLHIV. Challenges reported included pill burden (12%) and tolerability (24%), but none had difficulty with phone-based counselling or wished for additional HF-based visits. DISCUSSION: Using FT to deliver 3HP was feasible and acceptable. Some reported tolerability challenges but 98% completed 3HP, and all appreciated the efficiency of aligning TPT and HIV HF visits, multi-month dispensing and phone-based counselling. CONCLUSIONS: Scaling up this approach could expand TPT coverage in Zimbabwe.

The impact of the COVID-19 pandemic on people living with HIV in Zimbabwe.

The COVID-19 pandemic was reported from March 2020 in Zimbabwe. COVID-19 containment measures which included repeated lockdowns have disrupted community interactions, reduced working hours, restricted travel and restricted HIV services for people living with HIV (PLHIV), among others. The study adopted a cross-sectional design. Both qualitative and quantitative data were collected in all the 10 provinces and analysed. A sample size of 480 was calculated for the cross-sectional survey. Secondary data on HIV early warning indicators from 2018 to 2021 were extracted from 20 randomly selected health facilities and used for modelling. Mathematical modelling was conducted to assess the impact of COVID-19 on PLHIV. AIDS-related deaths increased from 20 100 in 2019 to 22 200 in 2020. In addition, there were significant years of life lost (yLLs) from premature mortality and years of life lost due to disability (yLDs) from COVID-19. Prevalence of COVID-19 among PLHIV was 4%. COVID-19 vaccination coverage was 64%, which is higher than the national average of 42%. Stress and breach of confidentiality as ARV medicines were given out in open spaces and fear of contracting COVID-19 were the perceived psychological issues. COVID-19 disrupted HIV service provision, increased AIDS-related deaths and caused psychological challenges.

Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19.

Importance: Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. Objective: To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. Design, Setting, and Participants: Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. Interventions: Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). Main Outcomes and Measures: Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. Results: Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. Conclusion and Relevance: In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine. Trial Registration: ClinicalTrials.gov Identifier: NCT04436276.

Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial.

BACKGROUND: The development of an effective vaccine against Zika virus remains a public health priority. A Zika purified inactivated virus (ZPIV) vaccine candidate has been shown to protect animals against Zika virus challenge and to be well tolerated and immunogenic in humans up to 8 weeks of follow-up. We aimed to assess the safety and immunogenicity of ZPIV in humans up to 52 weeks of follow-up when given via standard or accelerated vaccination schedules. METHODS: We did a single-centre, double-blind, randomised controlled, phase 1 trial in healthy adults aged 18-50 years with no known history of flavivirus vaccination or infection at Beth Israel Deaconess Medical Center in Boston, MA, USA. Participants were sequentially enrolled into one of three groups: ZPIV given at weeks 0 and 4 (standard regimen), weeks 0 and 2 (accelerated regimen), or week 0 alone (single-dose regimen). Within each group, participants were randomly assigned using a computer-generated randomisation schedule to receive an intramuscular injection of 5 µg ZPIV or saline placebo, in a ratio of 5:1. The sponsor, clinical staff, investigators, participants, and laboratory personnel were masked to treatment assignment. The primary endpoint was safety up to day 364 after final dose administration, and secondary endpoints were proportion of participants with positive humoral immune responses (50% microneutralisation titre [MN50] ≥100) and geometric mean MN50 at observed peak response (ie, the highest neutralising antibody level observed for an individual participant across all timepoints) and week 28. All participants who received at least one dose of ZPIV or placebo were included in the safety population; the analysis of immunogenicity at observed peak included all participants who received at least one dose of ZPIV or placebo and had any adverse events or immunogenicity data after dosing. The week 28 immunogenicity analysis population consisted of all participants who received ZPIV or placebo and had immunogenicity data available at week 28. This trial is registered with ClinicalTrials.gov, NCT02937233. FINDINGS: Between Dec 8, 2016, and May 17, 2017, 12 participants were enrolled into each group and then randomly assigned to vaccine (n=10) or placebo (n=2). There were no serious or grade 3 treatment-related adverse events. The most common reactions among the 30 participants who received the vaccine were injection-site pain (24 [80%]), fatigue (16 [53%]), and headache (14 [46%]). A positive response at observed peak titre was detected in all participants who received ZPIV via the standard regimen, in eight (80%) of ten participants who received ZPIV via the accelerated regimen, and in none of the ten participants who received ZPIV via the single-dose regimen. The geometric mean of all individual participants' observed peak values was 1153·9 (95% CI 455·2-2925·2) in the standard regimen group, 517·7 (142·9-1875·6) in the accelerated regimen group, and 6·3 (3·7-10·8) in the single-dose regimen group. At week 28, a positive response was observed in one (13%) of eight participants who received ZPIV via the standard regimen and in no participant who received ZPIV via the accelerated (n=7) or single-dose (n=10) regimens. The geomteric mean titre (GMT) at this timepoint was 13·9 (95% CI 3·5-55·1) in the standard regimen group and 6·9 (4·0-11·9) in the accelerated regimen group; antibody titres were undetectable at 28 weeks in participants who received ZPIV via the single-dose regimen. For all vaccine schedules, GMTs peaked 2 weeks after the final vaccination and declined to less than 100 by study week 16. There was no difference in observed peak GMTs between the standard 4-week and the accelerated 2-week boosting regimens (p=0·4494). INTERPRETATION: ZPIV was safe and well tolerated in humans up to 52 weeks of follow-up. ZPIV immunogenicity required two doses and was not durable. Additional studies of ZPIV to optimise dosing schedules are ongoing. FUNDING: The Henry M Jackson Foundation for the Advancement of Military Medicine.

Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22).

BACKGROUND: Current efficacy studies of a mosaic HIV-1 prophylactic vaccine require four vaccination visits over one year, which is a complex regimen that could prove challenging for vaccine delivery at the community level, both for recipients and clinics. In this study, we evaluated the safety, tolerability, and immunogenicity of shorter, simpler regimens of trivalent Ad26.Mos.HIV expressing mosaic HIV-1 Env/Gag/Pol antigens combined with aluminium phosphate-adjuvanted clade C gp140 protein. METHODS: We did this randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) at Beth Israel Deaconess Medical Center in Boston, MA, USA. We included healthy, HIV-uninfected participants (aged 18-50 years) who were considered at low risk for HIV infection and had not received any vaccines in the 14 days before study commencement. We randomly assigned participants via a computer-generated randomisation schedule and interactive web response system to one of three study groups (1:1:1) testing different regimens of trivalent Ad26.Mos.HIV (5 × 1010 viral particles per 0·5 mL) combined with 250 µg adjuvanted clade C gp140 protein. They were then assigned to treatment or placebo subgroups (5:1) within each of the three main groups. Participants and investigators were masked to treatment allocation until the end of the follow-up period. Group 1 received Ad26.Mos.HIV alone at weeks 0 and 12 and Ad26.Mos.HIV plus adjuvanted gp140 at weeks 24 and 48. Group 2 received Ad26.Mos.HIV plus adjuvanted gp140 at weeks 0, 12, and 24. Group 3 received Ad26.Mos.HIV alone at week 0 and Ad26.Mos.HIV plus adjuvanted gp140 at weeks 8 and 24. Participants in the control group received 0·5 mL of 0·9% saline. All study interventions were administered intramuscularly. The primary endpoints were Env-specific binding antibody responses at weeks 28, 52, and 72 and safety and tolerability of the vaccine regimens for 28 days after the injection. All participants who received at least one vaccine dose or placebo were included in the safety analysis; immunogenicity was analysed using the per-protocol population. The IPCAVD010/HPX1002 trial is registered with ClinicalTrials.gov, NCT02685020. We also did a parallel preclinical study in rhesus monkeys to test the protective efficacy of the shortened group 3 regimen. FINDINGS: Between March 7, 2016, and Aug 19, 2016, we randomly assigned 36 participants to receive at least one dose of study vaccine or placebo, ten to each vaccine group and two to the corresponding placebo group. 30 (83%) participants completed the full study, and six (17%) discontinued it prematurely because of loss to follow-up, withdrawal of consent, investigator decision, and an unrelated death from a motor vehicle accident. The two shortened regimens elicited comparable antibody titres against autologous clade C Env at peak immunity to the longer, 12-month regimen: geometric mean titre (GMT) 41 007 (95% CI 17 959-93 636) for group 2 and 49 243 (29 346-82 630) for group 3 at week 28 compared with 44 590 (19 345-102 781) for group 1 at week 52). Antibody responses remained increased (GMT >5000) in groups 2 and 3 at week 52 but were highest in group 1 at week 72. Antibody-dependent cellular phagocytosis, Env-specific IgG3, tier 1A neutralising activity, and broad cellular immune responses were detected in all groups. All vaccine regimens were well tolerated. Mild-to-moderate pain or tenderness at the injection site was the most commonly reported solicited local adverse event, reported by 28 vaccine recipients (93%) and two placebo recipients (33%). Grade 3 solicited systemic adverse events were reported by eight (27%) vaccine recipients and no placebo recipients; the most commonly reported grade 3 systemic symptoms were fatigue, myalgia, and chills. The shortened group 3 regimen induced comparable peak immune responses in 30 rhesus monkeys as in humans and resulted in an 83% (95% CI 38·7-95, p=0·004 log-rank test) reduction in per-exposure acquisition risk after six intrarectal challenges with SHIV-SF162P3 at week 54, more than 6 months after final vaccination. INTERPRETATION: Short, 6-month regimens of a mosaic HIV-1 prophylactic vaccine elicited robust HIV-specific immune responses that were similar to responses elicited by a longer, 12-month schedule. Preclinical data showed partial protective efficacy of one of the short vaccine regimens in rhesus monkeys. Further clinical studies are required to test the suitability of the shortened vaccine regimens in humans. Such shortened regimens would be valuable to increase vaccine delivery at the community level, particularly in resource-limited settings. FUNDING: Ragon Institute (Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University; Cambridge, MA, USA) and Janssen Vaccines & Prevention (Leiden, Netherlands).