Raltegravir 1200 mg once daily as maintenance therapy in virologically suppressed HIV-1 infected adults: QDISS open-label trial

Background Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. Methods The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm. Results Of 100 participants 91% maintained viral suppression (95% CI: 83.6–95.8) at week 24 and 89% (81.2–94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3–4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol (p = 0.023) and LDL-cholesterol (p = 0.009) decreased, lifestyle and ease subscale significantly improved (p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 (p = 0.007). Conclusion RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes. Trial registration: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial

Background We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. Methods PBMCs were obtained from 10 HIV+ individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4+ and CD8+ T-cells. Results The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4+ and CD8+ T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4+ T-cells. The number of candidates that increased in vitro the cytokine levels in CD4+ and CD8+ T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. Conclusions MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829, posted November 11th, 2016)

Routine HIV clinic visit adherence in the African Cohort Study

Background Retention in clinical care is important for people living with HIV (PLWH). Evidence suggests that missed clinic visits are associated with interruptions in antiretroviral therapy (ART), lower CD4 counts, virologic failure, and overlooked coinfections. We identified factors associated with missed routine clinic visits in the African Cohort Study (AFRICOS). Methods In 2013, AFRICOS began enrolling people with and without HIV in Uganda, Kenya, Tanzania, and Nigeria. At enrollment and every 6 months thereafter, sociodemographic questionnaires are administered and clinical outcomes assessed. Missed clinic visits were measured as the self-reported number of clinic visits missed in the past 6 months and dichotomized into none or one or more visits missed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and missed visits. Results Between January 2013 and March 2020, 2937 PLWH were enrolled, of whom 2807 (95.6%) had initiated ART and 2771 had complete data available for analyses. Compared to PLWH 50+, missed clinic visits were more common among those 18–29 years (aOR 2.33, 95% CI 1.65–3.29), 30–39 years (aOR 1.59, 95% CI 1.19–2.13), and 40–49 years (aOR 1.42, 95% CI 1.07–1.89). As compared to PLWH on ART for < 2 years, those on ART for 4+ years were less likely to have missed clinic visits (aOR 0.72, 95% CI 0.55–0.95). Missed clinic visits were associated with alcohol use (aOR 1.34, 95% CI 1.05–1.70), a history of incarceration (aOR 1.42, 95% CI 1.07–1.88), depression (aOR 1.47, 95% CI 1.13–1.91), and viral non-suppression (aOR 2.50, 95% CI 2.00–3.12). As compared to PLWH who did not miss any ART in the past month, missed clinic visits were more common among those who missed 1–2 days (aOR 2.09, 95% CI 1.65–2.64) and 3+ days of ART (aOR 7.06, 95% CI 5.43–9.19). Conclusions Inconsistent clinic attendance is associated with worsened HIV-related outcomes. Strategies to improve visit adherence are especially needed for young PLWH and those with depression.

Determinants of viral load non-suppression among adolescents in Mbale District, Eastern Rural Uganda

Background Adolescents are lagging behind in the “third 95” objective of the Joint United Nations Program on HIV/AIDS requiring 95% of individuals on antiretroviral therapy (ART) to have viral load (VL) suppression. This study aimed to describe factors associated with viral non-suppression among adolescents in Mbale district, Uganda. Methods We conducted a retrospective review of routinely collected HIV programme records. Data such as age, education, ART Regimen, ART duration, WHO Clinical stage, comorbidities, etc., were extracted from medical records for the period January 2018 to December 2018. Descriptive analysis was done for continuous variables using means and frequencies to describe study sample characteristics, and to determine the prevalence of outcome variables. We used logistic regression to assess factors associated with VL non-suppression among adolescents. Results The analysis included 567 HIV-infected adolescents, with 300 (52.9%) aged between 13 to 15 years, 335 (59.1%) female, and mean age of 15.6 years (interquartile range [IQR] 13.5–17.8. VL non-suppression was 31.4% (178/567). Male sex (AOR = 1.78, 95% CI 1.06, 2.99; p < 0.01), age 16–19 years (AOR = 1.78, 95% CI 1.06, 2.99; p < 0.05), No formal education (AOR = 3.67, 95% CI 1.48–9.09; p < 0.01), primary education (AOR = 2.23, 95% CI 1.05–2.32; p < 0.01), ART duration of > 12 months to 5 years (AOR = 3.20, 95% CI 1.31–7.82; p < 0.05), ART duration > 5 years (AOR = 3.47, 95% CI 1.39– 8.66; p < 0.01), WHO Clinical Stage II (AOR = 0.48, 95% CI: 0.28, 0.82; p < 0.01), second-line ART regimen (AOR = 2.38, 95% CI 1.53–3.72; p < 0.001) and comorbidities (AOR = 3.28, 95% CI 1.20–9.00; p < 0.05) were significantly associated with viral non-suppression. Conclusions VL non-suppression among adolescents was almost comparable to the national average. VL non-suppression was associated with being male, age 16–19 years, education level, duration on ART therapy, WHO Clinical Staging II, second-line ART regimen, and presence of comorbidities. Adolescent-friendly strategies to improve VL suppression e.g. peer involvement, VL focal persons to identify and actively follow-up non-suppressed adolescents, patient education on VL suppression and demand creation for ART are needed, especially for newly-initiated adolescents and adolescents on ART for protracted periods, to foster attainment of the UNAIDS 95–95–95 targets.

Time to initial highly active antiretroviral therapy discontinuation and its predictors among HIV patients in Felege Hiwot comprehensive specialized hospital: a retrospective cohort study

Background Anti-retroviral therapy regimen discontinuations become a big challenge and cause diminishing the clinical and immunological benefit of treatment in Ethiopia. It reduces both the duration and the chance of viral control due to cross-resistance between different alternative drugs and overlapping toxicity between and within a class of antiretroviral drugs in Ethiopia. However, information’s on the time of initial regimen discontinuation and its predictors are not well studied. Objective This study aimed to assess the time to initial highly active antiretroviral therapy discontinuation and its predictors among HIV patients in Felege Hiwot comprehensive specialized hospital, North West Ethiopia. Method Institution-based retrospective cohort study was conducted among 418 HIV patients who started HAART from January 1, 2014, to December 31, 2019. Data were collected from the patient chart using a data extraction tool. The Kaplan–Meier curve was employed to compare survival rates. Multivariable Cox proportional hazard regression was applied to identify independent predictors of time to initial regimen discontinuation. Result A total of 418 patients on anti-retroviral therapy were followed. Incidence of initial HAART discontinuation was 16.7/100 person year. The median survival time was 3.5 years. Predictors showed association for time to initial HAART discontinuation were taking > 1 ART pills/day (AHR = 4.1, 95% CI 3.0–6.5), baseline CD4 count < 100 cells/mm3 (AHR = 2.6, 95% CI 1.5–4.7), 100–199 cells/mm3 (AHR = 2.2, 95% CI 1.2–4.0), baseline WHO clinical stage IV (AHR = 2.68, 95% CI 1.6–4.3) and stage III (AHR = 2.6, 95% CI 1.4–4.3) and TB infection (AHR = 2.3, 95% CI 1.6–3.5). Conclusion Most of the discontinuation occurred after 1 year of initiation of HAART. Baseline WHO clinical stage, TB infection, baseline CD4 count, and taking > 1 ART pill/day were found predictors of initial HAART regimen discontinuation. Work on early detection of HIV before the disease is advanced and initiation of one ART regimen daily is vital for survival on the initial regimen.

Trends and correlates of HIV prevalence among adolescents in South Africa: evidence from the 2008, 2012 and 2017 South African National HIV Prevalence, Incidence and Behaviour surveys

Background Adolescents are at increased risk of HIV infection compared to other age groups. There is an urgent need for strategic information that will inform programmes to reduce risk and vulnerability to HIV and reverse the pattern of increasing HIV infection as they transition to adulthood. This paper analysed trends and factors associated with HIV prevalence among adolescents in South Africa using the national HIV population-based household surveys conducted in 2008, 2012 and 2017. Methods All three surveys used a multistage cross-sectional design. A trend analysis was conducted to assess the differences in HIV prevalence and covariates overtime using P-trend Chi-squared statistic. Univariate and multivariate logistic regression models were used to determine factors associated with HIV prevalence. Results Overall there was a significant increase in HIV prevalence among adolescents aged 12–19 years from 3.0% (n = 2892) in 2008 to 3.2% (n = 4829) in 2012 and 4.1% (n = 3937) in 2017 (p = 0.031). The odds of being HIV positive among adolescents aged 12–19 years was significantly higher among females [AOR = 2.24; 95% CI (1.73–2.91); p < 0.001] than males, those residing in KwaZulu-Natal province [AOR = 2.01; 95% CI (1.-3.99); p = 0.027] than Northern Cape, and those who did not attend an educational institution and were unemployed [AOR = 2.66; 95% CI (1.91–3.67); p < 0.001] compared to those attending an educational institution. The odds were significantly lower among Whites [AOR = 0.29; 95% CI (0.09–0.93); p = 0.037], Coloureds [AOR = 0.21; 95% CI (0.11–0.37); p ≤ 0.001] and Indian/Asian [AOR = 0.08; 95% CI (0.02–0.34); p = 0.001] population groups than Black Africans. Conclusion The observed increasing trend and gender disparities in HIV prevalence suggests an urgent need for age appropriate and gender specific HIV interventions tailored and targeted at identified drivers of HIV infection among adolescents.

A systematic review and meta-analysis of HIV associated neurocognitive disorders (HAND) among people with HIV in Ethiopia

Background Ethiopia, being in the Sub Saharan region of Africa, is one of the countries with a substantial burden of HIV infection. Because of the high burden of HIV and poor health care settings, HAND is prevalent as demonstrated in various cross-sectional studies. However, no review has been conducted to report the consolidated magnitude of HAND among people with HIV in Ethiopia. Therefore, this systematic review and meta-analysis aimed to estimate the prevalence of HAND in Ethiopia. Methods Following the PRISMA guidelines, we systematically reviewed and meta-analyzed studies that investigated the prevalence of HAND in Ethiopia from PubMed, Google Scholar, Science Direct, HINARI, EMBASE, and Cochrane library databases. We also looked at the reference lists of the included studies to include other relevant studies. Subgroup analysis was performed based on publication year, study location, and sample size. Heterogeneity across studies was evaluated using the I2 test. Potential publication bias was assessed using Egger’s test and visual inspection of symmetry in the funnel plots. Results In the present meta-analysis, 627 articles were initially identified and evaluated. Of these, 8 studies that met the inclusion criteria were included in the final analysis. The pooled prevalence of HAND in people with HIV in Ethiopia was 39.15% (95% CI 29.36, 48.94). The highest prevalence observed in the Southern Nations, Nationalities, and Peoples’ Region (SNNPR) with 53.20% (95% CI 25.96, 80.44) followed by others 34.87% (Tigray, Addis Ababa, and Oromia) (95% CI 33.49, 36.24) and Amhara 34.07% (95% CI 25.39, 42.74).The funnel plot was asymmetrical. However, Egger’s regression tests provided no evidence of publication bias in the prevalence of HAND. Conclusion In this meta-analysis, the pooled prevalence of HAND, in Ethiopia, was high. Older age, substance use, advanced stages of the disease, and lack of education were the main determinants of HAND in Ethiopia. Health education, early screening of people with HIV, and training of health professionals working in hospitals on HAND are highly recommended.

Impact of using creative arts programming to support HIV treatment in adolescents and young adults in Eswatini

Background In 2018, approximately 1.6 million adolescents (aged 10–19) were living with HIV worldwide, with the highest HIV prevalence found in Eswatini. Adolescents and young adults living with HIV are a vulnerable population due to unique psychosocial challenges that come with having a stigmatizing disease. This group struggles more than other age-groups with medication adherence and requires novel approaches to supporting treatment, including peer-group encouragement, and self-expression. Methods We piloted a theater camp for a group of adolescents and young adults enrolled at our HIV clinic in Mbabane, Eswatini, to determine the impact of having an outlet for creative expression and peer support on treatment and feelings of stigma. Pre- and post-camp surveys were administered to the participants to assess perceived stigma and impact of the camp. The results were analyzed using a Wilcoxon-signed rank test. Results Twenty individuals (ages 12–23) living with HIV participated in the camp concurrently with standard treatment. 25% showed a substantial decrease in viral load within six months of completing the camp (> 0.1 log10 change) while only 10% showed a substantial increase. Those who completed the survey felt the camp helped them with confidence, teamwork, and friendships. A comparison of pre- and post- surveys showed an overall decrease in personalized stigma. Quotes from participants reinforced these results. Conclusions Adolescents and young adults living with HIV are an important population for further program development. Our study showed creative arts programming has beneficial psychosocial effects, aids in community building, and potentially enhances the effectiveness of medical treatment. Further programs and studies should continue to investigate creative arts as an avenue for self-expression and community building among vulnerable populations.

Adverse events of inactivated COVID-19 vaccine in HIV-infected adults

This study aims to evaluate the safety of inactivated COVID-19 vaccine among adult people living with HIV (PLWH). In total, 259 PLWH who received at least one dose of inactivated COVID-19 vaccine were enrolled, and post-vaccination adverse events (AEs) were evaluated seven days following each vaccination dose. The overall AE frequency was 22.8% after dose one, which was higher than after dose two (10.2%) (P < 0.001). No severe side event or vaccine safety concern was observed. Our finding was essential in reducing vaccine hesitancy among PLWH.

Renal function in Japanese HIV-1-positive patients who switch to tenofovir alafenamide fumarate after long-term tenofovir disoproxil fumarate: a single-center observational study

Background Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF. Methods A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF. Results Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF. Conclusions In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored.