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Abstract Background The study aims to investigate the demographic characteristics, the variations in their immune status, and mortality risk among HIV-1 infection long-term non-progressors (LTNP). Methods Eligible LTNP and typical progressors (TP) were recruited in Guangxi by December 2018. Participants were followed up until December 2022, monitoring ART status, CD4+ T cell counts, and survival/death outcomes. Multivariate logistic, Cox regression, and Kaplan-Meier method were employed to scrutinize associated factors and mortality risk of LTNP. Results A total of 212 LTNP and 390 TP were included. LTNP cohort predominantly comprised males (84.43%), those diagnosed with HIV at age ≤ 40 years (93.87%), and those infected through injection drug use (59.91%). The mortality rate of LTNP were lower than TP (12.74% vs. 27.18%). TP had a higher mortality risk compared to LTNP (adjusted hazard ratio [aHR] = 4.051, 95% CI: 2.284–7.186, P

Abstract Background HIV infection and antiretroviral therapy (ART) are associated with bone loss of people living with HIV (PLWH), but limited studies exist on the impacts of ART regimens on bone mineral density (BMD) in China. This study evaluated BMD changes with three common ART regimens: tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV), tenofovir alafenamide (TAF)-containing, and dolutegravir (DTG)-containing (non-TDF/non-TAF) therapies. Methods In this retrospective study, the prevalence of low BMD was analyzed in PLWH who underwent dual-energy X-ray absorptiometry (DXA) before ART initiation. BMD changes were assessed in participants who had follow-up DXA scans after ≥ 1 year of ART with TDF + 3TC + EFV, TAF-containing, or DTG-containing regimens. We used multivariate logistic regression to evaluate the impact of different ART regimens on > 3% BMD reduction, adjusting for demographic and clinical variables that were significant in univariate analysis (P 3% FN and LS BMD reduction (FN: OR 2.91, 95% CI: 1.33 to 6.37, P = 0.009; LS: OR 2.93, 95% CI: 1.17 to 7.32, P = 0.022), while TAF-containing regimens were not independently linked to > 3% BMD loss (P > 0.05). Conclusions TAF-containing and DTG-containing regimens caused less bone loss than TDF + 3TC + EFV, offering safer options for preserving bone health in Chinese PLWH.

Abstract Background Nigeria adapted the WHO package of care for Advanced HIV Disease (AHD) in 2020. The package includes CD4 + cell count testing to identify People Living with HIV (PLHIV) with AHD, screening and treatment of opportunistic infections, rapid antiretrovirals (ART) initiation, and intensive adherence follow-up. The national program adopted a phased approach in the rollout of the AHD package of care to learn lessons from a few representative health facilities before scaling up across the country. This study describes the process and lessons learned from the first phase of implementation. Methods This was a prospective observational study, and participants were enrolled between February and September 2021. Healthcare-worker (HCW) capacity was built to implement the AHD package of care. The study population included newly diagnosed PLHIV ≥ 10 years presenting to care in 28 selected facilities across 4 states in Nigeria. Eligible participants received CD4 + cell testing at baseline. Those with CD4 + cell count

Abstract Background Human Immune Deficiency Virus (HIV) remains the leading cause of morbidity and mortality globally. It can lead to Acquired Immunodeficiency Syndrome (AIDS), which results in gradual deterioration and failure of the immune system. As the immune system becomes compromised, the patient becomes highly susceptible to life-threatening infection which ends with early death. Even though Antiretroviral Therapy (ART) significantly decreases mortality as a whole, the rate of death is still the highest, especially in the first and second years of ART initiation. The study aims to assess the survival and predictors of mortality among HIV-infected adults after initiation of antiretroviral therapy in Jigjiga City Governmental Hospitals, Eastern Ethiopia. Method Institution-based Retrospective follow-up study was employed among ART patients from January 1, 2015, to December 31, 2021. Data were cleaned and entered in Epi-data version 3.1 and exported to STATA 14 for further analysis. Kaplan–Meier and Log-Rank tests were applied to compare survival differences among categories of different variables. In bi-variable analysis, P-values

Abstract Introduction Opportunistic infections (OIs) are more common and severe among people with suppressed immunity like those living with HIV/AIDS (PLWH). This study aimed to assess the prevalence of OIs and associated factors among PLWH attending antiretroviral therapy (ART) clinics in the Gedeo zone, Southern Ethiopia. Methods A facility based retrospective cohort study was conducted from April to June 2018 among PLWH attending ART clinics in Gedeo zone, Ethiopia from November 2016 – November 2017. A simple random sampling method was used to select the both paper based and electronic study participants’ charts. Adjusted odds ratios were calculated using multivariable logistic regression analysis for variables statistically significant at 95% confidence interval under bivariable logistic regression analysis, and significance was declared at P

Abstract Background While there is no cure for HIV, adherence to antiretroviral therapy can extend the lifespan and improve the quality of life of people with HIV. Despite the global reduction of HIV infection rates in recent years, New York City and La Romana, Dominican Republic, continue to report high infection rates among Latino populations. Many people with HIV remain virally unsuppressed in these geographic hotspots, suggesting a need for additional interventions to overcome medication adherence barriers. Tailored and culturally appropriate mobile health (mHealth) technology can be an engaging way to improve adherence. The primary objective of this trial is to test the effectiveness of an mHealth tool to improve HIV medication adherence among Spanish-speaking people living in New York City and the Dominican Republic. Methods The WiseApp study is a two-arm randomized controlled trial among 248 people with HIV across the New York and Dominican Republic sites over the course of 12 months. Participants are randomly assigned to either receive a CleverCap pill bottle that is linked to the WiseApp (intervention) or standard of care (control). All participants complete surveys at baseline, 3-month, 6-month, and 12-month follow-up visits and the study team obtains HIV-1 viral load and CD4 count results through blood draw at each study timepoint. Discussion The use of mHealth technologies to improve medication adherence among people with HIV has been implemented in recent years. Although some studies have found improvement in adherence to antiretroviral therapy in the short term, there is limited information about how these interventions improve adherence among Spanish-speaking populations. Disproportionate rates of HIV infection among Latinos in New York City suggest an existing inequitable approach in reaching and treating this population. Due to a lack of mHealth studies with Latino populations, and apps tailored to Spanish-speakers, the WiseApp study will not only demonstrate the effectiveness of this particular mHealth app but will also contribute to the mHealth research community as a whole. Trial registration This trial was registered with Clinicaltrials.gov (NCT05398185) on 5/31/2022.

Abstract Background Low-adherence to Anti-retroviral therapy (ART) negatively affects the clinical, immunological, and virologic outcomes of patients. Adherence is the most important factor in determining Antiretroviral Therapy (ART) treatment success and long-term viral suppression which ultimately reduces morbidity and mortality. Thus, this study aimed to identify factors affecting adherence to antiretroviral therapy among adolescents and youth living with HIV. Methods Facility-based cross-sectional study was conducted from March 21 to April 30, 2020 among 316 respondents in selected five high-loaded hospitals with adolescent and youth clients using systematic random sampling technique. Patients’ adherence was assessed when they had reportedly taken 95% or higher of their prescribed antiretroviral drugs in the five days before the interview. Data were collected, entered into EPI Data and exported to SPSS for analysis. Binary logistic regression was used to see the association between dependent and independent variables. Results In this study, 316 respondents participated in the study, with a 99.7% response rate. The mean age of respondents were 17.94 years and majority of them (58.5%) were females. The overall ART adherence among adolescents and youths was found to be 70.6%. Being female (AOR = 0.323, 95% CI, 0.164–0.637), presence of opportunistic infection (AOR = 0.483, 95% CI, 0.249–0.936), taking additional medication beside ART (AOR = 0.436, 95% CI, 0.206–0.922) and availability of youth friendly services within the facility (AOR = 2.206, 95% CI, 1.031–4.721) were found to be predictors. Conclusion The adherence rate in this study was low which is below the recommended adherence level. Being female, taking additional medication beside ART and presence of opportunistic infection were determinants of adherence. As a result, significant work must be done on opportunistic infection prevention through health education and promotion for screening and risk reduction. Similarly, adolescents and youths service integration with the ART Clinic is strongly advised.

Abstract Background This study evaluated the effect of revisions to existing peer-counselor services, called Mentor Mothers (MM), at maternal and child health clinics on medication adherence for women living with HIV (WLWH) in Kenya and on early infant HIV testing. Methods The Enhanced Mentor Mother Program study was a 12-site, two-arm cluster-randomized trial enrolling pregnant WLWH from March 2017 to June 2018 (with data collection through September 2020). Six clinics were randomized to continued MM-supported standard care (SC). Six clinics were randomized to the intervention arm (INT = SC plus revised MM services to include more one-on-one interactions). Primary outcomes for mothers were defined as: (PO1) the proportion of days covered (PDC) with antiretroviral therapy (ART) ≥ 0.90 during the last 24-weeks of pregnancy; and (PO2) ≥ 0.90 PDC during the first 24-weeks postpartum. Secondary outcomes were infant HIV testing according to national guidelines (at 6, 24, and 48 weeks). Crude and adjusted risk differences between study arms are reported. Results We enrolled 363 pregnant WLHV. After excluding known transfers and subjects with incomplete data extraction, data were analyzed for 309 WLWH (151 SC, 158 INT). A small share achieved high PDC during the prenatal and postnatal periods (0.33 SC/0.24 INT achieved PO1; 0.30 SC/0.31 INT achieved PO2; crude or adjusted risk differences were not statistically significant). In addition, ~ 75% in both study arms completed viral load testing during year two after enrollment, with > 90% suppressed in both arms. For infants, ≥ 90% in both arms had at least one HIV test through study follow up (76 weeks) but testing on schedule according to PMTCT guidelines was uncommon. Conclusions While national guidelines in Kenya recommended that all HIV-infected pregnant women take a daily antiretroviral regimen for life following a HIV diagnosis, results presented here indicate that a minor share achieved high medication coverage during the prenatal and postnatal periods analyzed. In addition, adjustments to Mentor-Mother services showed no improvement in study outcomes. The lack of effect for this behavioral intervention is relatively consistent with the existing literature to improve mother-infant outcomes along the PMTCT care cascade. Clinical Trial Number NCT02848235. Date of first trial registration 28/07/2016.

Abstract Background Several studies have shown different effects of telehealth interventions on adherence to Antiretroviral therapy (ART) among people living with HIV. This study conducted a meta-analysis of Randomized Controlled Trials (RCTs) to estimate the pooled effect of telehealth interventions on the treatment adherence of HIV patients. Methods The researchers conducted literature searches in Scopus, PubMed, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials databases. In addition, open grey was systematically searched until January 2022 for RCTs around the effects of telehealth on adherence to treatment ART among patients with HIV. Each study’s methodological quality was assessed using the Cochrane Collaboration tool. Pooled Standard Mean Differences (SMD) and Risk Ratio (RR) with 95% CI were calculated using the random effects model. Results In total, 12 eligible articles were considered in the present systematic review. A random-effects meta-analysis using 5 RCTs yielded the pooled RR estimate of 1.18 (95% CI: 1.03 to 1.35, p

Abstract Purpose Despite antiviral therapy (ART), 800,000 deaths still occur yearly and globally due to HIV infection. In parallel with the good virological control and the aging of this population, multiple comorbidities [HIV-associated-non-AIDS (HANA) conditions] may now be observed. Methods HIV adult patients hospitalized in intensive care unit (ICU) from all the French region from university and non-university hospital who participate to the OutcomeRea™ database on a voluntary basis over a 24-year period. Results Of the 24,298 stays registered, 630 (2.6%) were a first ICU stay for HIV patients. Over time, the mean age and number of comorbidities (diabetes, renal and respiratory history, solid neoplasia) of patients increased. The proportion of HIV diagnosed on ICU admission decreased significantly, while the median duration of HIV disease as well as the percentage of ART-treated patients increased. The distribution of main reasons for admission remained stable over time (acute respiratory distress > shock > coma). We observed a significant drop in the rate of active opportunistic infection on admission, while the rate of active hemopathy (newly diagnosed or relapsed within the last 6 months prior to admission to ICU) qualifying for AIDS increased—nonsignificantly—with a significant increase in the anticancer chemotherapy administration in ICU. Admissions for HANA or non-HIV reasons were stable over time. In multivariate analysis, predictors of 60-day mortality were advanced age, chronic liver disease, past chemotherapy, sepsis-related organ failure assessment score > 4 at admission, hospitalization duration before ICU admission > 24 h, AIDS status, but not the period of admission. Conclusion Whereas the profile of ICU-admitted HIV patients has evolved over time (HIV better controlled but more associated comorbidities), mortality risk factors remain stable, including AIDS status.

Abstract Background Interruption in Treatment (IIT) is a challenge in HIV care and treatment programs in sub- Saharan Africa. High IIT among HIV adolescents has both individual and potential public health consequences including discontinuation of treatment, increased HIV transmission and risk of death. In this era of test and treat policy it is important to ensure that patients remain connected to HIV clinics to enable achieve UNAIDS 95-95-95 targets timely. This study aimed to assess risk factors for IIT among HIV-positive adolescence in Tanzania. Methods We conducted retrospective longitudinal cohort study using secondary data of adolescent patients enrolled in care and treatment clinics in Tanga from October 2018 to December 2020. We defined Interuption in Treatment as missing clinic visits for 90 consecutive days after the last scheduled appointment date on anti-retroviral therapy (ART). Cox proportional hazard regression models were employed to identify risk factors of the outcome variable. Results Among 2,084 adolescents of age between 15 and 19 years were followed for two years, whereby 546 (26.2%) had interrupted treatment. The median age of the participants was 14.6 years (interquartile range, IQR: 12.6–16.6 years), with age between 15 and 19 years, male sex, with advanced HIV disease and were not on Dolutegravir (DTG) related regimens were associated with interruption in treatment; (Hazard ratio (HR) 1.43, 95% CI: 1.23–1.66, p

Abstract The development of antiretroviral therapy (ART) has been effective in suppressing HIV replication. However, severe drug toxicities due to the therapy and its failure in targeting the integrated proviral genome have led to the introduction of a new paradigm of gene-based therapies. With its effective inhibition and high precision, clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) or CRISPR/Cas9 has emerged as an effective genome editing tool in the last decade. Mediated by guide RNAs (gRNAs), Cas9 endonuclease acts like genetic scissors that can modify specific target sites. With this concept, CRISPR/Cas9 has been used to target the integrated proviral HIV-1 genome both in in vitro as well as in vivo studies including non-human primates. The CRISPR has also been tested for targeting latent HIV-1 by modulating the proviral transcription with the help of a specialized Cas9 mutant. Overcoming the limitations of the current therapy, CRISPR has the potential to become the primary genome editing tool for eradicating HIV-1 infection. In this review, we summarize the recent advancements of CRISPR to target the proviral HIV-1 genome, the challenges and future prospects.

Abstract Background Previous clinical data have shown that raltegravir-based antiretroviral therapy (ART) with fewer drug-drug interactions (DDIs) and adverse events (AEs) is a good regimen in patients with HIV infection who need cancer chemotherapy. There are currently few data on ART regimens that include Integrase inhibitors (INSTIs) other than RAL among this patient subgroup. Methods We evaluated the safety and efficacy of different kinds of INSTI-based regimens among patients with HIV and concomitant colorectal cancer (CRC) who received antineoplastic agents. Results From January 2020 to November 2021, 66 patients were enrolled. The patients were divided into three groups: 20 patients treated with dolutegravir (DTG)/lamivudine (3TC)/tenofovir (TDF) (group I), 24 patients treated with DTG/albuvirtide (ABT) (group II), and 22 patients treated with bictegravir (BIC)/tenofovir alafenamide (TAF)/emtricitabine (FTC) (group III). The majority of AEs during treatment were of grade 1–2. Treatment‐related AEs of grade 3–4 occurred in 6 patients (9.09%), and no grade 5 AEs occurred. The most common AEs were nausea (100%) and neutrophils (84.85%) attributed to anticancer agents, and there was no significant difference in the incidence of these AEs among the three groups (P > 0.05). Viral load rebound was not observed among pretreated patients during chemotherapy. The viral load of untreated patients who started their ART concomitant with chemotherapy almost decreased to the lower limit of detection 6 months after ART initiation (only one patient in group III had a viral load of 102 copies/ml). At the 6th month, the CD4 count in group I decreased significantly from baseline (P

Abstract Background Viral suppression remains the most desired outcome in the management of patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and this can be achieved by an effective Antiretroviral Therapy (ART). However, some patients who achieve viral suppression may experience viral rebound with dire consequence. We evaluated viral suppression and rebound and their associated factors among adult patients on ART in Kumasi, Ghana. Methods This hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital in Ghana. We reviewed the medical records of 720 HIV patients on ART. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism version 8.0. p

Abstract Background Multi-month dispensing (MMD) of antiretroviral therapy (ART) represents one approach of differentiated service delivery (DSD) aiming to improve quality and cost-effectiveness for HIV services in resource-limited settings. However, reduction in clinic visits for people living with HIV (PLWH) should go along with out-of-clinic care tailored to PLWH`s preferences and comorbidities to maintain quality of care. eHealth supported MMD offers a potential solution. Methods Between October 2019 and January 2020 we assessed preferences on an eHealth supported MMD package among adult PLWH attending routine ART care at a rural clinic in Lesotho using a mixed-methods approach. Participants reported their preferences among different refill and eHealth options. They were invited to test automated text messages (SMS) informing about their viral load results, an automated tuberculosis symptoms screening call and telemedical support by an expert nurse. Telemedical service comprised a call-back option if participants required any additional support and adherence counselling for closer follow-up of participants with unsuppressed viral loads. After 6 weeks, participants were followed-up to assess perception of the chosen eHealth support using a qualitative approach. Results Among 112 participants (median age = 43 years; 74% female), 83/112 (75%) preferred MMD for 6–12 months (median = 9 months, IQR = [5, 12]). Neither sex, age, employment, costs and time for travel to clinic, nor the duration of taking ART correlated with the MMD preference. All 17 participants attending routine viral load measurement wished to receive the result via SMS. Fifteen (19.2%) participants requested a telemedical nurse call-back during the study period. All participants with recent unsuppressed viral load (N = 13) requested telemedical adherence counselling for closer follow-up. Among 78 participants followed-up, 76 (97%) would appreciate having the call-back option in future. Seventy-five participants (67%) received and evaluated the automated symptomatic tuberculosis screening call, overall 71 (95%) appreciated it. Conclusions The great majority of PLWH in this study preferred 6–12 months MMD and appreciated the additional eHealth support, including viral load results via SMS, telemedical nurse consultations and automated tuberculosis symptom screening calls. eHealth supported MMD packages appear to be a promising approach for DSD models and should be assessed for clinical endpoints and cost-effectiveness in larger studies.

Abstract Background Pretreatment drug resistance (PDR) can limit the effectiveness of HIV antiretroviral therapy (ART). The aim of this study was to assess the prevalence of PDR among HIV-positive individuals that initiated antiretroviral therapy in 2014–2020 in southwestern China. Methods Consecutive cross-sectional surveys were conducted in Qinzhou, Guangxi. We obtained blood samples from individuals who were newly diagnosed with HIV in 2014–2020. PDR and genetic networks analyses were performed by HIV-1 pol sequences using the Stanford HIV-database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression models were used to explore the potential factors associated with PDR. Results In total, 3236 eligible HIV-positive individuals were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that of NRTI (1.7%, p

Abstract Introduction Since the development of antiretroviral therapy (ART) with TDF plus 3TC plus EFV, this specific regimen has not been studied enough with long-term lipid and uric acid monitoring. Methods A prospective follow-up cohort study was performed. Sixty-one treatment-naive male patients with human immunodeficiency virus (HIV) were divided into three groups based on their baseline CD4+ cell count (26, 12, and 23 patients in the 350 groups, respectively). The lipid and purine metabolism parameters of the patients over 144 weeks were analyzed. Result Within 144 weeks, TG, LDL-c, TC and HDL-c gradually increased, especially TC and HDL-c (P = 0.001, 0.000, respectively). Moreover, the percentages of hyper-cholesterolemia, hyper LDL cholesterolemia, hyper-triglyceridemia and low HDL cholesterolemia also gradually increased, especially low HDL cholesterolemia significantly increased (P = 0.0007). The lower the baseline CD4+ cell counts were, the higher the TG levels and the lower the TC, LDL-c and HDL-c levels were. But there was significant difference of only baseline LDL-c levels between the three groups (P = 0.0457). No significant difference of the UA level and the percentages of hyperuricemia was found between the different follow-up time point groups or between the three CD4+ cell counts groups (all P > 0.05). The risk factors for dyslipidemia included age, anthropometric parameters and follow-up weeks, and for hyperuricemia was virus load. Conclusions Gradual increasing dyslipidemia was found in male patients with human immunodeficiency virus primarily treated with tenofovir plus lamivudine plus efavirenz for 3 years. There-fore lipid metabolism parameters should be closely monitored during long-term ART with the TDF plus 3TC plus EFV regimen.

Abstract Background HIV-related maternal deaths and HIV infection among infants remain unacceptably high across sub-Saharan Africa despite increased antenatal care attendance and provision of antiretroviral therapy to pregnant women. In the Jamii Bora (“Better Family” in Swahili) Study, we seek to test the efficacy of an interdependence theory-based couple intervention. The intervention reaches pregnant women and male partners through home visits by male-female pairs of lay health workers. The aim is to increase access to home-based couples’ HIV testing and counseling services to improve family health. Methods This is a three-arm randomized control trial among 1080 pregnant women 15 years of age or older, living with their male partners, and who have not undergone couples’ HIV testing and counseling in Kisumu and Migori Counties in Kenya. Couples will be randomized into three groups: home-based couple visits, HIV self-testing kits for couple use, or standard care (male partner clinic invitation letters). Participants will be followed up to 18 months postpartum. The study has three aims: in aim 1, we will determine the effects of the intervention on our primary outcome of couple HIV testing, compared to HIV self-testing kits and standard care; in aim 2, we will examine the intervention impact on HIV prevention behaviors, facility delivery, and postnatal healthcare utilization, as well as secondary health outcomes of maternal viral suppression and HIV-free child survival up to 18 months for couples living with HIV; and in aim 3, we will compare the cost-effectiveness of the home-based couple intervention to the less resource-intensive strategies used in the other two study arms. Assessments with couples are conducted at baseline, late pregnancy, and at months 3, 6, 12, and 18 after birth. Discussion The results from this study will inform decision-makers about the cost-effective strategies to engage pregnant couples in the prevention of mother-to-child transmission and family health, with important downstream benefits for maternal, paternal, and infant health. Trial registration ClinicalTrials.gov NCT03547739 . Registered on May 9, 2018

Abstract Background Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. Methods We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design. Results Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high–level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens. Conclusions DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.

Abstract Background Over the last decade, the Kenyan HIV treatment program has grown exponentially, with improved survival among people living with HIV (PLHIV). In the same period, noncommunicable diseases (NCDs) have become a leading contributor to disease burden. We sought to characterize the burden of four major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes mellitus) among adult PLHIV in Kenya. Methods We conducted a nationally representative retrospective medical chart review of HIV-infected adults aged ≥15 years enrolled in HIV care in Kenya from October 1, 2003 through September 30, 2013. We estimated proportions of four NCD categories among PLHIV at enrollment into HIV care, and during subsequent HIV care visits. We compared proportions and assessed distributions of co-morbidities using the Chi-Square test. We calculated NCD incidence rates and their confidence intervals in assessing cofactors for developing NCDs. Results We analyzed 3170 records of HIV-infected patients; 2115 (66.3%) were from women. Slightly over half (51.1%) of patient records were from PLHIVs aged above 35 years. Close to two-thirds (63.9%) of PLHIVs were on ART. Proportion of any documented NCD among PLHIV was 11.5% (95% confidence interval [CI] 9.3, 14.1), with elevated blood pressure as the most common NCD 343 (87.5%) among PLHIV with a diagnosed NCD. Despite this observation, only 17 (4.9%) patients had a corresponding documented diagnosis of hypertension in their medical record. Overall NCD incidence rates for men and women were (42.3 per 1000 person years [95% CI 35.8, 50.1] and 31.6 [95% CI 27.7, 36.1], respectively. Compared to women, the incidence rate ratio for men developing an NCD was 1.3 [95% CI 1.1, 1.7], p = 0.0082). No differences in NCD incidence rates were seen by marital or employment status. At one year of follow up 43.8% of PLHIV not on ART had been diagnosed with an NCD compared to 3.7% of patients on ART; at five years the proportions with a diagnosed NCD were 88.8 and 39.2% (p

Abstract Background The WHO guidelines for the management of advanced HIV disease recommend a package of care consisting of rapid initiation of antiretroviral therapy (ART), enhanced screening and diagnosis of tuberculosis (TB) and cryptococcal meningitis, co-trimoxazole prophylaxis, isoniazid preventive therapy (IPT), fluconazole pre-emptive therapy, and adherence support. The goals of this study were to determine the prevalence of advanced HIV disease among individuals initiating ART in Senegal, to identify predictors of advanced disease, and to evaluate adherence to the WHO guidelines. Methods This study was conducted among HIV-positive individuals initiating ART in Dakar and Ziguinchor, Senegal. Clinical evaluations, laboratory analyses, questionnaires and chart review were conducted. Logistic regression was used to identify predictors of advanced disease. Results A total of 198 subjects were enrolled; 70% were female. The majority of subjects (71%) had advanced HIV disease, defined by the WHO as a CD4 count

Abstract Background WHO recommends that HIV infected women receive antiretroviral therapy (ART) minimally during pregnancy and breastfeeding (“Option B”), or ideally throughout their lives regardless of clinical stage (“Option B+”) (Coovadia et al., Lancet 379:221–228, 2012). Although these recommendations were based on clinical trials demonstrating the efficacy of ART during pregnancy and breastfeeding, the population-level effectiveness of Option B+ is unknown, as are retention on ART beyond the immediate post-partum period, and the relative impact and cost-effectiveness of Option B+ compared to Option A (Centers for Disease Control and Prevention, Morb Mortal Wkly Rep 62:148–151, 2013; Ahmed et al., Curr Opin HIV AIDS 8:473–488, 2013). To address these issues, we conducted an impact evaluation of Zimbabwe’s prevention of mother to child transmission programme conducted between 2011 and 2018 using serial, community-based cross-sectional serosurveys, which spanned changes in WHO recommendations. Here we describe the rationale for the design and analysis. Methods/design Our method is to survey mother-infant pairs residing in the catchment areas of 157 health facilities randomly selected from 5 of 10 provinces in Zimbabwe. We collect questionnaires, blood samples from mothers and babies for HIV antibody and viral load testing, and verbal autopsies for deceased mothers/babies. Using this approach, we collected data from two previous time points: 2012 (pre-Option A standard of care), 2014 (post-Option A / pre-Option B+) and will collect a third round of data in 2017–18 (post Option B+ implementation) to monitor population-level trends in mother-to-child transmission of HIV (MTCT) and HIV-free infant survival. In addition, we will collect detailed information on facility level factors that may influence service delivery and costs. Discussion Although the efficacy of antiretroviral therapy (ART) during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (PMTCT) has been well-documented in randomized trials, little evidence exists on the population-level impact and cost-effectiveness of Option B+ or the influence of the facility on implementation (Siegfried et al., Cochrane Libr 7:CD003510, 2017). This study will provide essential data on these gaps and will provide estimates on retention in care among Option B+ clients after the breastfeeding period. Trial registration NCT03388398 Retrospectively registered January 3, 2018.

Abstract Background Gut microbiome characteristics associated with HIV infection are of intense research interest but a deep understanding has been challenged by confounding factors across studied populations. Notably, a Prevotella-rich microbiome described in HIV-infected populations is now understood to be common in men who have sex with men (MSM) regardless of HIV status, but driving factors and potential health implications are unknown. Results Here, we further define the MSM-associated gut microbiome and describe compositional differences between the fecal microbiomes of Prevotella-rich MSM and non-MSM that may underlie observed pro-inflammatory properties. Furthermore, we show relatively subtle gut microbiome changes in HIV infection in MSM and women that include an increase in potential pathogens that is ameliorated with antiretroviral therapy (ART). Lastly, using a longitudinal cohort, we describe microbiome changes that happen after ART initiation. Conclusions This study provides an in-depth characterization of microbiome differences that occur in a US population infected with HIV and demonstrates the degree to which these differences may be driven by lifestyle factors, ART, and HIV infection itself. Understanding microbiome compositions that occur with sexual behaviors that are high risk for acquiring HIV and untreated and ART-treated HIV infection will guide the investigation of immune and metabolic functional implications to ultimately target the microbiome therapeutically.

Abstract Background Adolescents living with HIV on antiretroviral therapy (ART) have worse treatment adherence, viral suppression, and mortality rates compared to adults. This study investigated factors associated with viral non-suppression among adolescents living with HIV in Cambodia. Methods A cross-sectional study was conducted in August 2016 among 328 adolescents living with HIV aged 15–17 years who were randomly selected from 11 ART clinics in the capital city of Phnom Penh and 10 other provinces. Clinical and immunological data, including CD4 count and viral load, were obtained from medical records at ART clinics. Adolescents were categorized as having achieved viral suppression if their latest viral load count was 672 (AOR = 0.47, 95% CI 0.26–0.86), had a relative as the main daily caregiver (AOR = 0.37, 95% CI 0.17–0.80), and did not believe that there is a cure for AIDS (AOR = 0.40, 95% CI 0.21–0.75) compared to their reference group. The likelihood of having viral non-suppression also remained significantly higher among adolescents who had first viral load > 628 RNA copies/mL (AOR = 1.81, 95% CI 1.05–4.08) and among those who were receiving HIV care and treatment from an adult clinic (AOR = 2.95, 95% CI 1.56–5.59). Conclusions The proportion of adolescents living with HIV with viral suppression in this study was relatively high at 76.8%, but falls short of the global target of 90%. Programs targeting younger adolescents and adolescents in transition from pediatric to adult care with a range of interventions including psychosocial support and treatment literacy could further improve viral suppression outcomes.

Abstract Background Despite substantial advances in antiretroviral therapy (ART) for human immunodeficiency virus (HIV) in the last decades, non-adherence (NA) continues to be a major challenge in the real-life treatment. To meet this challenge, adherence-promoting interventions with a tailored approach towards patient-specific adherence barriers that are identified using a reliable and practicable questionnaire are needed. The aim of this investigation was to develop and validate a respective questionnaire (Adherence Barriers Questionnaire for HIV: ABQ-HIV), based on an earlier version of the ABQ. Methods The existing ABQ was discussed by an expert panel and revised according to the specifications of ART therapy for HIV patients. Initially, the ABQ-HIV consisted of 17 items formulated as statements (4-point-Likert-scale ranging from “strongly agree” to “strongly disagree”). A higher score indicates a higher influence of a certain barrier on patient’s perceptions. The ABQ-HIV was applied in a cross-sectional survey of German HIV patients. Evaluation of the questionnaire included an assessment of internal consistency as well as factor analysis. Convergent validity was assessed by comparing the ABQ-HIV score with the degree of self-reported adherence measured by the 8-item Morisky Medication Adherence Scale (MMAS-8©). Results Three hundred seventy patients were able to be included in all validation analyses. The included patients had a mean age of 51.2 years, and 15.7% were female. The mean HIV infection time was 11.7 years, and the mean duration of treatment since first starting ART was 8.7 years. Twenty-five patients – excluded from all further analyses - were not able/willing to answer all ABQ-HIV questions. The results of the reliability analysis showed a Cronbach’s α of 0.708 for the initial 17-items in the ABQ-HIV draft. Two items were eliminated from the initial questionnaire, resulting in a Cronbach’s α of 0.720 and a split-half reliability of 0.724 (Spearman–Brown coefficient). Based on the reduced 15-item scale, the factor analysis resulted in three different components of the questionnaire. Component 1, with seven items, represents the unintentional adherence barriers. The second component, which contains five items, can be labelled as a subscale describing barriers associated with disease/treatment knowledge. Finally, three items, which can be summarized as intentional adherence barriers, show maximum loading in the third component. The score of the reduced 15-item ABQ-HIV scale, as well as the scores of the three subscales, correlated significantly with the MMAS score. All correlation coefficients were negative, indicating that higher burdens of adherence barriers measured by ABQ-HIV or its subscales were associated with a lower MMAS score and thus, with a lower adherence level. The ROC analysis using the MMAS low adherence classification as its state variable provided a cut-off for the ABQ-HIV scale of > 28 (sensitivity: 61.5%, specificity: 83.3%). In our sample, 85 patients (23.0%) reached a score of > 28 and appeared to face a high non-adherence risk. Conclusions The ABQ-HIV is a practical, reliable, and valid instrument for identifying patient-specific barriers to adherence in the HIV treatment. It is also useful in identifying HIV patient subgroups, according to adherence barriers specific to these patients.

Abstract Background HIV infection among youth in the United States is on the rise. A high level of antiretroviral therapy (ART) adherence is crucial to treatment success and can minimize the population burden of the disease. However, the overall rate of ART adherence among youth is generally suboptimal and no published efficacious interventions exist to address the specific needs of this population. This paper describes the design of a stepped-care, “adaptive” ART adherence intervention protocol for HIV-infected adolescents and young adults. Methods This is a randomized controlled trial (RCT) to establish the efficacy of “Positive STEPS,” a behavioral and technology-based intervention to optimize ART adherence and viral suppression among HIV-infected youth, ages 16 to 29. Participants are equally randomized to 1) the Positive STEPS intervention, which begins with two-way daily text messaging as a reminder system to take their medications; participants progress to a more intensive in-person counseling intervention if text messaging is not sufficient to overcome barriers; or 2) or standard of care (SOC). At randomization, all participants receive standardized ART adherence education. During the 4 major study assessment visits (baseline, 4-, 8-, and 12-months), participants have their blood drawn to measure HIV viral load and complete a mix of computer-based self-administered and interviewer-administered behavioral and psychosocial measures. The primary outcomes are improvements in viral load and ART adherence measured via a medication-tracking device (i.e., Wisepill) and self-report. Discussion Behavioral interventions are greatly needed to improve ART adherence among HIV-infected adolescents and young adults and prevent onward transmission. If effective, the intervention tested here will be one of the first rigorously-designed efficacy trials to promote ART adherence in this population, using an approach that holds promise for being readily integrated into real-world clinical settings. Trial registration ClinicalTrials.gov number NCT03092531, registered March 28, 2017.

Abstract Background Although rates of severe HIV-associated neurocognitive disorders have declined in the post-antiretroviral treatment (ART) era, subtle deficits persist, possibly exacerbated by treatment non-adherence. The actual effects of ART interruption/initiation on brain glucose metabolism as a reflection of viral replication and neuroinflammation remain unclear. Our study investigates how treatment initiation and interruption alter brain glucose metabolism in SIV-infected macaques, using 18F-FDG PET in correlation with plasma and CSF viral loads (VL) and cytokine levels. Methods SIV-infected macaques (n = 7) underwent ART initiation only, ART interruption only, or both. Five uninfected animals served as controls. 18F-FDG PET imaging was performed at baseline and 1, 3, and 6 months after treatment modification. Mean and maximum standardized uptake values (SUV) for the whole-brain and subregions were calculated. Plasma and CSF VL and cytokine levels were measured. Paired t tests evaluated acute changes in whole-brain SUV from baseline to 1 month, while mixed-effect linear regression models evaluated changes over multiple timepoints and correlated SUV values with disease markers. Results ART interruption was associated with increased SUVmean and SUVmax acutely, after 1 month (SUVmean 95% CI [0.044–0.786 g/ml], p = 0.037; SUVmax 95% CI [0.122–3.167 g/ml], p = 0.041). The correlation between SUV and time, however, was not significant when evaluated across all timepoints. Increased SUVmean and SUVmax correlated with decreased CD4+ and CD8+ T-cell counts and increased plasma VL. SUVmax was positively associated with increases in CSF VL, and there were borderline positive associations between SUVmax and IL-2, and between SUVmean and IL-15. The treatment initiation group showed no associations between imaging and disease biomarkers despite viral suppression, reduced cytokine levels, and increased CD4+ and CD8+ T-cell counts. Conclusions ART interruption is associated with increased brain glucose metabolism within 1 month of treatment cessation, which, in concert with increased levels of pro-inflammatory cytokines in the CSF, may reflect neuroinflammation in the setting of viral rebound. Although we cannot assert neurologic damage in association with cerebral hypermetabolism, it is a concerning outcome of ART non-adherence. Treatment initiation, meanwhile, did not result in significant changes in brain metabolism. HIV-induced neuroinflammation may require a longer period to abate than our follow-up period allowed.

Abstract Background Condom use and antiretroviral therapy (ART) are effective means to prevent and control HIV transmission. We aimed to assess the effect of condom use in combination with antiretroviral therapy (ART) on HIV incidence and mortality among men who had sex with men (MSM) in Beijing, China. Methods We evaluated the effect of condom use, ART, and the combination of both among people living with HIV/AIDS (PLWHA) of MSM in the Chaoyang District of Beijing using the Asian Epidemic Model (AEM). Evaluation indicators included absolute risk reduction (ARR) and the percentage of relative risk reduction (RRR %). Results HIV incidence and prevalence declined substantially when condoms were used by MSM in Chaoyang from 2003 to 2013. The ARR of HIV incidence was from 0 to 0.91% and the RRR% was from 0 to 43.93%. The ARR of HIV prevalence was from 0 to 3.79% and the RRR% was from 0 to 31.53%. The HIV mortality rate decreased substantially (ARR from 0 to 1.75%, and RRR% from 0 to 40.03%) when ART was implemented. When condom use combined with ART was implemented in MSM in 2003–2013, HIV incidence declined substantially (ARR from 0 to 0.99%, and RRR% from 0 to 46.11%). HIV prevalence was also reduced with an ARR from 0 to 3.5%, and an RRR% from 0 to 29.88%. The HIV mortality also declined substantially (ARR from − 0.01% to 1.02%, RRR% from − 1.44% to 39.98%). Conclusions Among MSM, a combination of condom use and ART reduces both HIV incidence and mortality caused by HIV. Combining these methods results in a more effective prevention and control of HIV.

Abstract Characterizing HIV genetic diversity and evolution during antiretroviral therapy (ART) provides insights into the mechanisms that maintain the viral reservoir during ART. This review describes common methods used to obtain and analyze intra-patient HIV sequence data, the accumulation of diversity prior to ART and how it is affected by suppressive ART, the debate on viral replication and evolution in the presence of ART, HIV compartmentalization across various tissues, and mechanisms for the emergence of drug resistance. It also describes how CD4+ T cells that were likely infected with latent proviruses prior to initiating treatment can proliferate before and during ART, providing a renewable source of infected cells despite therapy. Some expanded cell clones carry intact and replication-competent proviruses with a small fraction of the clonal siblings being transcriptionally active and a source for residual viremia on ART. Such cells may also be the source for viral rebound after interrupting ART. The identical viral sequences observed for many years in both the plasma and infected cells of patients on long-term ART are likely due to the proliferation of infected cells both prior to and during treatment. Studies on HIV diversity may reveal targets that can be exploited in efforts to eradicate or control the infection without ART.

Abstract Background There is a growing concern for an increasing burden of non-communicable diseases (NCDs) in people living with HIV. This concern is evident especially in developing countries where dietary and lifestyle risk factors associated with NCDs are becoming more prominent. This study explored the prevalence of diabetes mellitus, hypertension, and hyperlipidemia and related risk factors in men and women living with HIV in Cambodia. Methods This cross-sectional study was conducted among 510 adult people living with HIV randomly selected from one city and four provinces in Cambodia. A structured questionnaire was used to collect data on socio-demographic characteristics, health behaviors, medical history, and antiretroviral therapy (ART). Anthropometric and biological measurements were performed. Descriptive statistics were used to calculate proportions and means of the measured variables. An independent Student’s t-test was used for continuous variables. Chi square test or Fisher’s exact test was used for categorical variables to explore gender differences. Results Prevalence of diabetes mellitus, hypertension, and hyperlipidemia was 9.4, 15.1, and 33.7%, respectively. The prevalence of hyperlipidemia was significantly higher among men compared to women. Mean systolic and diastolic blood pressures were also significantly higher among men. Regarding risk factors, 17.3% of participants were overweight, and 4.1% were obese. Tobacco and alcohol use was common, particularly among men. Fruit and vegetable consumption was considerably low among both men and women. Physical activity levels were also low. About 40% of participants reported having a job that involved mostly sitting or standing; 46.3% reported engaging in moderate activities; and 11.8% reported engaging in vigorous activities during leisure time. A significantly higher proportion of men compared to women engaged in vigorous activities both at work and during leisure time. Conclusions The prevalence of diabetes mellitus, hypertension, and hyperlipidemia among men and women living with HIV in Cambodia is considerably high. Related risk factors were also common. Given the comorbidity of NCDs and HIV, policy and programmatic interventions are required, including integration of NCD screening into HIV programs. Distinctions in the levels of diseases and in health behaviors between men and women suggest that interventions need to be tailor-made and gender-specific, targeting their respective diseases and behaviors.

Abstract Background In 2013, the World Health Organization released a new set of guidelines widely known as Option B+. Prior to that there were guidelines released in 2010. Option B+ recommends lifelong antiretroviral treatment for all pregnant and breastfeeding women living with Human Immunodeficiency Virus. The study aimed at investigating challenges and opportunities in implementing Infant and Young Child Feeding in the context of Prevention of Mother To Child Transmission (PMTCT) guidelines among HIV positive mothers of children aged 0–24 months. The study also examined implications presented by implementing the 2013 PMTCT consolidated guidelines in the transition phase from the 2010 approach in Zambia. Methods A mixed methods approach was employed in the descriptive cross sectional study utilizing semi structured questionnaires and Focused Group Discussions. Further, data was captured from the Health Information Management System. Results During the PMTCT transition, associated needs and challenges in institutionalizing the enhanced guidelines from option A and B to option B+ were observed. Nonetheless, there was a decline in Mother to Child Transmission (MTCT) of HIV rates with an average of 4%. Mothers faced challenges in complying with optimal breastfeeding practices owing to lack of community support systems and breast infections due to poor breast feeding occasioned by infants’ oral health challenges. Moreover, some mothers were hesitant of lifelong ARVs. Health workers faced programmatic and operational challenges such as compromised counseling services. Conclusion Despite the ambitious timelines for PMTCT transition, the need to inculcate new knowledge and vary known practice among mothers and the shift in counseling content for health workers, the consolidated guidelines for PMTCT proved effective. Some mothers were hesitant of lifelong ARVs, rationalizing the debated paradigm that prolonged chemotherapy/polypharmacy may be a future challenge in the success of ART in PMTCT. Conflicting breast feeding practices was a common observation across mothers thus underpinning the need to strongly invigorate Infant and Young Child Feeding information sharing across the continuum of heath care from facility level to community and up to the family; for cultural norms, practices and attitudes enshrined within communities play a vital role in child care.

Abstract Background Adolescents in South Africa are at high risk of acquiring HIV. The HIV vaccination of adolescents could reduce HIV incidence and mortality. The potential impact and cost-effectiveness of a national school-based HIV vaccination program among adolescents was determined. Method The national HIV disease and cost burden was compared with (intervention) and without HIV vaccination (comparator) given to school-going adolescents using a semi-Markov model. Life table analysis was conducted to determine the impact of the intervention on life expectancy. Model inputs included measures of disease and cost burden and hypothetical assumptions of vaccine characteristics. The base-case HIV vaccine modelled cost at US$ 12 per dose; vaccine efficacy of 50 %; duration of protection of 10 years achieved at a coverage rate of 60 % and required annual boosters. Incremental cost-effectiveness ratios (ICER) were calculated using life years gained (LYG) serving as the outcome measure. Sensitivity analyses were conducted on the vaccine characteristics to assess parameter uncertainty. Results The HIV vaccination model yielded an ICER of US$ 5 per LYG (95 % CI ZAR 2.77–11.61) compared with the comparator, which is considerably less than the national willingness-to-pay threshold of cost-effectiveness. This translated to an 11 % increase in per capita costs from US$ 80 to US$ 89. National implementation of this intervention could potentially result in an estimated cumulative gain of 23.6 million years of life (95 % CI 8.48–34.3 million years) among adolescents age 10–19 years that were vaccinated. The 10 year absolute risk reduction projected by vaccine implementation was 0.42 % for HIV incidence and 0.41 % for HIV mortality, with an increase in life expectancy noted across all age groups. The ICER was sensitive to the vaccine efficacy, coverage and vaccine pricing in the sensitivity analysis. Conclusions A national HIV vaccination program would be cost-effective and would avert new HIV infections and decrease the mortality and morbidity associated with HIV disease. Decision makers would have to discern how these findings, derived from local data and reflective of the South African epidemic, can be integrated into the national long term health planning should a HIV vaccine become available.