Antiretroviral Therapy Strategies Research Articles

Phylogenetic Network Analyses Reveal the Influence of Transmission Clustering on the Spread of HIV Drug Resistance in Quebec from 2002 to 2022.

HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced (n = 3500) and ART-naïve persons (n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- (n = 1577) and post-ART experience (n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2-5, vs. 6+ members per cluster as categorical variables. Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007-2011, 2012-2016, and 2017-2022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14-73 IQR) and 16 (9-26 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1-2%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-naïve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies/mL, respectively (p < 0.0001). Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR.

Treatment patterns and preferences of people living with HIV starting or switching antiretroviral therapy: Real-world evidence from Portugal.

There is a lack of up-to-date real-life evidence on antiretroviral therapy (ART) strategies among people living with HIV (PLWH) in Portugal. This study aimed to describe the treatment strategy used in PLWH either initiating or switching ART. Non-interventional, cross-sectional, multicenter study carried out between December 2019 and October 2021 in Portugal. A total of 237 PLWH were included in this study, 171 of whom were ART-experienced and 66 were ART-naïve. The study showed that triple regimens were the most common ART strategy and integrase strand transfer inhibitors-based therapy was the most frequently used therapeutic class in both ART-naïve and ART-experienced PLWH. Nevertheless, about a third of PLWH who started a triple regimen transitioned to a dual regimen. Patient-reported outcomes revealed high HIV literacy and similar ART preferences in both groups. This real-world study showed that triple regimens were the most widely used ART strategy, even after the European AIDS Clinical Society guidelines introduced the recommendation of a dual regimen for naïve patients. The cohorts of this study presented a high level of HIV literacy at the time of inclusion. Our findings highlighted that taking pills only once a day is considered a very important feature for most patients.

Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification Among Patients With Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-income Countries.

The World Health Organization recommends initiating same-day antiretroviral therapy (ART) while tuberculosis (TB) testing is under way for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve TB risk stratification in this population. In this baseline analysis of 498 adults (>18 years) with TB symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP as a continuous variable using generalized linear models. Eighty-seven (17.5%) participants were diagnosed with baseline TB. The median CRP was 33.0 mg/L (interquartile range: 5.1, 85.5) in those with TB, and 2.6 mg/L (interquartile range: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4% and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART and 0.8% to 5.0% would have untreated TB at ART initiation. CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3- to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.

Trends in HIV/AIDS-Related Mortality and the Impact of Antiretroviral Treatment Strategies in Lu'an City: A Comprehensive Analysis.

BACKGROUND There are many factors that affect human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-related deaths, and different antiretroviral therapy (ART) strategies may affect HIV/AIDS-related fatality rates. However, studies on this area are very limited. This study aimed to evaluate the factors associated with HIV/AIDS-related mortality and the impact of different ART strategies in Lu'an City, Anhui Province, China, 1999-2023. MATERIAL AND METHODS Data of HIV/AIDS cases were downloaded from the China HIV/AIDS Comprehensive Response Information Management System, and were assessed to evaluate the impact of different ART strategies on the related fatality rate using interrupted time series (ITS). RESULTS We found that age at diagnosis of 15 years, 25 years, 40 years, and 60 years, as well as receiving ART, were protective factors against death (with P below 0.05), while lower CD4 count at the last CD4 count and the year of diagnosis before 2007 and between 2007 and 2016 were risk factors (with P below 0.05). ITS analysis revealed that in the year of the introduction of free ART in 2006, the fatality rate decreased by 38.60% (P=0.015). The fatality rate trend from 2006 to 2015 was -1.1%, which was not statistically significant (P=0.434). The fatality rate trend from 2016 to 2023 was -0.33%, indicating a decreasing trend (P=0.000). CONCLUSIONS Children under 15 years old and elderly patients had a higher risk of death. The main reasons for the decrease in HIV/AIDS-related fatality rate were ART, especially the "early treatment" strategy.

Dolutegravir plus boosted darunavir versus recommended standard-of-care antiretroviral regimens in people with HIV-1 for whom recommended first-line non-nucleoside reverse transcriptase inhibitor therapy has failed (D2EFT): an open-label, randomised, phase 3b/4 trial

Randomised comparative data on efficacy and safety of second-line antiretroviral therapy (ART) after failure of non-nucleoside reverse transcriptase inhibitors (NNRTIs) across diverse geographical settings are scarce. The aim of this study was to evaluate optimal second-line ART for people with HIV. D2EFT is a completed international, randomised, open-label, phase 3b/4 trial evaluating three second-line ART strategies in adults (aged ≥18 years) with HIV-1 for whom first-line NNRTI therapy has failed. The study was done at 28 sites across 14 countries in Asia, Africa, and Latin America. It was originally designed to compare recommended standard of care (ritonavir-boosted darunavir [800 mg darunavir plus 100 mg ritonavir once daily] plus two nucleoside reverse transcriptase inhibitors [NRTIs; dosed once or twice daily]) with a novel nucleoside sparing regimen of dolutegravir (50 mg once daily) with ritonavir-boosted darunavir. The study was adapted during the first year to add a third arm of dolutegravir (50 mg once daily) with fixed tenofovir disoproxil fumarate (300 mg once daily) plus either lamivudine (300 mg once daily) or emtricitabine (200 mg once daily). Participants were randomly assigned with a computer-generated, blocked randomisation scheme (block size of two) stratified by site, previous tenofovir disoproxil fumarate use, and HIV viral load. The trial was designed to evaluate non-inferiority of either interventional arm against standard of care for the primary outcome of virological suppression, as determined by HIV RNA load of less than 50 copies per mL at 48 weeks. The prespecified non-inferiority margin was 12%. Comparisons were made with a modified intention-to-treat population, including all participants randomly assigned but excluding administrative withdrawals. This study is registered with ClinicalTrials.gov, NCT03017872. 1190 individuals were screened; 828 participants were enrolled between Nov 1, 2017, and Dec 31, 2021. Two participants were unable to receive their assigned regimen for administrative reasons; and 826 participants were included in analyses. Median age was 39 years (IQR 33-46), and 450 (54%) participants were female. Baseline median CD4 count was 206 cells per μL (23-354) and median HIV RNA was 15 400 copies per mL (3600-65 986). The proportion of participants with HIV RNA of less than 50 copies per mL at 48 weeks was 194 (75%) of 257 in the ritonavir-boosted darunavir plus two NRTIs group, 222 (84%) of 264 in the ritonavir-boosted darunavir plus dolutegravir group, and 227 (78%) of 291 in the dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine group. Compared with ritonavir-boosted darunavir plus two NRTIs, the difference in virological suppression was 8·6% (95% CI 1·7 to 15·5; p=0·016) for dolutegravir plus ritonavir-boosted darunavir and 6·7% (-1·2 to 14·4; p=0·093) for dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine. Six deaths occurred, none of which were related to treatment. 19 pregnancies (11 livebirths) occurred with no congenital defects. In individuals experiencing failure of an NNRTI-based first-line ART, a switch to either dolutegravir plus ritonavir-boosted darunavir or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine, without universal access to genotyping, was non-inferior in achieving viral suppression compared with ritonavir-boosted darunavir plus two NRTIs. These global data support the most recent WHO treatment guidelines. UNITAID; National Institute of Allergy and Infectious Diseases, USA; National Health and Medical Research Council, Australia; ViiV Healthcare; and Janssen.

Challenges and commonly used countermeasures in the implementation of lifelong antiretroviral therapy for PMTCT in Central Uganda: Health providers' perspective.

Uganda has implemented lifelong antiretroviral therapy for the prevention of mother-to-child HIV transmission since September 2012. Implementation of this strategy has been met with health provider and client challenges which have persisted up to date. This study explored providers' perspectives on the challenges and countermeasures of the implementation and scale-up of lifelong ART among pregnant and breastfeeding women. A qualitative descriptive study was conducted whereby 54 purposively selected participants from six facilities in three districts of Central Uganda namely; Masaka, Mityana, and Luwero were recruited. A key informant interview guide was used to collect data from the study participants. The data were thematically analysed using Atlas-ti, Version 7. Study participants reported challenges under the themes of 1) inadequacy of HIV service delivery (lack of relevant training, health provider shortages, inadequate counselling, stock-outs of essential HIV commodities); 2) Non-utilization of HIV services (Non-disclosure of HIV- positive results, denial of HIV positive results, fear to be followed up, unwillingness to be referred, large catchment area, lack of transport); and 3) Suboptimal treatment adherence (fear of ART side effects, preference for traditional medicines, low male partner involvement in care and treatment). Strategies such as on-job training, mentorship, task shifting, redistribution of HIV commodities across facilities, accompanying of women to mother-baby care points, ongoing counseling of women, peers, and family support groups were commonly used countermeasures. This study highlights key challenges that health providers face in implementing lifelong antiretroviral therapy services among pregnant and postpartum women. Context-specific, innovative, and multilevel system interventions are required at national, district, health facility, community and individual levels to scale up and sustain the lifelong antiretroviral therapy strategy among pregnant and breastfeeding women.

Predictors of virologic outcome among people living with HIV who continue a protease inhibitor-based antiretroviral regimen following virologic failure with no or limited resistance

BackgroundTreatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression.MethodsA5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up).Results56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mm3, HIV-1 RNA 20,444 copies/mL; and 37% had NRTI resistance. The estimated proportion experiencing VF increased from 39% at week 24 to 60% at week 96. In multivariable analysis, significant predictors at study entry of VF were higher HIV-1 RNA (adjusted hazard ratio: 2.20 for ≥ 10,000 versus < 10,000 copies/mL), lower age (1.96 for < 30 versus ≥ 30 years), NRTI resistance (1.74 for present versus absent), lower CD4 count (1.73 for < 200 versus ≥ 200 cells/mm3), and shorter ART duration (1.62 for < 10 versus ≥ 10 years). There was a strong trend in proportion with VF at week 96 with the number of these five risk factors that a participant had, varying from 8% for zero, to 31%, 40%, 73%, and 100% for one, two, three, and four/five. Only 13% of participants developed new NRTI or PI resistance mutations.ConclusionA simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.

Changing Mortality and Patterns of Death Causes in HIV Infected Patients - China, 2013-2022.

The advent of antiretroviral therapy (ART) has markedly decreased mortality rates among patients infected with human immunodeficiency virus (HIV). Globally, there has been a 43% reduction in acquired immunodeficiency syndrome (AIDS)-related deaths from 2010 to 2022. Additionally, prior research indicates that the initiation of ART at an early stage within China has substantially lowered mortality rates. Over the previous decade, following the implementation of China's universal ART access strategy, the patterns of mortality causes among HIV-infected individuals across the country have undergone significant alterations. In 2022, the all-cause mortality rate among this population was reported at 2.7%, with the non-AIDS-related mortality rate at 1.8%. However, it is important to consider that the accuracy of death reporting could contribute to potential misclassification of the underlying causes of death. Efforts to enhance health outcomes should persist in emphasizing the advancement of ART strategies, with a particular focus on mitigating non-AIDS-related mortality in the future.

HIV treatment strategies across Central, Eastern and Southeastern Europe: New times, old problems.

In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines. The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region. In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons. In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries.

Adaption of an ongoing clinical trial to quickly respond to gaps in changing international recommendations: the experience of D2EFT

A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART.

Threshold dynamics of a nonlocal dispersal HIV/AIDS epidemic model with spatial heterogeneity and antiretroviral therapy

Antiretroviral therapy and long-range diffusion of HIV-infected individuals in heterogeneous environments can greatly impact the transmission and distribution of HIV/AIDS in a population. In this paper, we present a nonlocal dispersal HIV/AIDS epidemic model incorporating spatial heterogeneity as well as antiretroviral therapy to study the spatial and temporal dynamics of HIV/AIDS in China. To overcome the difficulty about a lack of compactness of the semiflow and the challenge about the existence and uniqueness of the principal eigenvalue of an eigenvalue problem without obvious compactness, we apply the operator semigroup and dissipative system theories. We establish the well-posedness and the existence of the global attractor for the system. Then we derive the basic reproduction number R0 which is defined as the spectral radius of the next generation operator by the renewal equation. Afterwards, we obtain the global dynamics of the system in terms of R0. Our numerical simulations suggest that: (1) the dynamics of HIV/AIDS transmission largely depends on the nonlocal dispersal kernel function; (2) it is necessary to monitor and design/refine rules for the mobility of HIV-infected population between remote and metropolitan areas to control the HIV/AIDS transmission; (3) antiretroviral therapy benefits not only each treated individual but also the entire community, and increasing the therapy coverage rate is one of the most effective ways to prolong the longevity of HIV-infected population. Moreover, spatial dispersal is also an important factor that cannot be ignored for designing antiretroviral therapy strategies.

Adherence barriers and interventions to improve ART adherence in Sub-Saharan African countries: A systematic review protocol.

The HIV/AIDS pandemic continues to be a major public health concern, particularly in Sub-Saharan Africa (SSA). Despite efforts to reduce new infections and deaths with the use of antiretroviral therapy (ART), SSA countries continue to bear the heaviest burden of HIV/AIDS globally, accounting for two-thirds of global new infections. The goal of this review is to identify common barriers to ART adherence as well as common effective interventions that can be implemented across SSA countries to improve ART adherence. A systematic review of published studies on adult HIV-positive patients aged 15 or above, that have assessed the barriers to ART adherence and interventions improving patients' adherence to ART in SSA countries shall be conducted. We will conduct electronic searches for articles that have been published starting from January 2010 onwards. The databases that shall be searched will include Medline Ovid, CINAHL, Embase, and Scopus. The review will include experimental and quasi-experimental studies such as randomized and non-randomized controlled trials as well as comparative before and after studies, and observational studies-cross-sectional studies, cohort studies, prospective and retrospective studies. Two independent reviewers will screen all identified studies, extract data and appraise the methodological quality of the studies using standard critical appraisal tools from the Joanna Briggs Institute. The extracted data will be subjected to a meta-analysis and narrative synthesis. This review will synthesize existing evidence on ART adherence barriers and strategies for improving patient adherence to ART in SSA countries. It will identify common barriers to adherence and common interventions proven to improve adherence across SSA. We anticipate that the findings of this review will provide information policy makers and stakeholders involved in the fight against HIV, will find useful in deriving better ways of not only retaining patients on treatment but having them adhere to their treatment. This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42021262256.

Dynamic analysis of mother-to-child transmission of HIV and antiretroviral treatment as optimal control

Human immunodeficiency virus (HIV) is still an extremely dangerous pandemic and without a prominent cure. And one of the most vulnerable population prone to acquiring the virus can be newborn babies from their HIV positive mothers. It can even turn fatal when an individual gets acquired immunodeficiency syndrome (AIDS) and the disease is left untreated and uncontrolled. One such treatment for suppressing the infections is antiretroviral therapy (ART) treatment. To gain insight of the Indian scenario of the mother to child transmission (MTCT) and the present work of the ARTs strategy in India we shall study a model for HIV infected newborns. Hence, we have formulated a model consisting of newborns born to HIV infected mothers, infected newborns and newborns acquiring AIDS. We have found the equilibrium points and established the local stability of the system. We then considered ARTS as optimal control for the HIV infected newborns and thus, extended our model with the class of newborns going for ARTS. With the help of Pontryagin’s Maximum Principle, we then obtain the optimal ART intensity as part of intervention to control infection among newborns for our optimal control problem. For the numerical simulations we took real time data of India for all parameters along with MTCT rate for the state of Maharashtra. One of our numerical results shows that ART’s as strategy among newborns born to HIV infected mothers decreases the number of HIV infected babies. Thus, the paper highlights the necessary and crucial role of ART programs for babies born to HIV positive mothers in order to suppress the infection for their brighter futures in the epidemic dynamics of India.

Risk for Non-AIDS-Defining and AIDS-Defining Cancer of Early Versus Delayed Initiation of Antiretroviral Therapy : A Multinational Prospective Cohort Study.

Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500×109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. To estimate the long-term risk difference for cancer with the immediate ART strategy. Multinational prospective cohort study. The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts <350 and <500×109 cells/L) ART initiation strategies. During 64021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500×109 cells/L and less than 350×109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Potential residual confounding due to observational study design. In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Highly Active Antiretroviral Therapy Oversight Committee.

Influencing factors of antiretroviral therapy and its association with immunological effect among HIV/AIDS patients in Taizhou city, 2006-2019

Objective: To analyze influencing factors of instant antiretroviral therapy (ART) and explore associution between strategies of ART and immunological effects among HIV/AIDS patients in Taizhou city during 2006-2019. Methods: A retrospective cohort study was conducted on HIV/AIDS patients under ART, and a logistic regression model was used to analyze factors of instant ART. The student t-test and chi-square test were used to compare immunological effect of different ART strategies while the Kaplan-Meier method was used to generate a survival curve. Results: A total of 2 971 HIV/AIDS patients were enrolled with 1 786 cases (60.1%) having instant ART strategy. The proportion of instant ART were 77.8% (1 170/1 504) during 2016 to 2019. The treatment success rate of the instant ART group (87.4%, 1 561/1 786) were higher than the delayed ART group (84.4%, 1 000/1 185). The results of multivariate logistic regression model indicated that male (aOR=1.28, 95%CI: 1.03-1.59), married (aOR=1.71, 95%CI: 1.33-2.19) and baseline CD(4)(+)T lymphocyte cells (CD(4)) counts ≤200 cells/μl (aOR=1.60, 95%CI: 1.27-2.02) were factors positively related to instant ART while 31-40 years old (aOR=0.63, 95%CI: 0.48-0.84), infected through heterosexual transmission(aOR=0.60, 95%CI: 0.49-0.74) and diagnosed before 2015 (aOR=0.20, 95%CI: 0.17-0.23) were inversely related to instant ART. The increase of the CD(4)/CD(8) ratio was greater, and the cumulative ART success rate was higher each year in the instant ART group than in the delayed ART group (P<0.05). Conclusions: The instant ART strategy has been well implemented in Taizhou city during 2006-2019, and the immunological effect was better in instant ART group. The proportion of instant ART were more than 60.0% among HIV/AIDS patients. Instant ART strategy needs to be strengthened for those who are 31-40 years old, women, unmarried, and infected through heterosexual transmission in an attempt to further increase treatment level and improve treatment effect.

Adherence to recommendations for ART and targeted PrEP use among HIV serodiscordant couples in East Africa: the \u201cPrEP as a bridge to ART\u201d strategy

BackgroundPrEP use should be aligned with periods of risk for HIV acquisition. For HIV serodiscordant couples, PrEP can be used as a bridge until the partner living with HIV takes antiretroviral therapy (ART) long enough to achieve viral suppression (the “PrEP as a Bridge to ART” strategy). However, adherence to this strategy is unknown.MethodsIn a demonstration project in Kenya and Uganda, HIV-uninfected partners of serodiscordant couples were advised to take PrEP until the partner living with HIV took ART for ≥ 6 months. PrEP discontinuation was then recommended unless there were concerns about ART adherence, immediate fertility intentions, or outside partners with unknown HIV/ART status. Electronic adherence monitoring and socio-behavioral questionnaire data were used in logistic regression models to explore completion of this strategy and continuation of PrEP beyond recommendations to stop its use.ResultsAmong 833 serodiscordant couples, 436 (52%) HIV-uninfected partners completed ≥ 6 months of PrEP as a bridge to ART. Strategy completion was associated with older age (aOR per 5 years = 1.1; p = 0.008) and having fewer children (aOR = 0.9; p = 0.019). Of the 230 participants encouraged to stop PrEP according to strategy recommendations, 170 (74%) did so. PrEP continuation among the remaining 60 participants was associated with more education (aOR = 1.1; p = 0.029), a preference for PrEP over ART (aOR = 3.6; p = 0.026), comfort with managing their serodiscordant relationship (aOR = 0.6; p = 0.046), and believing PrEP makes sex safe (aOR = 0.5; p = 0.026).ConclusionHalf of participants completed the PrEP as a bridge to ART strategy and the majority stopped PrEP as recommended. These findings suggest that targeting PrEP to periods of risk is a promising approach; however, tailoring counseling around aligning PrEP use and HIV risk will be important for optimal strategy implementation.

Cost of Human Immunodeficiency Virus (HIV) and Determinants of Healthcare Costs in HIV-Infected Treatment-Naive Patients Initiated on Antiretroviral Therapy in Germany: Experiences of the PROPHET Study

The purpose of the prospective clinical and pharmacoeconomic outcomes study of different first-line antiretroviral treatment strategies (PROPHET) was to examine the healthcare costs of human immunodeficiency virus (HIV)-infected persons in Germany treated with different antiretroviral therapy (ART) strategies and to identify variables associated with high costs. The setting was a 24-month prospective multicenter observational cohort study in a German HIV-specialized care setting from 2014 to 2017. A microcosting approach was used for the estimation of healthcare costs. Data were obtained via electronic case report forms. The costs were calculated from both the societal and the statutory health insurance perspective. Regression models were performed that took into consideration the impact of several independent variables. Four hundred thirty-four patients from 24 centers throughout Germany were included. Average annual healthcare costs were €20 118 (standard deviation [SD] €6451) per patient from the societal perspective (n= 336) and €17 306 (SD €4106) from the statutory health insurance perspective (n= 292). Expenditures for the ART medication had the highest impact. Total costs declined in the second year of therapy. There was a significant association between the amount of total cost and clinical or therapeutic variables from both perspectives; a diagnosis of acquired immune deficiency syndrome (AIDS) led to higher costs as well as the chosen ART strategy. Age also increased cost from the statutory health insurance perspective. The main cost driver of the healthcare costs for HIV-positive patients was antiretroviral drug expenses. Further variables that influenced the costs were identified. The results provide a detailed overview of the resource use of patients in the PROPHET cohort.

Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study

Allogeneic blood or marrow transplantation (alloBMT) is a potentially life-saving treatment for individuals with HIV and haematological malignancies; challenges include identifying donors and maintaining antiretroviral therapy (ART). The objectives of our study were to investigate interventions to expand donor options and to prevent ART interruptions for patients with HIV in need of alloBMT. This single-arm, interventional trial took place at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD, USA). Individuals with HIV who were at least 18 years of age and referred for alloBMT for a standard clinical indication were eligible. The only exclusion criterion was a history of documented resistance to enfuvirtide. We used post-transplant cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis to expand donor options and an optimised ART strategy of avoiding pharmacoenhancers and adding subcutaneous enfuvirtide during post-transplant cyclophosphamide and during oral medication intolerance. Our primary outcome was the proportion of participants who maintained ART through day 60 after alloBMT. We measured the HIV latent reservoir using a quantitative viral outgrowth assay. This study is registered on ClinicalTrials.gov, NCT01836068. Between June 1, 2013, and August 27, 2015, nine patients who were referred for transplant provided consent. Two patients had relapsed malignancy before donor searches were initiated. Seven patients had suitable donors identified (two matched sibling, two matched unrelated, two haploidentical, and one single-antigen mismatched unrelated) and proceeded to alloBMT. All patients maintained ART through day 60 and required ART changes (median 1, range 1-3) in the first 90 days. One patient stopped ART and developed HIV rebound with grade 4 meningoencephalitis at day 146. Among six patients who underwent alloBMT and had longitudinal measurements available, the HIV latent reservoir was not detected post-alloBMT in four patients with more than 95% donor chimerism, consistent with a 2·06-2·54 log10 reduction in the HIV latent reservoir. In the two patients with less than 95% donor chimerism, the HIV latent reservoir remained stable. By using post-transplant cyclophosphamide as GVHD prophylaxis, we successfully expanded alloBMT donor options for patients with HIV. Continuing ART with a regimen that includes enfuvirtide post-alloBMT was safe, but life-threatening viral rebound can occur with ART interruption. amfAR (the Foundation for AIDS Research), Johns Hopkins University Center for AIDS Research, and National Cancer Institute.

Prevalence, determinants, and impact of suboptimal adherence to HIV medication in 25 countries

Modern antiretroviral therapy (ART) has improved the lives of people living with HIV (PLHIV) but currently requires daily adherence. We assessed prevalence and correlates of suboptimal adherence, and measured associations with self-reported health outcomes. Data were from web-based surveys of confirmed HIV+ adults on antiretroviral treatment within 25 countries during 2019 (n = 2389). Suboptimal adherence was a report of ≥1 reason for missing ART ≥5 times within the past month. Multivariable logistic regression examined associations between suboptimal adherence and self-reported overall health and virologic suppression. Overall, 24.1% (575/2389) reported suboptimal adherence, from 10.0% (5/50) in Austria, to 62.0% (31/50) in China. The most common reasons for missing ART ≥5 times in the overall population were feeling depressed/overwhelmed (7.4%, 176/2389), trying to forget about HIV (7.0%, 168/2389), and work (6.1%, 145/2389). Correlates of suboptimal adherence included being heterosexual, <50 years old, ≤high school, having gastrointestinal treatment side effects, and privacy concerns. Odds of suboptimal overall health were 1.41 (95%CI, 1.11–1.80), 2.10 (95%CI, 1.65–2.68), and 2.55 (95%CI, 2.00–3.25) among those who reported the maximum number of times missed ART for any reason within the past month as 1, 2–4, or ≥5 times respectively, vs not missing at all. Odds of virologic nonsuppression were 1.80 (95%CI, 1.33–2.45), and 2.24 (95%CI, 1.66–3.02) for 2–4, or ≥5 times of missed ART respectively, vs not missing at all; missing for only 1 time was not significantly associated with virologic nonsuppression. Novel ART strategies designed to improve adherence along with interventions to empower PLHIV and support self-medication may improve health outcomes and quality of life.

Perceptions of HIV Virologic Control Strategies Among Younger and Older Age Groups of People Living with HIV in the United States: A Cross-Sectional Survey.

Two HIV virologic control advances are in various stages of development, including long-acting antiretroviral therapy (ART) formulations and strategies aimed at sustained ART-free HIV control. Perceptions of risks and benefits toward HIV virologic control strategies may be different based on an individual's age due to differing experiences of the impacts of the domestic HIV epidemic, altruistic attitudes toward research participation, and general levels of engagement in health care. We examined preferences of HIV virologic control strategies by age groups. In 2018, we conducted a nationwide, online cross-sectional survey to examine differences in HIV virologic control strategies among a sample of people living with HIV who were <50 and ≥50 years of age. From a total of 281 participants, 3 findings were noteworthy: (1) Participants <50 years of age were more likely to be demotivated by perceived social risks (e.g., stigma, discrimination, HIV disclosure, and fear of transmitting HIV during a treatment interruption), compared with those ≥50 years; (2) participants ≥50 years of age were more motivated by altruistic notions compared with those <50 years; and (3) we noted greater desirability of longer long-acting ART and new HIV cure-related strategies among participants <50 years versus those ≥50 years. Our analysis provides a deeper understanding of differences in perceptions among various age groups regarding desirable future ART characteristics, and motivations and barriers to participating in HIV cure-related strategies. Our findings can help inform community engagement and education, and assist researchers in tailoring study design and recruitment efforts to major age groups.