Years Of Antiretroviral Therapy Research Articles

Assessment of Metabolic, Inflammatory, and Immunological Disorders Using a New Panel of Plasma Parameters in People Living with HIV Undergoing Antiretroviral Therapy-A Retrospective Study.

Background/Objectives: People living with HIV (PLWH) treated with combined antiretroviral therapy (cART) show a greater predisposition to metabolic and inflammatory disturbances compared to the general population. This study aimed to assess the effect of five years of cART use on the level of selected parameters related to carbohydrate and lipid metabolism and inflammation in PLWH compared to the uninfected. Methods: The levels of sirtuins (-1, -3, -6); irisin (IRS); myostatin (MSTN); peptide YY (PYY); glucagon-like peptide-1 (GLP-1); dipeptidyl peptidase IV (DPP-4); fetuin-A (FETU-A); pentraxin 3 (PTX3); chemokine stromal cell-derived factor 1 (SDF-1); regulated on activation, normal T cell expressed and presumably secreted (RANTES); and interleukins (-4, -7, -15) in the plasma of PLWH and a control group were evaluated by immunoassay methods. The results obtained after five years of antiretroviral therapy were compared with the levels obtained before and one year after cART. Results: Analysis of the parameters after five years of cART showed significantly higher levels in PLWH compared to the control group for SIRT-6, IRS, and IL-4 and significantly lower levels for RANTES and IL-7. There were significantly higher levels of SIRT-6, PYY, GLP-1, and PTX3 obtained after five years of cART compared to the results before therapy and after one year of cART. Conclusions: The results indicated changes occur in the expression of selected parameters during cART use in PLWH. Further research on the clinical usefulness of selected parameters and obtaining new information on the development of HIV-related comorbidities needs to be conducted.

Sociodemographic and Clinical Predictors of Weight Gain During the First Year of Antiretroviral Therapy among Adults Living With HIV in Urban Tanzania.

Antiretroviral therapy (ART) has improved the survival of people living with HIV (PLHIV) but this success has been accompanied by an increase in noncommunicable diseases. We conducted a prospective cohort study of 4000 adult PLHIV who were initiating ART in Dar es Salaam, Tanzania, to assess weight gain during the first year of treatment and associated sociodemographic and clinical factors. Anthropometric data were collected at ART initiation and monthly follow-up visits. The mean weight gain during the first year of treatment was 2.6 ± 0.3 kg, and the prevalence of overweight or obesity increased from 26.3% at baseline to 40.7%. Female sex, greater household wealth, lower CD4-T-cell counts, higher WHO HIV disease stage, and pulmonary tuberculosis were associated with a greater increase in body mass index (P < .05). Weight gain following ART initiation was common but was greater among females and PLHIV with advanced HIV or comorbidities.

P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV.

The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10-20 cells). Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03-9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03-2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01-2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24-0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76-2.40). In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up.

Impact of pretreatment low-abundance HIV-1 drug resistance on virological failure after 1 year of antiretroviral therapy in China.

To assess the impact of pretreatment low-abundance HIV drug-resistant variants (LA-DRVs) on virological outcomes among ART-naive HIV-1-infected Chinese people who initiated ART. A nested case-control study was conducted among HIV-1-infected individuals who had pretreatment drug resistance (PDR) genotypic results. Cases were defined as individuals with virological failure (HIV-1 RNA viral load ≥1000 copies/mL) after 1 year of ART, and controls were individuals from the same cohort whose viral load was less than 1000 copies/mL. Next-generation sequencing was used to identify low-abundance PDR mutations at detection thresholds of 10%, 2% and 1%. The mutant load was calculated by multiplying the abundance of HIV-1 drug-resistant variants by the pretreatment viral load. The impact of pretreatment low-abundance mutations on virological failure was estimated in logistic regression models. Participants (43 cases and 100 controls) were included in this study for the analysis. The proportion of participants with PDR was higher in cases than in controls at different detection thresholds (44.2% versus 22.0%, P = 0.007 at 10% threshold; 58.1% versus 31.0%, P = 0.002 at 2% threshold; 90.7% versus 69.0%, P = 0.006 at 1% threshold). Compared with participants without PDR, participants with ≥10% detectable PDR mutations were associated with an increased risk of virological failure (adjusted OR 8.0, 95% CI 2.4-26.3, P = 0.001). Besides this, individuals with pretreatment LA-DRVs (2%-9% abundance range) had 5-fold higher odds of virological failure (adjusted OR 5.0, 95% CI 1.3-19.6, P = 0.021). Furthermore, LA-DRVs at 2%-9% abundance resistant to NRTIs and mutants with abundance of ≥10% resistant to NNRTIs had a 4-fold and 8-fold risk of experiencing virological failure, respectively. It was also found that a mutant load of more than 1000 copies/mL was predictive of virological failure (adjusted OR 7.2, 95% CI 2.5-21.1, P = 0.0003). Low-abundance PDR mutations ranging from 2% to 9% of abundance can increase the risk of virological failure. Further studies are warranted to define a clinically relevant threshold of LA-DRVs and the role of NRTI LA-DRVs.

Brief Report: Changes in Nocturnal Heart Rate Variability in People Living With HIV During the First Year of Antiretroviral Therapy Compared With HIV-Uninfected Community Controls.

Higher nocturnal heart rate and lower nocturnal heart rate variability (HRV) is associated with increased cardiovascular disease mortality. Longitudinal studies on nocturnal HRV in people living with HIV (PLWH) are lacking. We conducted a 1-year prospective cohort study of adult PLWH and HIV-uninfected community controls in northwestern Tanzania. At enrollment, we collected data on cardiovascular risk factors and tested blood samples for hemoglobin, insulin, CD4 cell count, and C-reactive protein. We measured nocturnal HRV and heart rate at baseline and first-year follow-up. Mixed effect linear regression was used to determine predictors of lower HRV. Of the 111 enrolled participants (74 PLWH and 37 HIV-uninfected adults), 57.7% were female and the median age was 40 years. Over 1 year of follow-up, the average nocturnal heart rate was 4.5 beats/minute higher in PLWH ( P = 0.006). In the fully adjusted model (with age, sex, nocturnal heart rate, and diabetes), average nocturnal HRV was 10.5 milliseconds lower in PLWH compared with HIV-uninfected adults ( P = 0.03). Unlike with nocturnal heart rate, nocturnal HRV did not improve after 1 year of ART in PLWH or HIV-uninfected adults (fully adjusted change = -2.5 milliseconds, P = 0.45). Lower educational attainment, lesser pancreatic β-cell function, and anemia were associated with higher HRV. Nocturnal parasympathetic nervous system function was persistently lower in PLWH compared with HIV-uninfected adults even after antiretroviral therapy initiation. Improving nocturnal autonomic nervous system function could be a target for cardiovascular disease prevention in PLWH.

Adoption is not associated with immunological and virological outcomes in children with perinatally acquired HIV infection in the Netherlands.

To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children's adoption status. A prospective population-based open cohort including children with PHIV in NL. We included children with PHIV who had entered HIV care in NL since 2007, in view of a sharp increase in the number of adopted children with PHIV since that year. We compared the proportion with virologic suppression and CD4+T-cell count over time between the following groups of children with PHIV: adopted and born outside NL, non-adopted born in NL, and non-adopted born outside NL, using generalized estimating equations and linear mixed effects models, respectively. To account for the variation in cohort inclusion, we analyzed data of children exposed to at least one year of antiretroviral therapy (ART). We included 148 children (827.5 person-years of follow-up, 72% adopted, age at start care in NL 2.4 (0.5-5.3)). Under-18 mortality was zero. Over the years, a boosted PI-based regimen was most often prescribed. The use of integrase inhibitors increased since 2015. Non-adopted children born in NL were less likely to achieve virological suppression compared to adopted children (OR 0.66, 95%CI 0.51-0.86, p = 0.001), which disappeared after excluding one child with suspected treatment nonadherence (OR 0.85, 95%CI 0.57-1.25, p = 0.400). CD4+T-cell Z-score trajectories were not significantly different between groups. Despite considerable and increasing diversity of the population of children with PHIV in NL, geographical origin and adoption status do not seem to pose important challenges in achieving good immunological and virological outcomes.

Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants

The decay kinetics of HIV-1-infected cells are critical to understand virus persistence. We evaluated the frequency of simian immunodeficiency virus (SIV)-infected cells for 4 years of antiretroviral therapy (ART). The intact proviral DNA assay (IPDA) and an assay for hypermutated proviruses revealed short- and long-term infected cell dynamics in macaques starting ART ∼1 year after infection. Intact SIV genomes in circulating CD4+T cells showed triphasic decay with an initial phase slower than the decay of the plasma virus, a second phase faster than the second phase decay of intact HIV-1, and a stable third phase reached after 1.6-2.9 years. Hypermutated proviruses showed bi- or mono-phasic decay, reflecting different selective pressures. Viruses replicating at ART initiation had mutations conferring antibody escape. With time on ART, viruses with fewer mutations became more prominent, reflecting decay of variants replicating at ART initiation. Collectively, these findings confirm ART efficacy and indicate that cells enter the reservoir throughout untreated infection.

Iron status among HIV-infected adults during the first year of antiretroviral therapy in Tanzania.

The influence of inflammation on iron status among people living with HIV (PLWHIV) has not been well explored. We evaluated the trajectory of iron status among PLWHIV during the first year of highly active antiretroviral therapy (HAART), compared alternative approaches for inflammation correction, and assessed the associations of iron status with HIV-1 viral load and anthropometric outcomes. We conducted a secondary analysis of data from a randomized trial among 400 adults initiating HAART in Tanzania. Ferritin and C-reactive protein (CRP) were measured at baseline, 1, 6 or 12 months. Ferritin was considered in four ways: unadjusted, and adjusted for inflammation using higher cut-off (HC), Thurnham-corrected (TC) and regression-corrected (RC) approaches. For unadjusted, TC and RC ferritin, iron deficiency (ID) was defined using ferritin < 15 μg/L and elevated iron status was defined using ferritin > 150 μg/L among females and > 200 μg/L among males. For HC ferritin, elevated iron status was defined based on serum ferritin > 500 μg/L, while ID was defined using ferritin < 70 μg/L in the presence of inflammation and < 15 μg/L in the absence of inflammation. Regression models evaluated the trajectory of ferritin concentration across categories of baseline characteristics, and assessed the association of iron status with viral and anthropometric outcomes. The prevalence of iron deficiency at HAART initiation was 9% for unadjusted, 17% for HC, 12% for TC and 22% for RC ferritin. The prevalence of elevated iron status was 42% for unadjusted, 18% for HC, 31% for TC, and 15% for RC ferritin. The prevalence of iron deficiency for all three methods increased during the first year of HAART, while the prevalence of elevated iron status decreased. Baseline elevated iron status defined using HC ferritin was associated with a greater risk of HIV-1 viral load > 1000 copies/mL [relative risk (RR)= 4.29, 95% CI: 1.38-13.3] and incidence of being underweight [body mass index (BMI) < 18.5kg/m2 , hazard ratio (HR)= 3.65, 95% confidence interval (CI): 1.38-9.67]. Neither baseline-elevated iron status defined using TC or RC ferritin nor baseline iron deficiency defined using any of the three methods was associated with HIV-1 viral load or anthropometric outcomes. Whether and how inflammation correction is done influences findings of studies of iron status among PLWHIV.

A "Return to Health" Is Associated With Blood Pressure Increase After a Year of Antiretroviral Therapy in People With HIV.

Journal Article A “Return to Health” Is Associated With Blood Pressure Increase After a Year of Antiretroviral Therapy in People With HIV Get access Sepiso K Masenga, Sepiso K Masenga HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia Correspondence: Sepiso K. Masenga (smasenga@mu.ac.zm or sepisomasenga@gmail.com). https://orcid.org/0000-0003-4376-5831 Search for other works by this author on: Oxford Academic PubMed Google Scholar Joreen P Povia, Joreen P Povia HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia Search for other works by this author on: Oxford Academic PubMed Google Scholar Mboozi E Choonga, Mboozi E Choonga HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia Search for other works by this author on: Oxford Academic PubMed Google Scholar Benson M Hamooya Benson M Hamooya HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Hypertension, Volume 35, Issue 11, November 2022, Pages 915–917, https://doi.org/10.1093/ajh/hpac094 Published: 12 August 2022 Article history Received: 29 July 2022 Accepted: 09 August 2022 Published: 12 August 2022 Corrected and typeset: 31 August 2022

Blood Pressure and Body Composition During First Year of Antiretroviral Therapy in People With HIV Compared With HIV-Uninfected Community Controls.

Body composition changes may explain the rapid increase in blood pressure (BP) in people with HIV (PWH) during the first year of antiretroviral therapy. We analyzed data from a cohort of PWH and HIV-uninfected adults from the same communities in Mwanza, Tanzania. Blood pressure (BP, mm Hg) and body composition data were collected at baseline and 12-month follow-up. We used multivariable linear regression to compare BP changes in PWH and HIV-uninfected adults, and the relationship between changes in body composition and changes in BP. BP data were available for 640 PWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PWH, systolic BP (SBP) increased (114-118) whereas SBP decreased (125-123) in HIV-uninfected participants. Fat mass increased by 1.6 kg on average in PWH and was strongly associated with the change in BP (P < 0.001). The greater increase in SBP in PWH was partly explained by the lower baseline SBP but PWH still experienced a 2.2 (95% CI: 0.3-4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PWH; a 1-kg increase in fat mass accounted for 0.8 (95% CI: 0.6-1.1) increase in SBP. Weight and fat mass increase rapidly in PWH during the first 12 months of antiretroviral therapy and contribute to a rapid increase in SBP. Interventions to prevent excessive increase in fat mass are needed for PWH.

0154 Differences in Monocyte Activation between People with Treated HIV Infection With or Without OSA

Abstract Introduction Obstructive sleep apnea (OSA) has been associated with low grade systemic inflammation and greater cardiovascular risk, but the specific pathways mediating these effects are unclear. Monocyte activation is implicated in the development of cardiovascular disease in people with treated HIV infection. We sought to evaluate the impact of OSA on monocyte activation in people living with human immunodeficiency virus (HIV) infection. Methods Ten HIV seropositive participants with undetectable (&amp;lt;50 copies/mL) HIV viremia and at least one year of antiretroviral therapy underwent home sleep apnea testing to evaluate for the presence (apnea-hypopnea index -AHI4% ≥15 events/hour) or absence (AHI4% &amp;lt;5 events/hour) of OSA. Mononuclear cells were extracted and analyzed by flow cytometry. The composition of monocyte subsets (classical, intermediate, patrolling) was assessed using surface markers. Intracellular tumor necrosis factor alpha (TNFα), interleukin 1β (IL-1β), and interleukin 6 (IL-6) levels were measured by median fluorescence intensity (MFI, unit: au) and log-transformed. Differences in monocyte subset composition and intracellular cytokine levels between those with and without OSA were analyzed by t-test. Results Participants had a mean ± SD age of 61 ± 4.7 years, were 50% female, 80% Black race and had well-constituted CD4+ counts (mean ± SD: 934 ± 283 cells/ml). The mean AHI4% among participants with OSA (n=4) was 21.8 ± 4.4 events/hour whereas controls (n=6) had an AHI4% of 2.4 ± 2.0 events/hour (p-value = 0.001). There was no difference in the proportion of classical monocytes between groups (mean ± SD 83.8% ± 11.5% in participants with OSA vs. 84.9% ± 7.5% in controls, p=0.86). Intracellular TNFα was greater in monocytes from participants with OSA vs. controls (log-transformed MFI 3.49±0.20 au vs. 3.00±0.35 au, p=0.03). Additionally, there was a trend toward greater intracellular concentrations of IL-1β (mean log-transformed MFI 3.24±0.15 au vs. 2.95±0.48 au, p=0.22) and IL-6 (log-transformed MFI 3.28±0.16 au vs. 2.91±0.64 au, p=0.23), in participants with OSA vs. controls. Conclusion Pro-inflammatory cytokine levels are greater in monocytes obtained from people with treated HIV infection with OSA compared to those without OSA. Our findings suggest OSA may exacerbate chronic inflammation and cardiovascular risk in chronic HIV infection. Support (If Any) HL082610 and American Thoracic Society ASPIRE Fellowship

Baseline and Process Factors of Anti-Retroviral Therapy That Predict Loss to Follow-up Among People Living with HIV/AIDS in China: A Retrospective Cohort Study.

We explored the predictors and predictive models of loss to follow-up (LTFU) during the first year of anti-retroviral therapy (ART). LTFU was defined as the failure to visit the clinic for antiretroviral drugs for ≥ 90days after the last missed scheduled visit. Based on the electronic medical records of 5953 patients who were HIV positive and began ART between 2016 and 2019 in China, the LTFU rate was 7.24 (95% confidence interval 6.49-7.97) per 100 person-years during the first year of ART. ART baseline factors were associated with LTFU, but were non-optimal predictors. A model including ART process-related factors such as follow-up behaviors and physical health status had an area under the receiver operating characteristic curve of 73.4% for predicting LTFU. Therefore, the medical records of follow-up visits can be used to identify patients with a high risk of LTFU and allow interventions to be implemented proactively.

Evidence of HIV-1 Genital Shedding after One Year of Antiretroviral Therapy in Females Recently Diagnosed in Bamako, Mali.

Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by ViroseqTM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrentTM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs.

Comparative incidence of adverse drug reaction during the first and subsequent year of antiretroviral therapy in a Nigerian HIV infected Cohort.

Despite close to two decades of antiretroviral therapy (ART) in Nigeria, data on late on-onset ART-associated adverse drug reactions (ADRs) are sparse. To describe early and late-onset ADRs and compare their incidence in an outpatient HIV positive Cohort on ART. We described the incidence of clinical ADRs identified and documented in an outpatient clinic cohort of HIV-positive patients treated between June 2004 and December 2015 at a tertiary health facility in Nigeria. Incidence rates of ADRs during the first and subsequent years of ART were compared. of the 13,983 patients' data analyzed, 9317 were females (66%), and those in the age bracket of 25 to 45 years made up 78% of the studied population. During 52,411 person-years (py) of ART, 1485 incident ADRs were recorded; Incidence rate (IR) 28.3 (95% confidence interval [CI] 26.9:29.8) ADRs per 1000 person-years (py) of ART. The IR of ADRs was about two times higher in the first year of ART compared to subsequent years of treatment; crude incidence rate ratio (IRR) 1.77 (95% CI 1.59:1.97). Anemia, hypersensitivity reactions, and nervous system disorders had 7, 23, and 5 times higher incidence, respectively, in the first year of therapy, compared to subsequent years. The first year of ART is the period of highest risk of ADRs. Individual and programmatic treatment success in resource-limited settings requires strategies for early identification and management of ADR during the period of greatest risk of ADRs.

Changes in trabecular bone score and bone mineral density in Chinese HIV-Infected individuals after one year of antiretroviral therapy.

ObjectiveHuman immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with reduced bone mineral density (BMD) in persons with HIV (PWH). BMD provides information only about bone mineral quantity. Trabecular bone score (TBS) is a noninvasive tool that estimates bone microarchitecture. The aim of this study is to measure BMD and TBS of Chinese PWH after one-year ART.MethodsWe designed a retrospective study of adult Chinese PWH. Patients with a dual-energy X-ray absorptiometry (DXA) scan prior to ART initiation, and again 48 weeks later were included. Information regarding demographic and clinical history, HIV treatment history, BMD and TBS were collected. We analyzed differences in BMD and TBS over 48 weeks and associations between key risk factors and changes in BMD and TBS.ResultsOur study included 233 ​PWH (mean age ​= ​36.6 ​± ​11.1 years). Before ART initiation, 19.3% of PWH had normal BMD but abnormal TBS. Both BMD and TBS decreased after one-year ART. TDF and LPV/r-containing regimens were associated with greater declines in BMD at different site. Traditional risk factors such as old age, low BMI and female sex were associated with lower baseline TBS. Greater change in TBS over one year was associated with lower BMI and lower baseline CD4+ cell count, but unlike BMD measures, it was not correlated with treatment with TDF and LPV/r in our study population.ConclusionsWe present the first longitudinal analysis of change in TBS over 48 weeks compared with BMD among Asian PWH receiving ART. Before ART initiation, approximately 20% of PWH with impaired bone microarchitecture would not have been identified if DXA were used alone to assess for bone damage. Both BMD and TBS decreased after one-year ART. Change in TBS was not associated with different antiretroviral agents.The translational potential of this articleThe trabecular microarchitecture measured indirectly by TBS may provide clinicians additional information about bone damage in PWH.

Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations?

Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations?

PIN39 Thirty Two YEARS of Antiretroviral Therapy (ART) for People Living with HIV in Spain: HAS IT Been an Efficient Intervention?

The aim of this study is to estimate the clinical and economic impact of ART in Spain over a 32-year period (1987-2018). A cost-benefit analysis was performed, using a second-order Monte Carlo simulation model, from a societal (base case) and National Health Service (NHS) perspective. New cases of HIV, AIDS and associated deaths in Spain were obtained from SINIVIH registry and UNAIDS. Local projections of new HIV cases, AIDS cases, and AIDS related deaths in a scenario without ART were estimated by triple exponential smoothing. HIV and AIDS cases averted and deaths prevented, were estimated. ART expenditure and the benefits of avoiding HIV infections and AIDS cases were obtained from National HIV plan assessment reports and Market Research data. The monetary value of a life was estimated as the local annual GDP per capita. The model’s assumptions and data were validated by a panel of 4 Spanish experts. The NHS invested 6,185 million euros on ART over 32 years. In that period, 323,651 AIDS deaths, 500,129 AIDS cases and 161,417 HIV cases were averted, with total savings of 41,997 million euros. The net benefit (net savings) associated with these results is estimated at 35,812 million euros (social perspective) and 1,032 million euros (NHS perspective). ART is a profitable investment as it would render benefit/cost ratios of 6.79 (95%CI 5.39-8.35) and 1.17 (95% CI: 1.16; 1.18) from a social and NHS perspective, respectively. Subanalysis of ART drugs marketed by Gilead Sciences (2002-2018), brought out a net benefit of 8,361 million euros, 23% of the total (benefit/cost ratio of 3.2 from a social perspective). The use of ART over 32 years in Spain has highly limited the amount of deaths from AIDS as well as new cases of both HIV and AIDS, while simultaneouly providing significant economic savings.

Immunovirological treatment outcomes after 2 years of antiretroviral therapy in children living with the human immune deficiency virus in Lagos Nigeria

Background/objective: The World Health Organization (WHO) recommends routine assessment of antiretroviral treatment outcomes to detect treatment failure early and prevent the development of drug resistance. The aim of this study was to describe treatment outcomes of antiretroviral therapy (ART) over 2 years in children living with the human immune deficiency virus enrolled in the paediatric HIV clinic at the Lagos UniversityTeaching Hospital (LUTH).Materials and methods: This was a retrospective study of antiretroviral treatment outcomes in 278 children receiving antiretroviral therapy at the paediatric HIV clinic of LUTH. Demographic, clinical and laboratory data were retrospectively collected from clinical records of pediatric patientswho received antiretroviral therapy for 2 years ( from November 2015 to December 2017) . Virological failure was defined as viral load &gt; 400 copies/ml and immunological failure was defined as a CD4 count &lt;100 cells/mm3 or CD4 % &lt;15% after receiving antiretroviral agents for 12 months. Data was analysed using graph pad prism version 5.0.Results: After 12 months on antiretroviral therapy (ART), 101 (36%) had virological failure while 14 (5%) and 36 (13%) failed immunologically [CD4 count &lt;100 cells/mn3 and CD4 &lt;15% respectively]. Virological blips were observed at 24 months in 6.1% of patients while immunovirological discordance occurred in 30% of patients (poor virological clearance despite good immunological recovery) . High baseline viral load (&gt;5000 copies/ml), poor adherence (&lt;95%) and low baseline CD4 counts (101-249 cells/mn3) were significantly associated with virological failure, while low baseline CD4 counts (&lt;350 cells/mn3) and poor adherence (&lt;95%) were significantly associated with immunologic failure.Conclusion: The treatment outcomes observed in this study are similar to those reported in earlier studies. At 1 and 2 years of antiretroviral therapy , there was immune restoration however 101 (36%) and 87 (31%) respectively had virological failure despite good adherence to therapy and good Immunological restoration. This calls for early initiation and switch to second and third line drugs .&#x0D; Key words: Human immunodeficiency virus (HIV), zidovudine, lamivudine, nevirapine, virological blips, immunovirological discordance , children, Nigeria.

Blood pressure, T cells, and mortality in people with HIV in Tanzania during the first 2years of antiretroviral therapy.

Cardiovascular disease is now a leading cause of mortality in people with HIV (PWH). High blood pressure is the major driver of cardiovascular disease. Despite this, little is known about blood pressure in PWH during the early years of antiretroviral therapy (ART). In this prospective cohort study in Tanzania, the authors conducted unobserved blood pressure measurements at enrollment, 3, 6, 12, 18, and 24months in 500 PWH initiating ART and 504 HIV-uninfected adults. The authors excluded measurements taken on antihypertensive medications. Although PWH had a significantly lower blood pressure before ART initiation, they had a significantly greater increase in blood pressure during the first 2years of ART compared to HIV-uninfected controls. Blood pressure correlates in PWH differed from HIV-uninfected controls. In PWH, lower baseline CD4+ T-cell counts were associated with lower blood pressure, and greater increases in CD4+ T-cell counts on ART were associated with greater increases in blood pressure, both on average and within individuals. In addition, PWH with a systolic blood pressure (SBP) <90mmHg at the time of ART initiation had ~30% mortality in the following 3months due to occult infections. These patients require careful investigation for occult infections, and those with tuberculosis may benefit from corticosteroids.

Determine TB-LAM point-of-care tuberculosis assay predicts poor outcomes in outpatients during their first year of antiretroviral therapy in South Africa

BackgroundDetermine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART.MethodsConsecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at three months and one year of follow-up.Results468 patients with a median CD4 count of 59 cells/uL were enrolled. There were 140 patients (29.9%) with newly diagnosed TB in the first year of follow-up of which 79 (56.4%) were microbiologically-confirmed. A total of 18% (n = 84) required hospital admission and 12.2% (n = 57) died within a year of study entry. 38 out of 468 (8.1%) patients retrospectively tested urine-LAM positive – including 19.0% of those with microbiologically-proven TB diagnoses (n = 15/79) and 23.0% (n = 14/61) of those with clinical-only TB diagnoses; 9 of 38 (23.7%) of patients retrospectively testing LAM positive were never diagnosed with TB under routine program conditions. Among all patients (n = 468) in the first year of follow-up, a positive urine-LAM result was strongly associated with all-cause hospitalization and mortality with a corresponding adjusted hazard ratio (aHR) of 3.7 (95%CI, 1.9–7.1) and 2.6 (95%, 1.2–5.7), respectively.ConclusionsSystematic urine-LAM testing among ART-naïve HIV-positive outpatients with CD4 counts < 100 cells/uL detected TB cases that were missed under routine programme conditions and was highly predictive for subsequent hospitalization and mortality in the first year of ART.