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Quantitative ultrasonometry: An alternative and easy method to evaluate bone quality in people living with human immunodeficiency virus.
Segal, E, Hassoun, G, Maor, C, Shahar, E
Journal of musculoskeletal & neuronal interactions. 2019;(1):112-117
Abstract
BACKGROUND HIV infection and antiretroviral therapy (ART) are associated with bone mineral loss. DXA is the gold standard method to evaluate the status of bone mineral density (BMD). However, it is not always readily available. An easy method is needed to evaluate bone quality in those infected with HIV. OBJECTIVE To evaluate portable quantitative ultrasonometry (QUS) as an alternative technique to provide information about bone density, bone strength, and the bone turnover markers in HIV-infected people. METHODS A total of 69 men took part (34 HIV-infected men were matched with 35 non-HIV-infected men) in the study. Bone mineral status was assessed by the Achilles quantitative ultrasonometer at the calcaneal heel. The HIV status was recorded for all HIV-infected patients. Calcium-regulating hormones and bone turnover markers were assessed in all participants. RESULTS The mean age was 47.8±7.8 years and 49.1±6.00 years for the HIV-infected and non-infected population, respectively. The bone quality expressed as Stiffness index (SI) was reduced in HIV-infected patients. Bone turnover markers were higher in the HIV-infected patients, P1NP (ng/mL) was 48.0±14.3 vs 41.1±15.2 (P=0.057), and the (CTx)) (ng/mL) was 0.41±0.18 vs 0.29±0.11 (P=0.002). CONCLUSIONS QUS is easy to use. Hence, QUS could be used as alternative method for screening of HIV patients for altered bone status.
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Burden of anemia and its association with HAART in HIV infected children in Ethiopia: a systematic review and meta-analysis.
Wagnew, F, Eshetie, S, Alebel, A, Tesema, C, Kibret, GD, Gebrie, A, Dessie, G, Abajobir, AA
BMC infectious diseases. 2019;(1):1032
Abstract
BACKGROUND Anemia is a common problem in HIV (human immunodeficiency virus) infected patients, and is associated with decreased functional capacity and quality of life. Ethiopia is one of the countries which has expanded highly active antiretroviral treatment (HAART) over the past years. The effect of HAART on anemia among HIV remains inconsistent and inconclusive, particularly in children. This study thus aimed to synthesize the prevalence of anemia among HIV infected Ethiopian children and its association with HAART initiation. METHODS MEDLINE/PubMed, EMBASE, PsycINFO, Web of Science and Google scholar were used to identify 12 eligible studies reporting an association between anemia and HIV using a priori set criteria. PRISMA guideline was used to systematically review and meta-analysis these studies. Details of sample size, magnitude of effect sizes, including odds ratio (OR) and standard errors were extracted. Random-effects model was used to calculate the pooled estimates using STATA/SE version-14. I2 and meta-bias statistics assessed heterogeneity and publication bias of the included studies. Sub-group analyses, based on study designs, were also carried out. RESULTS In Ethiopia, the overall prevalence of anemia in HIV infected children was 22.3% (95% CI: 18.5-26.0%). The OR of anemia-HIV/AIDS comorbidity was 0.4 (95% CI, 0.2-0.5) in HAART initiated children as compared to non-initiated counterparts. Meta-bias and funnel plot detected no publication bias. CONCLUSION On aggregate, anemia is a common comorbidity in pediatric HIV patients. HAART was significantly associated with a reduced anemia-HIV/AIDS comorbidity. Prompt start of HAART might help decreasing the prevalence of anemia and its subsequent complications.
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Acute Promyelocytic Leukemia and HIV: Case Reports and a Review of the Literature.
Kunitomi, A, Hasegawa, Y, Lmamura, J, Yokomaku, Y, Tokunaga, T, Miyata, Y, Iida, H, Nagai, H
Internal medicine (Tokyo, Japan). 2019;(16):2387-2391
Abstract
Acute promyelocytic leukemia (APL) in human immunodeficiency virus (HIV)-infected individuals is very rare. There is currently no consensus regarding the use of anti-cancer drugs with highly active anti-retroviral therapy (ART) in these patients due to their small number. We herein report two cases of APL with HIV-infected patients. Both cases received all-trans-retinoic acid-containing chemotherapies and achieved complete remission. ART was continued throughout the treatment course. The clinical course of these cases suggests that it is preferable to perform standard chemotherapy for APL with ART if patients have an adequate performance status.
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A 24-week pilot study of dual maintenance therapy with raltegravir and lamivudine.
de Lazzari, E, Lonca, M, Rojas, J, Gonzalez-Cordon, A, Blanch, J, Inciarte, A, Tricas, A, Rodriguez, A, Martinez-Rebollar, M, Laguno, M, et al
AIDS (London, England). 2019;(12):1891-1896
Abstract
BACKGROUND There is an increasing interest in two-drug regimens. We hypothesized that maintenance therapy with raltegravir and lamivudine would keep HIV-1 suppressed and be well tolerated. METHODS Virally suppressed HIV-1-infected adults without previous viral failures or known resistance mutations to integrase inhibitors or 3TC/FTC or chronic hepatitis B were randomized 2 : 1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. Primary outcome was the proportion of patients free of therapeutic failure (defined as viral failure, change in treatment for any reason, consent withdrawal, loss to follow-up or death) at week 24. Secondary outcomes were changes in laboratory, body composition, sleep quality, adherence, and adverse effects. RESULTS There were 75 patients included: men 78%; median age 50 years; median CD4 622/μl. At week 24, 7 (9%) patients had therapeutic failure: raltegravir and lamivudine 2 (4%) vs. control 5 (20%). The difference in proportions of therapeutic failures raltegravir and lamivudine minus control was -0.159 (95% confidence interval: -0.353 to -0.012). There was a trend to more weight gain with raltegravir and lamivudine, but no significant changes in other secondary outcomes. Sixty-four percent of patients in each arm had at least one adverse effect. Two (6%) patients in control arm and 4 (7%) patients in raltegravir and lamivudine arm had severe adverse effects. CONCLUSION This pilot study suggests that switching to raltegravir along with lamivudine in patients with viral suppression maintains efficacy and is well tolerated. A larger study of longer duration is required to confirm these findings.
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Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial.
Orkin, C, Squires, KE, Molina, JM, Sax, PE, Wong, WW, Sussmann, O, Kaplan, R, Lupinacci, L, Rodgers, A, Xu, X, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019;(4):535-544
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Abstract
BACKGROUND Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. METHODS DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment-naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). RESULTS Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (-1.6 vs +8.7 mg/dL and -3.8 vs +13.3 mg/dL, respectively). CONCLUSIONS In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non-HDL-C compared with EFV/FTC/TDF. CLINICAL TRIALS REGISTRATION NCT02403674.
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Progressive disseminated histoplasmosis in Latin America and the Caribbean in people receiving highly active antiretroviral therapy for HIV infection: A systematic review.
Cano-Torres, JO, Olmedo-Reneaum, A, Esquivel-Sánchez, JM, Camiro-Zuñiga, A, Pérez-Carrisoza, A, Madrigal-Iberri, C, Flores-Miranda, R, Ramírez-González, LE, Belaunzarán-Zamudio, PF
Medical mycology. 2019;(7):791-799
Abstract
Histoplasmosis is the most clinically significant mycosis in Latin America; still it has been neglected in people with human immunodeficiency virus (HIV). There is limited information about its contribution to morbidity and mortality in this population. We conducted a systematic review of scientific literature to provide an estimation of the frequency and mortality of histoplasmosis among people with HIV receiving highly active antiretroviral therapy (HAART) in Latin America, and factors associated with mortality. We searched articles in PubMed, Scopus, WHO Global health library, and Scielo using different combination of terms including "histoplasmosis" and HAART. We identified 949 articles, removed 662 duplicated; screened 287 abstracts; reviewed full text of 53 articles; and selected 15 articles that provided information on the number of patients studied, included patients receiving ART, and reported any measure of frequency estimate for qualitative synthesis. Studies were conducted in Argentina (n = 4), Brazil (n = 6), Colombia (n = 2), French Guyana and the Bahamas (=2), and Guatemala (n = 1). Heterogeneity of studies characteristics precluded any aggregated estimates. Histoplamosis was frequent in these cohort studies and mortality was high despite the use of HAART. Low CD4 counts, delayed HAART initiation and poor adherence were related to increased incidence, poor prognosis and increased mortality, respectively. Histoplasmosis may be an important contributor to mortality in people with HIV in Latin America. Diagnostic delays represent an important limitation for improving care of patients suspected to have histoplasmosis. Reducing histoplasmosis diagnostic delays and therapy initiation is needed to further decrease mortality.
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Hepatitis B virus coinfection is associated with high early mortality in HIV-infected Tanzanians on antiretroviral therapy.
Christian, B, Fabian, E, Macha, I, Mpangala, S, Thio, CL, Ulenga, N, Mugusi, F, Ammerman, LR, Fawzi, W, Green, R, et al
AIDS (London, England). 2019;(3):465-473
Abstract
OBJECTIVES There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. DESIGN Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. METHODS Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. RESULTS A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. CONCLUSION High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.
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Immediate Versus Deferred Switching From a Boosted Protease Inhibitor-based Regimen to a Dolutegravir-based Regimen in Virologically Suppressed Patients With High Cardiovascular Risk or Age ≥50 Years: Final 96-Week Results of the NEAT022 Study.
Gatell, JM, Assoumou, L, Moyle, G, Waters, L, Johnson, M, Domingo, P, Fox, J, Martinez, E, Stellbrink, HJ, Guaraldi, G, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019;(4):597-606
Abstract
BACKGROUND Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)-based regimen to a dolutegravir (DTG)-based regimen may improve lipid profile. METHODS European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)-infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs). RESULTS Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, -.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P < .001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. CONCLUSIONS Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile. CLINICAL TRIALS REGISTRATION NCT02098837 and EudraCT: 2013-003704-39.
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Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial.
Molina, JM, Squires, K, Sax, PE, Cahn, P, Lombaard, J, DeJesus, E, Lai, MT, Xu, X, Rodgers, A, Lupinacci, L, et al
The lancet. HIV. 2018;(5):e211-e220
Abstract
BACKGROUND Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We compared doravirine with ritonavir-boosted darunavir, when both were given with two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with previously untreated HIV-1 infection. METHODS In this randomised, controlled, double-blind, multicentre, non-inferiority trial, adults with HIV-1 infection were screened and enrolled at 125 clinical centres in 15 countries. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy with plasma HIV-1 RNA of at least 1000 copies per mL at screening. Participants who had previously been treated for a viral infection other than HIV-1, those taking immunosuppressive drugs, and individuals with active acute hepatitis were excluded. Participants were randomly assigned (1:1) via an interactive voice and web response system to receive oral doravirine 100 mg or darunavir 800 mg plus ritonavir 100 mg once daily, with two investigator-selected NRTIs (tenofovir and emtricitabine or abacavir and lamivudine) for up to 96 weeks. Randomisation was stratified by HIV-1 RNA measurements at screening (≤100 000 vs >100 000 copies per mL) and the NRTI pair. Study participants, funding institution staff, investigators, and study site personnel were masked to treatment group assignment. The primary efficacy endpoint was the proportion of participants achieving HIV-1 RNA of less than 50 copies per mL at week 48 defined by the US Food and Drug Administration snapshot algorithm, with non-inferiority established if the lower bound of the two-sided 95% CI for the treatment difference (doravirine minus darunavir) was greater than -10 percentage points. All participants who received at least one dose of study drug were included in the primary efficacy and safety analyses. This trial is active, but not recruiting, and is registered with ClinicalTrials.gov, number NCT02275780. FINDINGS Between Dec 1, 2014, and Oct 20, 2015, 1027 participants were screened for eligibility, of whom 769 participants were randomly assigned to treatment (385 with doravirine and 384 with ritonavir-boosted darunavir). 56 participants discontinued treatment in the doravirine group compared with 71 in the darunavir group, mostly due to loss to follow-up. 383 participants who received doravirine and 383 who received darunavir were included in the primary efficacy analyses. At week 48, 321 (84%) participants in the doravirine group and 306 (80%) in the darunavir group achieved plasma HIV-1 RNA of less than 50 copies per mL (difference 3·9%, 95% CI -1·6 to 9·4), indicating non-inferiority of the doravirine regimen. The most common study drug-related adverse events were diarrhoea (21 [5%] of 383 participants in the doravirine group and 49 [13%] of 383 participants in the darunavir group), nausea (25 [7%] vs 29 [8%]), and headache (23 [6%] vs ten [3%]). 18 participants (six [2%] of 383 participants in the doravirine group vs 12 [3%] of 383 participants in the darunavir group) discontinued treatment due to adverse events, which were considered drug-related in four (1%) participants in the doravirine group and 8 (2%) participants in the darunavir group. Serious adverse events occurred in 19 (5%) of 383 participants in the doravirine group and 23 (6%) of 383 in the darunavir roup, and were considered study-drug related in one (<1%) participant of each group. INTERPRETATION In treatment-naive adults with HIV-1 infection, doravirine combined with two NRTIs might offer a valuable treatment option for adults with previously untreated HIV-1 infection. FUNDING Merck & Co.
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Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study.
Ocampo, A, Domingo, P, Fernández, P, Diz, J, Barberá, JR, Sepúlveda, MA, Salgado, X, Rodriguez, M, Santos, J, Yzusqui, M, et al
The Journal of antimicrobial chemotherapy. 2018;(8):2171-2176
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Abstract
OBJECTIVES To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. METHODS PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. RESULTS A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ± 38.4 mg/dL; week 48: 171.0 ± 35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ± 1.2; week 48: 4.0 ± 1.2), HDL (baseline: 49.1 ± 12.0 mg/dL; week 48: 49.2 ± 45.8 mg/dL), LDL (baseline: 119.2 ± 30.2 mg/dL; week 48: 114.2 ± 110.7 mg/dL), and triglycerides (baseline: 136.6 ± 86.8 mg/dL; week 48: 113.4 ± 67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ± 48.8 mg/dL; week 48: 173.4 ± 36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ± 1.6; week 48: 4.0 ± 1.2), HDL (baseline: 46.4 ± 12.5 mg/dL; week 48: 52.1 ± 54.4 mg/dL), LDL (baseline: 127.0 ± 36.3 mg/dL; week 48: 111.4 ± 35.8 mg/dL), and triglycerides (baseline: 167.6 ± 107.7 mg/dL; week 48: 122.7 ± 72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. CONCLUSIONS RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.