Diagnosis and Management of HIV Infection

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Diagnostic Microbiology and Infectious Disease".

Deadline for manuscript submissions: closed (20 January 2022) | Viewed by 28036

Special Issue Editor

Infectious and Tropical Diseases Unit, Siena University Hospital, 53100 Siena, Italy
Interests: diagnosis and treatment of HIV infection; viral hepatitis and other viral diseases; infections in immunocompromised patients

Special Issue Information

Dear Colleagues,

Despite the availability of effective combination antiretroviral therapy (ART), HIV infection is still a major global health threat. The UNAIDS 90–90–90 target (which means diagnosing 90% of all people living with HIV (PLWH), providing ART to 90% of those diagnosed, and achieving viral suppression for 90% of those on ART), advocated to end the AIDS epidemic, is unlikely to be met soon in many areas. Crucial factors that need to be addressed to reach this goal are scaling up HIV testing, improving access to ART, optimizing ART based on resistance monitoring, reducing loss to follow-up for those on ART, and optimally diagnosing and managing comorbidities that could impact ART adherence and final prognosis.  Moreover, patients achieving viral suppression and adequate immune reconstitution on ART represent a challenging population. Accelerated aging and an increased prevalence of non-AIDS-related comorbidities (e.g., cancers, neurocognitive, cardiovascular, hepatic, renal and bone diseases) make PLWH a difficult-to-treat population. Both HIV-specific expertise and internal medicine/primary care knowledge are required to optimally manage PLWH. On this basis, further research is needed to better understand the complex aspects of HIV infection and to optimize strategies for its diagnosis and management.

The aim of this Special Issue is to publish high-quality research on any aspect of diagnosis and management of HIV infection and its related comorbidities. Original research articles and reviews summarizing the state of ART of HIV medicine are welcome.

Dr. Massimiliano Fabbiani
Guest Editor

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Keywords

  • HIV-1
  • HIV-2
  • HIV testing
  • HIV-RNA
  • HIV-DNA
  • HIV viral load
  • genotypic resistance test
  • phenotypic resistance test
  • antiretroviral therapy
  • opportunistic infections
  • non-AIDS-related comorbidities

Published Papers (10 papers)

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Research

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10 pages, 483 KiB  
Article
Switching to a Bictegravir Single Tablet Regimen in Elderly People Living with HIV-1: Data Analysis from the BICTEL Cohort
by Alessandro Lazzaro, Elio Gentilini Cacciola, Cristian Borrazzo, Giuseppe Pietro Innocenti, Eugenio Nelson Cavallari, Ivano Mezzaroma, Mario Falciano, Caterina Fimiani, Claudio Maria Mastroianni, Giancarlo Ceccarelli and Gabriella d’Ettorre
Diagnostics 2022, 12(1), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12010076 - 29 Dec 2021
Cited by 9 | Viewed by 1973
Abstract
Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, [...] Read more.
Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, we recruited an observational retrospective real-life cohort including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the provenience treatment regimen. After 48 weeks of follow-up, 147 PLWH were included and 93 were older than 55 years. PLWH with HIV-RNA < 37 copies/mL increased from 140 to 146 (p < 0.033). Among the overall population, we observed an increase in CD4+ T cells count by 30.1% (p-value < 0.001), in CD8+ T cells count by 7.1% (p-value = 0.004) and in CD4+/CD8+ ratio by 21.5% (p-value < 0.001). Lipidic profile was characterized by decreasing total cholesterol/HDL ratio by 8% (p-value < 0.001) and LDL by 6.8% (p-value = 0.007). Total body weight increased by 1.8% (p-value = 0.014) and BMI by 4.2% (p-value < 0.001), even remaining within the healthy range. Hepatic and renal profile were not altered by the switch, nor were adverse events and/or discontinuations events detected. In conclusion, BIC/FTC/TAF is effective, safe and well tolerated in real life and among PLWH older than 55. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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11 pages, 659 KiB  
Article
Clinical Profile of 24 AIDS Patients with Cryptococcal Meningitis in the HAART Era: A Report from an Infectious Diseases Tertiary Hospital in Western Romania
by Iosif Marincu, Cosmin Citu, Iulia Vidican, Felix Bratosin, Mihai Mares, Oana Suciu, Stefan Frent, Adrian Vasile Bota, Madalina Timircan, Melania Lavinia Bratu and Mirela Loredana Grigoras
Diagnostics 2022, 12(1), 54; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12010054 - 28 Dec 2021
Cited by 2 | Viewed by 2528
Abstract
Management of cryptococcal infections among patients suffering from acquired immunodeficiency syndrome (AIDS) represents a medical challenge. This retrospective study aims to describe the disease management and outcomes among 24 AIDS patients who suffered from Cryptococcus neoformans meningitis. The parameters evaluated from our patients’ [...] Read more.
Management of cryptococcal infections among patients suffering from acquired immunodeficiency syndrome (AIDS) represents a medical challenge. This retrospective study aims to describe the disease management and outcomes among 24 AIDS patients who suffered from Cryptococcus neoformans meningitis. The parameters evaluated from our patients’ database records include epidemiological data, clinical manifestations, biochemical and microbiological analysis of patients’ cerebrospinal fluid (CSF), treatment profiles, and disease outcomes. All patients included in the study had a lymphocyte count of less than 200 CD4/mm3. Of the 24 patients included in this study, five had been diagnosed with HIV infection since childhood, after receiving HIV-infected blood transfusions. The most prominent symptom was fatigue in 62.5% of patients, followed by nausea/vomiting and headache. Seven patients had liver cirrhosis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, while Kaposi sarcoma and cerebral toxoplasmosis were found in two patients. Six out of 24 patients died due to bacterial sepsis and acute respiratory distress syndrome (ARDS). High intracranial pressure was the strongest predictive factor for mortality (OR = 2.9), followed by ARDS (OR = 1.8), seizures at disease onset (OR = 1.4), and diabetes mellitus (OR = 1.2). Interestingly, patients younger than 40 years old had a significantly lower survival rate than that of the older patients. Before developing Cryptococcal meningitis, all patients had low adherence to the early ART treatment scheme and skipped the follow-up visits. All patients received a combination of amphotericin B and flucytosine as induction therapy, adding fluconazole for maintenance. Simultaneously, AIDS HAART was initiated at diagnosis of the cryptococcal infection. A combined regimen of antifungals and highly active antiretroviral therapy showed improved patient recovery with minor side effects. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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14 pages, 1069 KiB  
Article
Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection
by Barbara Rossetti, Valentina Borgo, Arianna Emiliozzi, Marta Colaneri, Giacomo Zanelli, Miriana d’Alessandro, Davide Motta, Laura Maiocchi, Francesca Montagnani, Maria Cristina Moioli, Chiara Baiguera, Margherita Sambo, Teresa Chiara Pieri, Pietro Valsecchi, Raffaele Bruno, Massimo Puoti and Massimiliano Fabbiani
Diagnostics 2022, 12(1), 14; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12010014 - 22 Dec 2021
Cited by 3 | Viewed by 2932
Abstract
Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals [...] Read more.
Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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14 pages, 1325 KiB  
Article
Immunological and Clinical Impact of DAA-Mediated HCV Eradication in a Cohort of HIV/HCV Coinfected Patients: Monocentric Italian Experience
by Andrea Marino, Gabriella Zafarana, Manuela Ceccarelli, Federica Cosentino, Vittoria Moscatt, Gabriele Bruno, Roberto Bruno, Francesco Benanti, Bruno Cacopardo and Benedetto Maurizio Celesia
Diagnostics 2021, 11(12), 2336; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11122336 - 11 Dec 2021
Cited by 15 | Viewed by 2280
Abstract
HCV treatment became available for all infected patients regardless of their comorbidities, especially for HIV coinfected subjects, leading to an improvement in both clinical and immunological conditions. We retrospectively analyzed a cohort of HIV/HCV coinfected patients treated with DAA therapies; data regarding epidemiological, [...] Read more.
HCV treatment became available for all infected patients regardless of their comorbidities, especially for HIV coinfected subjects, leading to an improvement in both clinical and immunological conditions. We retrospectively analyzed a cohort of HIV/HCV coinfected patients treated with DAA therapies; data regarding epidemiological, viral-immunological, and hepatic parameters before and after DAA administration have been collected. Drug-drug interactions between DAA and both antiretroviral therapy and non-ART-drugs were also evaluated; the study showed the efficacy of DAA schedules in HCV eradication also for HIV/HCV patients with multiple comorbidities and assuming many different drugs. Principal issues are still represented by drug interactions, pill burden, and patients’ compliance. These concerns have to be taken into account, especially in HIV patients for whom the immunological state and ART interactions should always be considered. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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10 pages, 456 KiB  
Article
Seroprevalence of SARS-CoV-2 Antibodies in HIV-Infected Patients in Rome, Italy during the COVID-19 Outbreak
by Francesca Lombardi, Rosalba Ricci, Simone Belmonti, Massimiliano Fabbiani, Alberto Borghetti, Gianmaria Baldin, Arturo Ciccullo, Enrica Tamburrini, Elena Visconti, Maurizio Sanguinetti and Simona Di Giambenedetto
Diagnostics 2021, 11(7), 1154; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11071154 - 24 Jun 2021
Cited by 8 | Viewed by 1844
Abstract
Background: this study aimed to determine the proportion of people living with HIV (PLWH) with anti-SARS-CoV-2 IgG antibodies in a large sample from a single HIV referral center in Rome, Italy; the time-frame included both the first and the second wave of the [...] Read more.
Background: this study aimed to determine the proportion of people living with HIV (PLWH) with anti-SARS-CoV-2 IgG antibodies in a large sample from a single HIV referral center in Rome, Italy; the time-frame included both the first and the second wave of the Italian COVID-19 pandemic; Methods: we conducted a cross-sectional study on stored cryopreserved samples from 1 March 2020 to 30 November 2020. Total antibodies against SARS-CoV-2 were preliminarily tested using a chemiluminescent immunoassay. Positive results were re-tested with an ELISA assay as an IgG confirmatory test; Results: overall, 1389 samples were analyzed from 1106 PLWH: 69% males, median age 53 years, 94% on antiretroviral treatment, 93% with HIV-RNA < 50 copies/mL, median CD4 cell count 610 cell/µL. Our analysis revealed a total of n = 8 patients who tested IgG positive during the study period. Seroprevalence was equal to 0% in the first months (March–June); this started to increase in July and reached a maximum rate of 1.59% in October 2020. The overall seroprevalence was 0.72% (8/1106, 95% CI 0.37–1.42). Conclusion: our findings from this setting show a low IgG SARS-CoV-2 prevalence among PLWH as compared to data available from the general population. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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11 pages, 850 KiB  
Article
Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
by Giulia Caligaris, Mattia Trunfio, Valeria Ghisetti, Jessica Cusato, Marco Nigra, Cristiana Atzori, Daniele Imperiale, Stefano Bonora, Giovanni Di Perri and Andrea Calcagno
Diagnostics 2021, 11(5), 867; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11050867 - 12 May 2021
Cited by 10 | Viewed by 2253
Abstract
Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral [...] Read more.
Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naïve and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38–52) years in naïve and 49 (43–57) years in treated subjects. BBBi was observed in 35.4% naïve and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naïve participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naïve and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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Review

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18 pages, 2256 KiB  
Review
Quantification of Total HIV DNA as a Marker to Measure Viral Reservoir: Methods and Potential Implications for Clinical Practice
by Simone Belmonti, Simona Di Giambenedetto and Francesca Lombardi
Diagnostics 2022, 12(1), 39; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12010039 - 24 Dec 2021
Cited by 6 | Viewed by 2950
Abstract
The focus of this review is to examine the importance of quantifying total HIV DNA to target the HIV reservoir and the clinical implications and challenges involved in its future application in clinical practice. Despite intrinsic limitations, the quantification of total HIV DNA [...] Read more.
The focus of this review is to examine the importance of quantifying total HIV DNA to target the HIV reservoir and the clinical implications and challenges involved in its future application in clinical practice. Despite intrinsic limitations, the quantification of total HIV DNA is currently the most widely used marker for exploring the HIV reservoir. As it allows estimating all forms of HIV DNA in the infected cells, total HIV DNA load is the biomarker of the HIV reservoir that provides most of the insights into HIV pathogenesis. The clinical role of total HIV-DNA in both untreated and treated patients is extensively supported by important lines of evidence. Thus, predictive models that include total HIV DNA load together with other variables could constitute a prognostic tool for use in clinical practice. To date, however, this marker has been primarily used in experimental evaluations. The main challenge is technical. Although the implementation of droplet digital PCR could improve analytical performance over real-time PCR, the lack of standardization has made cross-comparisons of the data difficult. An effort by investigators to compare protocols is needed. Furthermore, the main effort now should be to involve the biomedical industry in the development of certified assays for in vitro diagnostics use. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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22 pages, 407 KiB  
Review
A Step Closer to the “Fourth 90”: A Practical Narrative Review of Diagnosis and Management of Nutritional Issues of People Living with HIV
by Davide Fiore Bavaro, Paola Laghetti, Mariacristina Poliseno, Nicolò De Gennaro, Francesco Di Gennaro and Annalisa Saracino
Diagnostics 2021, 11(11), 2047; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11112047 - 04 Nov 2021
Cited by 4 | Viewed by 1894
Abstract
The quality of life of people living with HIV (PLWH) has remarkably increased thanks to the introduction of combined antiretroviral therapy. Still, PLWH are exposed to an increased risk of cardiovascular diseases, diabetes, chronic kidney disease, and liver disease. Hence, the purpose of [...] Read more.
The quality of life of people living with HIV (PLWH) has remarkably increased thanks to the introduction of combined antiretroviral therapy. Still, PLWH are exposed to an increased risk of cardiovascular diseases, diabetes, chronic kidney disease, and liver disease. Hence, the purpose of this review is to summarize the current knowledge about diagnosis and nutritional management with specific indication of macro and micronutrients intake for the main comorbidities of PLWH. In fact, a prompt diagnosis and management of lifestyle behaviors are fundamental steps to reach the “fourth 90”. To achieve an early diagnosis of these comorbidities, clinicians have at their disposal algorithms such as the Framingham Score to assess cardiovascular risk; transient elastography and liver biopsy to detect NAFLD and NASH; and markers such as the oral glucose tolerance test and GFR to identify glucose impairment and renal failure, respectively. Furthermore, maintenance of ideal body weight is the goal for reducing cardiovascular risk and to improve diabetes, steatosis and fibrosis; while Mediterranean and low-carbohydrate diets are the dietetic approaches proposed for cardioprotective effects and for glycemic control, respectively. Conversely, diet management of chronic kidney disease requires different nutritional assessment, especially regarding protein intake, according to disease stage and eventually concomitant diabetes. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
24 pages, 3313 KiB  
Review
International HIV Dementia Scale for HIV-Associated Neurocognitive Disorders: A Systematic Review and Meta-Analysis
by Elena Cecilia Rosca, Philippe Tadger, Amalia Cornea, Raluca Tudor, Cristian Oancea and Mihaela Simu
Diagnostics 2021, 11(6), 1124; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11061124 - 20 Jun 2021
Cited by 13 | Viewed by 3628
Abstract
The present study aims to systematically review the evidence on the accuracy of the International HIV Dementia Scale (IHDS) test for diagnosing human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) and outline the quality and quantity of research evidence available on the accuracy of [...] Read more.
The present study aims to systematically review the evidence on the accuracy of the International HIV Dementia Scale (IHDS) test for diagnosing human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) and outline the quality and quantity of research evidence available on the accuracy of IHDS in people living with HIV. We conducted a systematic literature review, searching five databases from inception until July 2020. We extracted dichotomized positive and negative test results at various thresholds and calculated the sensitivity and specificity of IHDS. Quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria. Fifteen cross-sectional studies, published between 2011 and 2018, met the inclusion criteria for meta-analysis. Overall, 3760 patients were included, but most studies recruited small samples. We assessed most studies as being applicable to the review question, though we had concerns about the selection of participants in three studies. The accuracy of IHDS was investigated at thirteen cut-off points (scores 6–12). The threshold of 10 is the most useful for optimal HAND screening (including asymptomatic neurocognitive disorder, symptomatic HAND, and HIV-associated dementia) with fair diagnostic accuracy. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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22 pages, 1409 KiB  
Review
Dolutegravir Plus Lamivudine Two-Drug Regimen: Safety, Efficacy and Diagnostic Considerations for Its Use in Real-Life Clinical Practice—A Refined Approach in the COVID-19 Era
by Valeria Cento and Carlo Federico Perno
Diagnostics 2021, 11(5), 809; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11050809 - 29 Apr 2021
Cited by 7 | Viewed by 3470
Abstract
The diagnostic and therapeutic management of the Coronavirus Disease 2019 (COVID-19) pandemic in the HIV population brought some known criticalities (and opportunities) to the forefront, for both those who are facing their first therapeutic line today, and for those already well viro-suppressed. The [...] Read more.
The diagnostic and therapeutic management of the Coronavirus Disease 2019 (COVID-19) pandemic in the HIV population brought some known criticalities (and opportunities) to the forefront, for both those who are facing their first therapeutic line today, and for those already well viro-suppressed. The clinical, socioeconomic, and psychological impact of the COVID-19 pandemic should not affect the long-term care of people living with HIV, which creates an urgent need to optimize the diagnostic and treatment approach to the first-line or switch regimens. The use of dolutegravir plus a lamivudine two-drug regimen is one of the most promising solutions to ease the management of HIV treatment in this difficult period. In this review, we report the most salient features related to the use of this regimen from real-life cohorts, meta-analyses, randomized clinical trials, and studies presented at international conferences up to March 2021. We focused on the diagnostic and clinical-management implications of its use in real life, and how these comply with the contingent historical situation. The issue of the timing and type of diagnostic procedures and the relevance of classical diagnostic tests (such as genotype for resistance detection) is also discussed. According to the currently available results, dolutegravir plus a lamivudine two-drug regimen represents an outstanding tool, whose expected advantages fulfill the current requirements for optimal daily care of our HIV patients. Full article
(This article belongs to the Special Issue Diagnosis and Management of HIV Infection)
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