ANALYTICAL REVIEW
Current literature on malignant neoplasms (MNP) in HIV patients is reviewed. NMP attracted attention when the very first HIV cases were found in humans. After ART drugs and therapeutic regiments and preventive and therapeutic interventions against opportunistic infections have been introduced in HIV clinics, MNP become the main cause of grave HIV cases, poor prognosis and lethal outcomes. In the present paper, NMP epidemiology in Russia and worldwide is analyzed, and the pathogenesis and symptoms of and therapeutic and preventive approaches to the most important HIV-associated NMP are overviewed.
ДОКЛАДЫ
Human immunodeficiency virus infection results in decreases counts and compromised functions of T-cells and the associated immunodeficiency, opportunistic infections, and cancer. The paradox of HIV infection is that all this occurs upon the activation of the immune system, mainly inborn immunity, and increased production of cytokines leading to chronic systemic inflammation. The immune response to HIV is evoked immediately upon infection; however, it fails to eliminate HIV, partly because of the active resistance of HIV to host immunity. Antiretroviral therapy is able to suppress HIV replication to a minimum and to somewhat restore the immune system; however, in many patients this is associated with serious complication manifested as the immune reconstitution inflammatory syndrome, IRIS. Immunotherapy for HIV infection is meant to prevent HIV infection and spread by preventive and therapeutic vaccination, including passive vaccination with broad-specificity neutralizing monoclonal antibodies and the use of anti-chemokine drugs and to restore immunity and to mitigate complications.
Nonalcoholic fatty liver disease (NAFL) is the main cause of chronic liver pathologies in westernized countries. The prevalence of fatty hepatosis in HIV patients is about 30% and reaches 40–72% in HIV patients co-infected with HCV, depending on other risk factors, such as NRTI and PI use in ART. Therefore, NAFL diagnostics is warranted in patients with HV/HCV co-infection. Besides that, for patients having HIV, HCV and NAFL special therapeutic approaches are required to ensure body mass reduction, HCV treatment, and drug therapy for NAFL.
ORIGINAL STUDIES
To study the clinical manifestations of CNS lesions in HIV patients, to analyze relationships between the conditions of the immune system, the rate of HIV replication, and the clinical picture. Study groups included 128 HIV patients, which had blood CD4 cell counts below 350 L–1 and were eligible for antiretroviral therapy, 65 patients (Group 1) having no clinical manifestation of CNS involvement, and 63 patients having such manifestations. HIV viral loads in blood plasma and in the cerebrospinal fluid, and the features of blood lesions were determined. In 28,6% of cases, the lesions were associated with mixed infections. In Group 2, HIV viral load in the CSF was 13,2 times higher than in Group 1. In the blood, viral load was significantly higher than in the CSF. It is concluded that tests for HIV as well as and for agents of opportunistic infections in the CSF should be performed in patients with pronounced immunosuppression.
Increasing HIV-related mortality makes a significant negative impact on socioeconomic and demographic situation in the Russian Federation. The objective of the present study was to define the causes of death in severe and comorbid HIV cases. To this end, a retrospective analysis of 265 case histories of deceased HIV patients admitted in 2010–2014 to the in-patient hospital of Saint-Petersburg Center for Prevention and Control of AIDS and Infectious Diseases was carried out. Concomitant conditions were diagnosed based on the results of clinical, laboratory, and instrumental investigations and on anamnesis data. The analysis suggests that HIV was found for the first time upon admission in 16% of the cases. The severity of patients’ conditions was associated with the delayed admission to the hospital and with the presence of mixed infections and concomitant conditions. ART was prescribed to 193 patients who then received the therapy for one month to three years. Patients’ conditions were becoming progressively worse in the cases of discontinued ART or non-adherence to ART and of failur to provide preventive treatments for opportunistic infections and concomitant somatic conditions. The main causes of lethal outcomes at the advanced stages of HIV infection were comorbidities, including HIV + chronic viral hepatitis and/or tuberculosis, malignancy, neurological conditions, and drug abuse.
ОБМЕН ОПЫТОМ
Study objectives: Fine-tuning of techniques for HIV-1 isolation from HIV patient blood samples; developing a collection of primary HIV-1 isolates; and investigating the biological features of currently circulating genetic variants of HIV-1 subtypes A and B and of their recombinant form CRF63_02A1. These objectives are important for better knowing of HIV-1 biology and for monitoring the characteristics of the spreading HIV-1 variants. Materials and methods: PBMC were isolated by whole blood centrifuging at 325 g for 30 min in 1,077 to 1,080 g/mL Ficoll gradient (MP Biomedicals, USA) followed by two washings with RPMI-1640. Donor PBMC were stimulated in RPMI-1640. The culture fluid was sampled, tested for viral p24 protein, and cryopreserved. HIV-1 reproduction was assessed by the accumulation of the viral protein in culture medium using an ELISA kit provided by Vector Best (Russia). Viral DNA was isolated from HIV patient blood plasma using RealBest DeltaMag kits and RT-PCR MasterMix kits (Vector Brest, Russia) and PCR BioMaster HS-Tag PCI-Color kits (Bilabmix, Russia). HIV-1 isolated were characterized genetically by sequencing env and pol genes using BigDyeTerminatorv31 kits (USA). Sixty-seven infectious variants of HIV-1 subtype A and B recombinants CRF63_02A1 and CRF02AG strain have been isolated and characterized.
Study objective: To compare the effectiveness of two defined combinations of NRTI drugs, i.e. Abakavir + Lamivudine and Zidovudine + Lamivudine and using drugs having respective international nonproprietary names.
Materials and methods: Using the above defined drug combinations and the respective drugs were compared based on retrospective records of their effectiveness.
Results and discussion: ART was discontinued less often by patients who were treated with defined drug combinations compared with those treated with the respective drugs: 10,6% (Abakavir + Lamivudin) vs. 29,7% (Abakavir (INN) and Lamivudine (INN)) and 17,3% (Zidovudin + Lamivudine) vs. 26,5 (Zidovudin (INN) and Lamivudine (INN)). Non-detectable viral loads were achieved more often by patients who were treated with defined drug combinations compared with those treated with the respective drugs: 80% (Abakavir + Lamivudin) vs. 72,8% (Abakavir (INN) and Lamivudine (INN)) and 72,1% (Zidovudin + Lamivudine) vs. 67,7% (Zidovudin (INN) and Lamivudine (INN)).
EPIDEMIOLOGY
The aim of study was to evaluate the molecular structure of the epidemiological and drug-resistant HIV-1 variants in patients with ART failure in Veliky Novgorod. Patients’ blood plasma (n=25) with HIV infection from Veliky Novgorod were used, aimed at identifying drug resistant viruses due to ART failure. Determination of subtypes of HIV-1 was performed by nucleotide sequence analysis of polymerase gene (pol) length of 1285 nt, protease encoding (PR) 465 nt in length and the reverse transcriptase (RT) gene portion length of 820 nt. Isolates phylogenetic analysis indicates that the predominant HIV-1 subtype A1 (96%) in the studied group of patients, which is the most common form of HIV-1 in Russia, and only one sample is a recombinant form of CRF_03 AB (4%). In 66,7% of men and 60% of women with HIV infection was first detected at the age of 30, which reflects the characteristics of the epidemic in recent years in the Russian Federation. When evaluating drug resistance mutations in only 56% of patients mutations of resistance to any drugs were identified. Nucleoside reverse transcriptase inhibitors resistance mutations were detected in 85,7% (48% of the group in total), non-nucleoside reverse transcriptase inhibitors resistance mutations were detected in 78,57% (44% of the group in total), protease inhibitors resistance mutations were detected in 21,42% (12% of the group). Molecular genetic analysis confirms the high virus homogeneity on the territory of the Russian Federation, however, reveals evidence of clustering multiple independent episodes of the virus penetration in the injecting drug users population in Novgorod region.
The official statistical data of HIV Registry filed at Regional Center for Prevention and Control of AIDS and infectious Diseases were used in assessing the time course of HIV epidemic in Primorkiy Region to define the region-specific features of the development of HIV epidemic in 2011–2016. HIV prevalence is increasing in the Region since 2011. Although the importance of the sexual route of HIV transmission is on the rise, the main route is still injection drug use. Trends in changes in the gender and age structure of HIV-infected population are defined. The highest HIV prevalence is found among males aged 25 to 49 years: 1113.4 per 100 000 male population, almost three times higher than the average value.