scholarly journals Reasons for immunologic inefficiency of antiretroviral therapy in patients with HIV

2014 ◽  
Vol 95 (4) ◽  
pp. 581-588 ◽  
Author(s):  
A F Oleynik ◽  
V Kh Fazylov

The main component of the treatment of patients with HIV infection is highly active antiretroviral therapy (HAART), which can help to control the disease. The main goal of HAART is to increase the life duration and to maintain the quality of patients’ life. Improved survival among HIV-infected patients receiving highly active antiretroviral therapy is achieved mainly by a decrease of HIV RNA viral load, which increases CD4 lymphocytes count. However, some patients may present with discordant response to treatment, when there is no CD4 lymphocyte count elevation associated with the virus disappearing from the blood. Such patients retain immunodeficiency, despite long-term treatment. The risk of opportunistic infections on the background of insufficient immunological response, despite viral replication suppression, is higher than in patients with good immunological response to treatment. Consistently low CD4 cell counts are associated with an increased risk of AIDS diagnosis. Furthermore, this group of patients shows a slight increase in mortality not associated with AIDS-defining illnesses. The reasons for the low CD4 lymphocytes count increase in some patients achieving virologic response to HAART remain unclear. The immunological efficacy of treatment depends on many factors: baseline CD4 count, duration of HIV infection prior to HAART initiation, age, co-infection with HCV, presence of secondary diseases and comorbidities, HAART regimens, IL-2 use and others. Literature review covers the phenomenon of immunological «non-response» to HAART, factors leading to its development, and possible methods of correction. Currently, there are more questions than answers in the area of immunological non-effectiveness of HAART in HIV-infected patients.

2009 ◽  
Vol 13 (2) ◽  
pp. 289-296 ◽  
Author(s):  
Anirban Chatterjee ◽  
Ronald J Bosch ◽  
Roland Kupka ◽  
David J Hunter ◽  
Gernard I Msamanga ◽  
...  

AbstractObjectivePredictors and consequences of childhood anaemia in settings with high HIV prevalence are not well known. The aims of the present study were to identify maternal and child predictors of anaemia among children born to HIV-infected women and to study the association between childhood anaemia and mortality.DesignProspective cohort study. Maternal characteristics during pregnancy and Hb measurements at 3-month intervals from birth were available for children. Information was also collected on malaria and HIV infection in the children, who were followed up for survival status until 24 months after birth.SettingDar es Salaam, Tanzania.SubjectsThe study sample consisted of 829 children born to HIV-positive women.ResultsAdvanced maternal clinical HIV disease (relative risk (RR) for stage ≥2 v. stage 1: 1·31, 95 % CI 1·14, 1·51) and low CD4 cell counts during pregnancy (RR for <350 cells/mm3v. ≥350 cells/mm3: 1·58, 95 % CI 1·05, 2·37) were associated with increased risk of anaemia among children. Birth weight <2500 g, preterm birth (<34 weeks), malaria parasitaemia and HIV infection in the children also increased the risk of anaemia. Fe-deficiency anaemia in children was an independent predictor of mortality in the first two years of life (hazard ratio 1·99, 95 % CI 1·06, 3·72).ConclusionsComprehensive care including highly active antiretroviral therapy to eligible HIV-infected women during pregnancy could reduce the burden of anaemia in children. Programmes for the prevention of mother-to-child transmission of HIV and antimalarial treatment to children could improve child survival in settings with high HIV prevalence.


2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Julie C. Gaardbo ◽  
Hans J. Hartling ◽  
Jan Gerstoft ◽  
Susanne D. Nielsen

Treatment of HIV-infected patients with highly active antiretroviral therapy (HAART) usually results in diminished viral replication, increasing CD4+ cell counts, a reversal of most immunological disturbances, and a reduction in risk of morbidity and mortality. However, approximately 20% of all HIV-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution. Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution in HIV infection, including mechanisms, relevance for clinical care, and possible solutions.


Author(s):  
E. V. Saidakova ◽  
◽  
L. B. Korolevskaya ◽  
V. V. Vlasova ◽  
◽  
...  

In HIV-positive patients, hepatitis C virus (HCV) coinfection is associated with the development of se-vere systemic inflammation and an increased risk of a discordant response to highly active antiretroviral therapy in which supressed viral replication doesn’t lead to effective CD4+ T-cell regeneration. At the same time, the data on the systemic inflammation in HIV/HCV coinfected patients with ineffective resto-ration of CD4+ T-cell counts during therapy are limited. The aim of this work was to characterize system-ic inflammation in HIV/HCV coinfected patients with a discordant response to treatment. We studied three groups: 1) HIV/HCV coinfected subjects with a discordant response to therapy (CD4+ T-cells less than 350/ul); 2) HIV/HCV coinfected patients with a standard response to therapy (CD4+ T-lymphocytes over 350/ul); 3) voluntary blood donors without HIV and HCV infections. Systemic inflammation indices were assessed by the content of proinflammatory and anti-inflammatory cytokines in blood plasma (eotax-in, IL-1β, IL-4, IL-5, IL-10, IL-13, MCP-1, MIP-1α, MIP-1β, IP-10 , TNFα, TGF-β1, TGF-β2), the levels of which were analyzed by multiplex and enzyme-linked immunosorbent assays. As a result it was shown that in HIV/HCV coinfected patients, therapeutically uncontrolled hepatitis C leads to the development of pronounced systemic inflammation, which is only slightly aggravated by a discordant response to highly active antiretroviral therapy.


Chemotherapy ◽  
2018 ◽  
Vol 63 (2) ◽  
pp. 64-75 ◽  
Author(s):  
Ornella Franzese ◽  
Maria Luisa Barbaccia ◽  
Enzo Bonmassar ◽  
Grazia Graziani

Since the introduction of highly active antiretroviral therapy more than 2 decades ago, HIV-related deaths have dramatically decreased and HIV infection has become a chronic disease. Due to the inability of antiretroviral drugs to eradicate the virus, treatment of HIV infection requires a systemic lifelong therapy. However, even when successfully treated, HIV patients still show increased incidence of age-associated co-morbidities compared with uninfected individuals. Virus- induced immunosenescence, a process characterized by a progressive decline of immune system function, contributes to the premature ageing observed in HIV patients. Although antiretroviral therapy has significantly improved both the quality and length of patient lives, the life expectancy of treated patients is still shorter compared with that of uninfected individuals. In particular, while antiretroviral therapy can contrast some features of HIV-associated immunosenescence, several anti-HIV agents may themselves contribute to other aspects of immune ageing. Moreover, older HIV patients tend to have a worse immunological response to the antiviral therapy. In this review we will examine the available evidence on the role of antiretroviral therapy in the control of the main features regulating immunosenescence.


Author(s):  
John Jospeh Diamond Princy ◽  
Kshetrimayum Birendra Singh ◽  
Ningthoujam Biplab ◽  
Ningthoukhongjam Reema ◽  
Rajesh Boini ◽  
...  

Abstract Introduction Human immunodeficiency virus (HIV) infection is a state of profound immunodeficiency. Disorders of hematopoietic system are a common but often overlooked complication of HIV infection. This can manifest at any stage of the disease but more commonly in the advanced stage with low CD4 count. Anemia is the most common hematological abnormality in HIV patients and prevalence ranges from 1.3 to 95%. As HIV disease progresses, the prevalence and severity of anemia also increase. Hence, this study was undertaken to assess the hematological parameters of HIV-infected patients on highly active antiretroviral therapy (HAART) at different treatment durations with the hope to improve the HAART outcome in HIV patients and its correlation with CD4 count. Methods This prospective longitudinal study enrolled 134 HIV-infected patients admitted to or attending the OPD in the Department of Medicine or Antiretroviral Therapy (ART) Center (Center of Excellence), Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, from 2018 to 2020. Complete hemogram, CD4 count, and other related-blood investigations were studied. Results The mean age of the study population was 39.9 ± 11.04 years. Of the 134 patients, 75 (56%) were males and 59 (44%) were females. Twelve (9%) patients had a history of injecting drug use (IDU). TLE (tenofovir, lamivudine, efavirenz) regimen was started on 112 (83.6%) patients and the majority of them (69/134 [51.5%]) had a CD4 count of 200 to 499 cells/mm3, which increased significantly 6 months after HAART to 99 to 1,149 cells/mm3, with a mean of 445 ± 217 cells/mm3. There were significant improvements in hemoglobin (Hb) levels, total leukocyte count (TLC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) after HAART indicating a positive correlation with CD4 count (p < 0.05). Thrombocytopenia was observed higher after HAART when compared to baseline. There was a positive correlation between platelet count and CD4 count. However, the mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR) had a negative correlation with CD4 count. Conclusion The study inferred a strong positive correlation between CD4 and Hb levels, TLC, ANC, ALC, and platelet count after HAART with improvement in these values as CD4 count increases. Specific treatment intervention based on the changes in the immunohematological profile trends can help prevent most of the adverse effects on HIV patients in our community.


2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Samad Rasul ◽  
Robert Delapenha ◽  
Faria Farhat ◽  
Jhansi Gajjala ◽  
Syeda Mehreen Zahra

Graves' disease after the initiation of highly active antiretroviral therapy (HAART) in certain HIV-1-infected individuals has been described as an immune reconstitution inflammatory syndrome (IRIS). This phenomenon should be suspected in individuals who present with clinical deterioration and a presentation suggestive of hyperthyroidism despite good virological and immunological response to HAART. Signs and symptoms of hyperthyroidism may be discrete or overt and typically develop 8–33 months after initiating therapy. One to two percent of HIV-infected patients can present with overt thyroid disease. Relatively few cases of Graves' IRIS have been reported in the literature to date. We describe four cases of Graves' IRIS in HIV-infected patients who were started on HAART therapy.


2001 ◽  
Vol 8 (5) ◽  
pp. 943-948 ◽  
Author(s):  
Vesna Blazevic ◽  
Shirley Jankelevich ◽  
Seth M. Steinberg ◽  
Freda Jacobsen ◽  
Robert Yarchoan ◽  
...  

ABSTRACT The present study analyzes the effect of highly active antiretroviral therapy (HAART) on restoration of cellular immunity in human immunodeficiency virus (HIV)-infected children over a 24-week period following initiation of HAART with ritonavir, nevirapine, and stavudine. The immunological parameters evaluated at four time points (at enrollment and at 4, 12, and 24 weeks of therapy) included cytokine production by monocytes as well as T-cell proliferation in response to mitogen, alloantigen, and recall antigens including HIV type 1 envelope peptides. Circulating levels of interleukin-16 (IL-16) were measured, in addition to CD4+ T-cell counts, plasma HIV RNA levels, and the delayed-type hypersensitivity (DTH) response. At enrollment the children exhibited defects in several immune parameters measured. Therapy increased CD4+ T-cell counts and decreased viral loads significantly. By contrast, the only immunological parameter that was significantly increased was IL-12 p70 production by monocytes; the DTH response to Candida albicans also showed a strong increase in patients becoming positive. In conclusion, these results demonstrate that HAART in HIV-infected children affects the dynamics of HIV replication and the CD4+ T-cell count over 24 weeks, similar to the pattern seen in HIV-infected adults. Furthermore, these data indicate improvement in antigen-presenting cell immunological function in HIV-infected children induced by HAART.


AIDS Care ◽  
2018 ◽  
Vol 31 (8) ◽  
pp. 913-922 ◽  
Author(s):  
Yuan-Yuan Wang ◽  
Yu Jin ◽  
Chang Chen ◽  
Wei Zheng ◽  
Shi-Bin Wang ◽  
...  

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