Intensive Antiretroviral Therapy Research Articles

Clinical characteristics of cervical cancer in patients infected with human immunodeficiency virus

Background. Infection caused by human immunodeficiency virus (HIV) is a slowly developing anthroponosis with a long course and a variety of clinical manifestations, which finally results in acquired immunodeficiency syndrome (AIDS). Over the past 4 decades, the HIV / AIDS pandemic has been considered as one of the world’s most serious public health problems. Globally, there were approximately 38 million people living with HIV in 2022; 53 % of them were women. The number of HIV-infected patients living in Russia reaches 1,168,000. The incidence and prevalence of HIV infectionvaries across different regions of Russia. High prevalence of cervical cancer usually correlates with HIV prevalence, which is associated with the long-term and aggressive persistence of human papillomavirus (HPV) in HIV patients. HIV co-infection is believed to be the main risk factor for HPV-related precancerous lesions to the cervical epithelium and their rapid progression to invasive cancer. Aim. To analyze risk factors for poor prognosis in HIV-infected patients with HPV. Materials and methods. This study included 15 HIV-infected patients with cervical cancer treated in Novosibirsk Regional Clinical Oncology Dispensary or Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of Russia between 2016 and 2021. Results. Median age of the patients was 38 years; all of them were HPV-positive. Their viral load was >400 copies / mL and baseline CD4+ cell count ≥350 cells / mL. All patients were diagnosed with AIDS, given the presence of HPV infection. During the therapy for cervical cancer, patients also received combination antiretroviral treatment, including Lamivudine Advanced at a dose of 300 mg / day. Ten patients received comprehensive treatment, while 8 patients received chemoradiotherapy. Conclusion. Given the more aggressive course of cervical cancer in HIV-infected patients, their treatment plan should be developed by a multidisciplinary team, including an infectious disease specialist, clinical pharmacologist, radiotherapist, and gynecological oncologist. Such patients should receive maximal antitumor treatment, as well as intensive antiretroviral therapy. HIV-positive women with cervical cancer require special attention to ensure treatment completion and to optimize long-term outcomes.

A Diffuse Large B cell Lymphoma (DLBCL) With Central Nervous System Involvement in a HIV Positive Patient

A Diffuse Large B cell Lymphoma (DLBCL) With Central Nervous System Involvement in a HIV Positive Patient We present a case of a 18-year-old woman hospitalized in the Clinic of Hematology of Craiova (Romania) in September 2010 for a diffuse large B cell lymphoma-HIV associated, treated with intensive antiretroviral therapy (HAART) and eight cycles of rituximab-CHOP, with a good response (complete remission). After eighteen months, the patient relapsed in the central nervous system and develops a depressive syndrome. Central nervous system involvement is frequent in patients with secondary malignant lymphoma-HIV associated and may be expressed as neurological symptoms and psychiatric manifestations.

Control of HIV latency by epigenetic and non-epigenetic mechanisms.

Intensive antiretroviral therapy successfully suppresses viral replication but is unable to eradicate the virus. HIV persists in a small number of resting memory T cells where HIV has been transcriptionally silenced. This review will focus on recent insights into the HIV transcriptional control mechanisms that provide the biochemical basis for understanding latency. There are no specific repressors of HIV transcription encoded by the virus, instead latency arises when the regulatory feedback mechanism driven by HIV Tat expression is disrupted. Small changes in transcriptional initiation, induced by epigenetic silencing, lead to profound restrictions in Tat levels and force the entry of proviruses into latency. In resting memory T cells, which carry the bulk of the latent viral pool, additional restrictions, especially the limiting cellular levels of the essential Tat cofactor P-TEFb and the transcription initiation factors NF-κB and NFAT ensure that the provirus remains silenced unless the host cell is activated. The detailed understanding of HIV transcription is providing a framework for devising new therapeutic strategies designed to purge the latent viral pool. Importantly, the recognition that there are multiple restrictions imposed on latent proviruses suggest that proviral reactivation will not be achieved when only a single reactivation step is targeted and that any optimal activation strategy will require both removal of epigenetic blocks and the activation of P-TEFb.

Attacking HIV Provirus: Therapeutic Strategies to Disrupt Persistent Infection

The therapeutic armamentarium for human immunodeficiency virus type 1 (HIV-1) infection continues to expand. New targets such as entry and integration have recently been successfully exploited. However, HIV-infected patients in need of treatment are currently committed to lifelong suppressive therapy. The persistence of integrated HIV DNA genomes capable of producing virus is a fundamental obstacle to the eradication or cure of HIV infection. Rational molecular or pharmacologic strategies to eliminate persistent HIV proviral genomes are an unaddressed therapeutic need. Coupled with potent antiretroviral therapy, treatments that could efficiently deplete the persistent DNA reservoir of HIV could radically alter treatment paradigms. Prior attempts to target persistent proviral infection deployed intensive antiretroviral therapy (ART) in combination with global inducers of T-cell activation. Initial trials of this approach were unsuccessful. Non-specific T-cell activation may induce high-level viral replication above a level that can be fully contained by ART, while increasing the susceptibility of uninfected cells. Selective targeting of HIV provirus via agents that induce the expression of quiescent HIV, but have limited effects on the uninfected host cell is an alternate approach to attack latent HIV. Recent studies define the role of repressive chromatin structure in maintaining HIV quiescence, and suggest that mechanisms that remodel chromatin about the HIV promoter are a possible therapeutic target. Other studies have uncovered specific factors that may act to induce or maintain latency by limiting the efficiency of HIV gene expression. Attempts to deplete latent HIV using drugs that alter chromatin structure have entered clinical study.

Attacking latent HIV provirus: from mechanism to therapeutic strategies.

The persistence of small population integrated proviral HIV genomes capable of expressing HIV within long-lived CD4 T cells is a fundamental obstacle to the eradication or cure of HIV infection. As potent antiretroviral therapy by itself appears to be an impractical approach to the eradication of this quiescent reservoir of HIV infection, new approaches are required. Initial studies failed to demonstrate that simultaneous, intensive antiretroviral therapy in combination with global inducers of CD4 T-cell activation could eradicate HIV infection. Global T-cell activation may induce viral replication and increase the number of susceptible uninfected target cells beyond the threshold that can be contained by current antiretroviral therapy. Future advances in antiretroviral therapy may, however, change this equation. An alternative approach to overcoming HIV latency is to develop agents capable of inducing the expression of quiescent HIV without enhancing de novo infection. More selective, targeted approaches may avoid the undesirable consequences of viral induction via signals that result in parallel T-cell activation. Such approaches using the cytokine IL 7, the novel protein kinase agonist prostratin, and inhibitors of the chromatin remodeling enzyme histone deacetylase have recently entered advanced preclinical and clinical testing. Many obstacles to the eradication of HIV infection exist. Encouraging advances in practical, targeted approaches to the major reservoir of persistence within resting CD4 T cells are, however, beginning to enter clinical testing.

Reversible Right Ventricular Dysfunction in Patients with HIV Infection.

Human immunodeficiency virus-related cardiomyopathy is characterized by global left ventricular (LV) dysfunction commonly associated with biventricular dilation. Human immunodeficiency virus (HIV) cardiomyopathy carries a poor prognosis, and the role of antiretroviral therapy in the reversal of heart failure is not very clear. We report two patients with HIV infection who presented with severe right ventricular (RV) dysfunction in the absence of pulmonary parenchymal, pulmonary arterial and left ventricular myocardial involvement. During the period of intensive antiretroviral therapy, the symptoms of right heart failure progressively and remarkably improved. This was accompanied by normalization of right ventricular size and RV function documented by repeat echocardiograms. Given that the serologic tests for opportunistic infections were negative, and the RV function improvement correlated with a decrement in the viral load, it is likely that the cardiomyopathy was due to direct infection by HIV. These cases illustrate that there can be isolated involvement of the right heart in the absence of lung, significant pulmonary vascular and left ventricular disease, and also that the antiretroviral therapy might reverse the cardiomyopathy.

Decline of CD3-positive T-cell counts by 6 months of age is associated with rapid disease progression in HIV-1–infected infants

Because HIV-1 infected infants with rapid progression (RP) of disease might benefit from early and intense antiretroviral therapy, the identification of predictive factors of RP becomes extremely important. Currently, the best predictive factors of RP in HIV-1 infected children are HIV-1 RNA levels and CD4-positive T-cell counts. A decrease in CD3-positive T-cell count has been identified as a predictive factor of AIDS development in HIV-1 infected adults. Our objective was to evaluate decreased number of CD3-positive T-cells as a predictive factor of RP in infants. Peripheral blood lymphocytes from HIV-1 infected infants (up to 6 months of age) were analyzed for an association of lymphocyte subsets with RP, which was defined as the occurrence of AIDS or death before 18 months of age. In infants with RP (n = 32), CD3-positive T-cell counts were 3093 cells/μL at <1 month of age, 3092 cells/μL at 1 to 3 months, and 2062 cells/μL at 3 to 6 months. Non-RP infants (n = 49) maintained their CD3-positive T-cells counts at approximately 4000 cells/μL for at least 6 months of life. CD3-positive and CD4-positive T-cell counts were significantly associated with RP. Our results suggest that a decreased CD3-positive T-cell count may be used to predict RP in HIV-1 infected infants (RR = 2.16, P = .001). (J Allergy Clin Immunol 2001;108:265-8.)

HIV treatment: where are we now?

The widespread use of highly active anti-retroviral therapy (HAART) since the summer of 1996 has brought many changes to the outlook and care of HIV positive clients and service provision. The routine use of increasingly intensive anti-retroviral therapies has resulted directly in dramatic declines in morbidity and mortality among HIV-infected patients with advanced immune depletion (Palella et al, 1998).

Palliative care and AIDS: 2 – Gastrointestinal symptoms

With the use of more intensive antiretroviral therapies (highly-active antiretroviral therapy, HAART) particularly in first world countries, reductions in the mortality and morbidity of HIV infection are being seen. However, though the prevalence of symptoms may change, symptom control does continue to be a problem for many people with HIV, particularly as their disease progresses. This is the second of 2 CME articles about palliative care and HIV infection. The first gave a background to palliative care, and covered symptom control of pain. This article gives suggestions for the treatment of common gastrointestinal symptoms in HIV infection; nausea and vomiting, cachexia and anorexia and chronic diarrhoea.

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.

National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.

Successful treatment of disseminated Mycobacterium simiae infection in AIDS patients.

Mycobacterium simiae is rarely isolated in clinical settings of non-HIV-infected patients. Isolation of M. simiae from clinical specimens in clusters has been limited to some parts of the world that include Israel, Cuba and the southern USA, mainly Texas. Only 8 patients with HIV and disseminated M. simiae infection have been previously described in the English literature. Successful treatment of disseminated M. simiae infection has never been reported and 6 of the cases have died within 8 months of diagnosis. We reviewed retrospectively the medical records of HIV-infected patients who had positive blood or bone marrow cultures for M. simiae at the Sheba Medical Center, Tel-Hashomer, Israel, between January 1992 and December 1996. A case of disseminated M. simiae infection was defined as isolation of M. simiae in blood or bone marrow culture in an HIV-infected patient with a compatible, otherwise unexplained, systemic disease. Mycobacterium simiae was isolated in blood and/or bone marrow cultures from 3 HIV-infected patients during the last 5 y. We describe the first successful treatment in AIDS patients with disseminated M. simiae infection. The patients are alive and well 20 months after instituting a combination of 3 antimycobacterial agents, clarithromycin, ethambutol and ciprofloxacin and intensive antiretroviral therapy.

Combination antiretroviral chemotherapy

There has been considerable interest and controversy over the potential clinical role of combination antiretroviral therapy, primarily in the treatment of patients with established HIV infection. In order to model the hematologic toxicity of high-dose combination antiretroviral therapy, the HL60 myeloid leukemia cell line was exposed to zidovudine, dideoxycytidine and/or didanosine. The results suggest that the myelotoxicity of high-dose combination antiretroviral therapy may be controlled by using very brief periods of drug exposure. Brief intense antiretroviral therapy may offer a useful approach, particularly in the treatment of patients with AIDS-related neoplasms who are also receiving myelotoxic antineoplastic drugs.