Successful Highly Active Antiretroviral Therapy Research Articles

Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy: an open-label, noncomparative study

Human immunodeficiency virus (HIV)+ patients have an increased risk of anogenital warts. High-risk (HR) human papillomaviruses (HPVs), especially types 16 and 18, are major risk factors for precancerous and cancerous lesions of the anogenital tract, while low-risk (LR) HPVs are associated with benign lesions. Cure of genital warts with ablative techniques, surgical excision, podophyllotoxin or trichloroacetic acid is frequently difficult. Treatment with imiquimod cream showed a total clearance of external genital or perianal warts in about 50% of immunocompetent subjects. However, total clearance was reduced in HIV+ subjects not treated with highly active antiretroviral therapy (HAART). To assess clinically and by monitoring HPV content the efficacy of 5% topical imiquimod to treat anogenital warts in HIV+ subjects with at least partially restored immune functions. Fifty HIV+ patients successfully treated with HAART (total CD4+ cells > or = 200 cells mm(-3) and plasma HIV RNA load < 10(4) copies mL(-1)) with anogenital warts were included. Imiquimod 5% cream was applied on external genital or perianal warts three times weekly for up to 16 weeks. Warts were tested at entry and after treatment for human LR- and HR-HPV DNA. Total wart clearance was observed in 16 of 50 (32%) patients at week 16. At enrolment, HPV DNA was present in more than 90% of lesions with a majority of lesions co-infected by HR- and LR-HPV. At study end, the HPV load decreased or became undetectable in 40% of cases studied. Imiquimod 5% cream did not show safety concerns and is suitable for use in HIV+ subjects with anogenital warts and successful HAART treatment.

Influence of repeated cycles of structured therapy interruption on the rate of recovery of CD4+ T cells after highly active antiretroviral therapy resumption

CD4+ T cell recovery dynamics were analysed during the 'on treatment' periods in structured therapy interruption (STI) as well as the long-term immune reconstitution with highly active antiretroviral therapy (HAART) after finishing STI. One hundred and twenty HIV-1-infected patients on successful HAART were randomized to receive for 2 years continuous HAART (n=37) or two different strategies of STI (n=83). After this period, most patients received continuous HAART for 2 years. During the STI period, the rate of recovery of CD4+ T cells decreased progressively from the first to the last resumption of HAART {median change of increase: +232 [interquartile range (IQR): +126, +318], +116 (IQR: +10, +471), +87 (IQR: -54, +252) and -26 (IQR: -352, +211) cells/mm3 after the first, second, third and fourth resumption, respectively}. After the STI period and 2 years of continuous HAART, the median CD4+ count remained significantly lower than at baseline in STI arms, both in the virological arm [559 (IQR: 383, 727) versus 771 (IQR: 625, 913) cells/mm3, P<0.0001] and the immunological arm [619 (IQR: 501, 789) versus 787 (IQR: 657, 954) cells/mm3, P<0.0001], but not in the control arm [886 (IQR: 564, 1122) versus 780 (IQR: 539, 945) cells/mm3, P=0.68]. In a multivariate analysis, the nadir of CD4+ T cells and the baseline value of CD4+ before the STI period independently predicted the level of CD4+ T cells 2 years after resumption of HAART (in both cases, P<0.0001). The drop in CD4+ cell count after a first and a second period of 3 months of interruption of HAART was completely recovered after resuming HAART; conversely, interruptions longer than 6 months were deleterious for the recovery of CD4+. CD4+ cell count did not rebound completely in patients who received 2 years of HAART after 2 years of STIs.

Episodes of low-level viral rebound in HIV-infected patients on antiretroviral therapy: frequency, predictors and outcome

The rate, predictors and outcome following episodes of low-level viral rebound (LLVR) in HIV patients on highly active antiretroviral therapy (HAART) are unknown. Retrospective assessment of all HIV patients who experienced LLVR episodes on HAART at one institution from January 1999 to December 2006. LLVR was defined as plasma HIV-RNA between 51 and 500 copies/mL after at least two consecutive undetectable plasma viral load measurements made during the last 6 months. Virological failure was defined as plasma HIV-RNA >500 copies/mL. Out of 2720 HIV patients on successful HAART during the 8 year study period, 779 (28.6%) developed at least one LLVR episode. Only 655 patients who kept unchanged their HAART regimen following LLVR episodes were further examined. After 12 weeks, undetectable viraemia was regained in 458 (71%), which were considered as blips. In contrast, 66 (9%) LLVR episodes were followed by virological failure, and drug resistance mutations developed in most cases, mainly rtM184V (66%) and rtK103N (29.5%). Plasma HIV-RNA remained between 51 and 500 copies/mL at 12 weeks in the remaining 131 (20%) patients with LLVR episodes. In the multivariate analysis, only plasma HIV-RNA levels at the time of LLVR predicted subsequent virological failure. Episodes of LLVR in HIV patients on successful HAART are relatively common and represent transient events (blips) in most cases (71%). Keeping the same treatment regimen, virological failure follows in <10% of the cases. Plasma HIV-RNA level at the time of LLVR is the best predictor of subsequent failure.

Decreased serum lipocalin-2 levels in human immunodeficiency virus-infected patients: increase during highly active anti-retroviral therapy

Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level <200 copies/ml after 24 months); (iv) phytohaemagglutinin-stimulated NGAL release in MNC cells from bone marrow aspirates was decreased in untreated HIV-infected patients compared with healthy controls, but increased after 26 weeks on HAART; and (v) there was a significant positive correlation between neutrophil counts and NGAL levels at all time-points during HAART. We have shown decreased NGAL levels in HIV-infected patients, potentially reflecting decreased number and function of neutrophils as well as impaired bone marrow myelopoiesis. These abnormalities were reversed by successful HAART. Our findings underscore further the involvement of neutrophils and innate immunity in HIV-related immunodeficiency.

Cytomegalovirus Retinitis and Immune Recovery Uveitis in AIDS Patients Treated with Highly Active Antiretroviral Therapy in Taiwanese

Purpose: To determine the characteristics of cytomegalovirus (CMV) retinitis and immune recovery uveitis (IRU) in the era of highly active antiretroviral therapy (HAART). Methods: We reviewed data from 47 of 79 consecutive patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis. Results: The incidence of CMV retinitis in AIDS patients has markedly decreased over the recent 10 years. The characteristics of CMV retinitis have changed. Development of IRU occurred in 24.4%. Conclusions: Symptomatic IRU develops in a significant number of patients with inactive CMV retinitis following successful HAART. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.

Microsocial Environmental Influences on Highly Active Antiretroviral Therapy Outcomes Among Active Injection Drug Users

Active injection drug users (IDUs) are at high risk of unsuccessful highly active antiretroviral therapy (HAART). We sought to identify baseline factors differentiating IDUs' treatment success versus treatment failure over time among those taking HAART. Interventions for Seropositive Injectors-Research and Evaluation (INSPIRE) study participants were assessed at baseline and at 6- and 12-month follow-ups. Multinominal regression determined baseline predictors of achieving or maintaining viral suppression relative to maintaining detectable viral loads over 12 months. Of 199 participants who were retained and remained on HAART, 133 (67%) had viral load change patterns included in the analysis. At follow-up, 66% maintained detectable viral loads and 15% achieved and 19% maintained viral suppression. Results indicated that those having informal care (instrumental or emotional support) were 4.6 times more likely to achieve or maintain viral suppression relative to experiencing treatment failure. Those who maintained viral suppression were 3.5 times less likely to live alone or to report social discomfort in taking HAART. Study results underscore the importance of microsocial factors of social network support, social isolation, and social stigma for successful HAART outcomes among IDUs. The findings suggest that adherence interventions for IDUs should promote existing informal HIV caregiving, living with supportive others, and positive medication-taking norms among social networks.

Short Communication:Comparative Longitudinal Studies of HERV-K and HIV-1 RNA Titers in HIV-1-Infected Patients Receiving Successful versus Unsuccessful Highly Active Antiretroviral Therapy

The viral kinetics of HERV-K in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) is not unknown. HERV-K kinetic modeling may provide insight into factors altering the effectiveness of HAART in suppressing HIV-1 burden. We conducted a longitudinal study measuring the HERV-K RNA titers in four patients with successful HIV-1-suppressive HAART and in six patients undergoing HAART failure. HERV-K titers were usually undetectable in patients with successful HAART, and when detected, HERV-K titers remained below 5000 copies/ml. On the other hand, HERV-K RNA was consistently detected in patients who failed to respond to HAART before and after HIV-1 rebounds (p < 0.001). Elevated HERV-K RNA titers frequently preceded HIV-1 rebounds. These results suggest that HERV-K viral load may predict HIV-1 reactivation. HERV-K RNA testing might be clinically useful in predicting the onset of HIV-1 resistance due to suboptimal antiretroviral drug levels and/or poor adherence to treatment.

Experiences and Perceptions of Patients with 100% Adherence to Highly Active Antiretroviral Therapy: A Qualitative Study

A decade has passed since the introduction of highly active antiretroviral therapy (HAART) as standard of care for HIV/AIDS patients. The success of HAART is largely dependent on almost 100% adherence to it. In this study our primary aim was to understand from patients' own perspectives and experiences what resulted in them having 100% adherence to HAART. Thus, we purposefully recruited for in-depth interviews 10 participants (7 men and 3 women) with 100% adherence to HAART (>/=6 months previous to the interviews). All interviews were transcribed verbatim and analyzed by using Giorgi's phenomenological analysis approach. The following issues emerged from the analysis: readiness to go on HAART; HAART viewed as a life-line; maintenance of 100% adherence related with willingness to live longer and healthier; optimal ongoing patient-physician relationship, better coping and/or lack of perceived side effects; and improvements in clinical condition as well as in CD4 T-cells count and viral load reinforced the motivation to continue 100% adherence. The study findings should be helpful for health professionals caring for HIV-infected individuals on HAART.

HIV-1 Associated Dementia In Pre And Post HAART Era

Patients infected with human immunodeficiency virus (HIV-1) invariably experience a wide range of neurological complications associated with AIDS that are collectively referred to as HIV associated dementia (HAD). HIV associated dementia usually develops in advanced stages of HIV-1 disease. Clinically HAD involves varying degree of neurological and psychiatric symptoms like – cognitive impairment, motor disturbances, hallucinations, delirium and behavioural changes, often leading to progressive deterioration of cognitive and motor skills. The worldwide incidence of HAD is up to 40% of AIDS population. The advent of highly active anti-retroviral therapy (HAART) had a significant negative impact on HAD, nevertheless neurological complications had shown persistence. Variability in drug penetration, distribution, drug resistance, optimal dosage levels and toxicity, hinder the success of HAART in countering the neuronal cell death or damages to the brain. In the post HAART period a subtle form of HAD has evolved which is referred as minor cognitive motor disorder (MCMD). Hence the HIV-1 induced neurological complications continue to be a clinical problem amongst AIDS affected individuals. The aim of this review is to describe the cellular and molecular basis of neuropathogenesis of HAD, list the most common therapeutic regimens used in HAART, discuss briefly the advantages and limitations of HAART agents and describe how HAD has evolved in post HAART era. doi: 10.5214/ans.0972.7531.2007.140204

Long-Term Suppression of HIV Infection: Benefits and Limitations of Current Treatment Options

HIV type 1, a causative agent of AIDS, is a source of worldwide morbidity and mortality. There are an estimated 1 million people in North America currently living with HIV infection, and more than 40,000 new cases occur annually. Before the advent of highly active antiretroviral therapy (HAART), the mortality rate of HIV infection was nearly 100%, and life expectancy was short. However, successful HAART delays the onset of AIDS, allowing patients to live with chronic HIV infection for 20 years or more. HAART usually consists of a combination of protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs). Although these agents are highly efficacious in delaying the onset of AIDS, their clinical utility is limited by viral resistance, nonadherence to therapy, and drug toxicity. Consequently, multidrug regimens are necessary for successful treatment. Initial NNRTI-based HAART regimens are effective at reducing viral load and boosting CD4(+) cell counts. NNRTI resistance is uncommon, but should it occur, the NNRTI-based therapy needs to be quickly replaced by a PI-based therapy. Triple NRTI-based regimens are recommended only if NNRTI- or PI-based regimens cannot be used. When developing a multidrug regimen, it is also important to select HAART agents with limited adverse effects. Because each HAART agent has its own unique adverse effect profile, selecting a regimen with a favorable profile may be difficult. For example, certain PIs produce adverse metabolic effects that may increase the risk of developing cardiovascular disease. In contrast, NNRTI-based therapies have a different side effect profile. Because each HAART agent has specific limitations, tailoring a regimen to the individual patient is of paramount importance for achieving optimal outcomes.

Strategies for Improving Patient Adherence to Therapy and Long-Term Patient Outcomes

Adherence to treatment regimens is essential to the success of highly active antiretroviral therapy (HAART) in patients infected with HIV. Multiple research studies have clearly demonstrated the close association between proper adherence to HAART and decreases in both plasma HIV RNA levels and HIV-associated mortality rates. In an effort to maintain virologic suppression, adherence levels of 95% are required for patients treated with HAART. However, community reports suggest that actual adherence levels are often far lower than those required for successful HAART; many studies show that 40% to 60% of patients are less than 90% adherent. Multiple reasons for nonadherence to HAART regimens have been reported by patients infected with HIV. Patients with mental illness (e.g., depression) are more than seven times more likely not to adhere to HAART regimens compared with patients without mental illness. Substance abuse is also a major barrier to adherence, with approximately 66% of HIV-infected intravenous drug users reporting suboptimal adherence to HAART regimens. Other barriers to adherence include uncertainty about both the effectiveness of treatment and the consequences of poor adherence, regimen complexity, side effects of treatment, and lack of social support. This article will discuss the strategies that should be used by all members of the multidisciplinary team treating patients with HIV/AIDS to encourage patient adherence to treatment. These strategies include educating and motivating patients, simplifying treatment regimens and tailoring them to individual lifestyles, preparing for and managing side effects, and addressing the concrete issues that may present barriers to adherence. In addition, adherence-boosting interventions that have established efficacy in controlled trials, such as motivational interviewing, and nurse-based interventions for patient populations with low health-literacy will be reviewed.

AIDS-Defining Illnesses: A Comparison Between Before and After Commencement of Highly Active Antiretroviral Therapy (HAART)

Attempts to address the significant impact of HAART on medical variables on the Malaysian HIV/AIDS population have yet to be evaluated. This study aims to analyze the proportions of AIDS-defining illnesses (ADIs) before and after HAART. A retrospective study was carried out on 128 new cases of HIV infected patients who first commenced HAART in 2004 at the national HIV reference center. Before commencement of HAART, 76 clinical episodes of ADIs were recorded in 52 patients. Most common being pulmonary Mycobacterium tuberculosis (28.9%), PCP (27.6%) and disseminated and extrapulmonary Mycobacterium tuberculosis (11.8%). During HAART, 8 clinical episodes of ADIs were documented in 7 patients with a median time of onset of 10 weeks after initiation of HAART (range, 4-36 weeks). The median CD4 count at the time of the commencement of HAART for these patients was 11 cells/mm(3). ADIs reported include PCP (2 episodes), disseminated and extrapulmonary Mycobacterium tuberculosis (2 episodes), extrapulmonary cryptococcosis (1 episode), esophageal candidiasis (1 episode), recurrent pneumonia (1 episode) and disseminated or extrapulmonary histoplasmosis (1 episode). Three (37.5%) of these occurred despite a reduction of viral load by at least 2 log(10) and an increased in the CD4 cell count. In conclusion, ADIs can still present after the initiation of successful HAART especially in those with CD4 counts below 100 cells/mm(3). In Malaysia, ADIs are the major causes of HIV/AIDS associated morbidity and mortality, thus increased awareness on the management of these illnesses is warranted especially in the months following HAART.

Reconstitution of Herpes Simplex Virus–Specific T Cell Immunity in HIV‐Infected Patients Receiving Highly Active Antiretroviral Therapy

Production of herpes simplex virus (HSV)-specific interferon- gamma by peripheral-blood mononuclear cells (PBMCs) of HSV-seropositive healthy donors and human immunodeficiency virus-infected persons was determined by use of ELISPOT. The mean +/- SD number of spot-forming cells/10(6) PBMCs was 314 +/- 74 in 11 healthy donors, 360 +/- 69 in 3 long-term nonprogressors (LTNPs), 186 +/- 52 in 9 newly diagnosed patients, and 181 +/- 59 in 33 patients who were receiving highly active antiretroviral therapy (HAART) for a median period of 30 months (range, 1-109 months). In 9 patients monitored prospectively while receiving virologically and immunologically successful first-line HAART, the number of spot-forming cells increased by 5.6/month (95% confidence interval, 1.2-9.9 [P=.01]) and 21.3/100 CD4 cells/mm(3) gained (95% confidence interval, 13.8-28.7 [P<.0001]). Responses were correlated with LTNP status and CD4 cell count.

Intracellular and plasma efavirenz concentrations in HIV-infected patients switching from successful protease inhibitor-based highly active antiretroviral therapy (HAART) to efavirenz-based HAART (SUSTIPHAR Study)

To assess intracellular and plasma efavirenz concentrations in HIV-infected patients who switched to efavirenz-based highly active antiretroviral therapy (HAART) from successful protease inhibitor-based HAART. A total of 49 patients were included in this observational cohort study. At inclusion, all patients had plasma HIV-RNA levels<50 copies/mL and switched to efavirenz combined with two nucleoside reverse transcriptase inhibitors. Intracellular and plasma concentrations were measured 12 h post-dose, 1 month (M1) and 6 months (M6) after starting efavirenz. Virological success (VS) was defined as plasma HIV-RNA level<50 copies/mL within the first 12 months and remaining undetectable at the end of the follow-up. VS was documented in 48 patients for at least 12 months (range 12-78 months). High inter-patient variabilities of intracellular and plasma efavirenz concentrations were observed (coefficients of variation>40%). At M1 and M6, respectively, median [Q1; Q3] intracellular efavirenz concentrations were 5300 [2830; 11 530] and 6790 [3870; 8790] ng/mL, median plasma efavirenz concentrations were 2050 [1600; 3100] and 2100 [1410; 2500] ng/mL. No correlation was found between intracellular and plasma concentrations. Plasma efavirenz levels exceeded the proposed threshold of 1000 ng/mL in 96% of patients from M1. For moderately pre-treated HIV-infected patients with few mutations who switched to efavirenz from previous successful HAART, the proposed plasma efficacy-threshold was reached without any dosage adaptation. VS was maintained beyond 12 months, despite high inter-patient and intra-patient variabilities of intracellular and plasma efavirenz concentrations.

Predictors of short-term success of antiretroviral therapy in HIV infection

The success of highly active antiretroviral therapy (HAART) in HIV infection may be influenced by numerous host factors. There is a lack of data presenting a combined assessment of a variety of these parameters for treatment efficacy in clinical routine practice. Different indices of therapeutic drug monitoring (TDM) were evaluated prospectively in the context of self-reported adherence, health-related quality of life and social determinants, as measured by a questionnaire. A total of 210 individuals were studied between 2002 and 2004, 77% were males, mean age was 44 years, mean CD4 count was 336 cells/mm3 and 63% had a viral load < 50 copies/mL. In univariate analysis, baseline viral load, unscheduled drug levels, a 4 h pharmacokinetic profile (PK-P) at a scheduled visit and self-reported complete adherence within the previous 2 weeks were significantly associated with virological success of HAART at 12 weeks. At 24 weeks, only baseline viral load, the 4 h PK-P and adherence were significantly associated with HAART efficacy. In multivariate analysis, baseline viral load, adherence, unscheduled drug levels, trough levels at a visit with appointment as well as the 4 h PK-P were significantly associated with virological success at 12 weeks. At 24 weeks, only adherence was significantly linked to outcome. The other parameters were not found to have an impact on treatment efficacy. TDM and self-reported adherence were independently predictive of short-term HAART success in this prospective study. Unscheduled drug measurements provided similar diagnostic information as a 4 h PK-P. Thus, we propose the use of unscheduled drug level monitoring and self-reported adherence to help identify patients with elevated risk of virological failure.

Failure to eradicate HIV despite fully successful HAART initiated in the first days of life

Highly active antiretroviral therapy (HAART) started shortly after birth resulted in reversion of human immunodeficiency virus (HIV) plasma viremia, proviral DNA in PBMC, viral culture, and serum HIV antibodies to negative. Discontinuation of HAART 2 years after apparent HIV eradication, however, was followed by virus replication, CD4 decline, and destruction of HIV-specific lymphocytes, epitomizing the impossibility of HIV eradication.

Better quality of life with neuropsychological improvement on HAART

BackgroundSuccessful highly active antiretroviral therapy (HAART) regimens have resulted in substantial improvements in the systemic health of HIV infected persons and increased survival times. Despite increased systemic health, the prevalence of minor HIV-associated cognitive impairment appears to be rising with increased longevity, and it remains to be seen what functional outcomes will result from these improvements. Cognitive impairment can dramatically impact functional ability and day-to-day productivity. We assessed the relationship of quality of life (QOL) and neuropsychological functioning with successful HAART treatment.MethodsIn a prospective longitudinal study, subjects were evaluated before instituting HAART (naïve) or before changing HAART regimens because current therapy failed to maintain suppression of plasma viral load (treatment failure). Subjects underwent detailed neuropsychological and neurological examinations, as well as psychological evaluation sensitive to possible confounds. Re-evaluation was performed six months after institution of the new HAART regimen and/or if plasma viral load indicated treatment failure. At each evaluation, subjects underwent ultrasensitive HIV RNA quantitative evaluation in both plasma and cerebrospinal fluid.ResultsHAART successes performed better than failures on measures exploring speed of mental processing (p < .02). HAART failure was significantly associated with increased self-reports of physical health complaints (p < .01) and substance abuse (p < .01). An interesting trend emerged, in which HAART failures endorsed greater levels of psychological and cognitive complaints (p = .06). Analysis between neuropsychological measures and QOL scores revealed significant correlation between QOL Total and processing speed (p < .05), as well as flexibility (p < .05).ConclusionOur study investigated the relationship between HIV-associated neurocognitive impairment and quality of life. HAART failures experienced slower psychomotor processing, and had increased self-reports of physical health complaints and substance abuse. Contrariwise, HAART successes experienced improved mental processing, demonstrating the impact of successful treatment on functioning. With increasing life expectancy for those who are HIV seropositive, it is important to measure cognitive functioning in relation to the actual QOL these individuals report. The study results have implications for the optimal management of HIV-infected persons. Specific support or intervention may be beneficial for those who have failed HAART in order to decrease substance abuse and increase overall physical health.

An overview of the human immunodeficiency virus featuring laboratory testing for drug resistance.

The human immunodeficiency virus (HIV) pandemic is unique in human history in its rapid spread, its persistence, and the depth of its impact. The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that approximately 65 million people have been infected with HIV since the beginning of the epidemic. During this time, approximately 25 million people have died from acquired immune deficiency syndrome AIDS. HIV-associated morbidity and mortality was substantially reduced during the last decade following the introduction of highly active antiretroviral therapy (HAART). In spite of the striking success of HAART in treating HIV infection, many patients experience treatment failure as genetic changes emerge in the virus leading to drug resistance. Laboratory testing for drug resistance in HIV strains is now used in combination with other methods to guide antiretroviral therapy. The purpose of this report is to review the background information on HIV with the focus on the problem of drug resistance and to describe the laboratory methods of testing for drug resistance in HIV strains.

CD4+T Cell Recovery beyond the First Year of Complete Suppression of Viral Replication during Highly Active Antiretroviral Therapy Is Not Influenced by CD8+T Cell Activation

CD38 expression on CD8(+) T cells was longitudinally assessed in 31 human immunodeficiency virus (HIV)-infected persons with undetectable plasma viremia who had undergone highly active antiretroviral therapy (HAART) for 12 months and were followed for a mean of 30 months thereafter. Overall, CD4(+)T cell counts increased during follow-up, whereas CD38 expression remained stable. However, a subset of patients showed declines in CD38 expression, and, conversely, another subset showed increases in CD38 expression. No association could be found between long-term gains in CD4(+) T cells and evolution of CD38 expression. Thus, activation of CD8(+) T cells does not seem to be associated with the extent of CD4(+) T cell recovery beyond the first year of successful HAART.

Switch from inhibitory to activating NKG2 receptor expression in HIV-1 infection: lack of reversion with highly active antiretroviral therapy

HIV-1 infection is characterized by increase in inhibitory receptors and loss of activating receptors on natural killer (NK) cells, resulting in loss of cell activity. Exceptionally, for an inhibitory receptor, the proportion of NK cells bearing CD94-NKG2A decreases during HIV-1 infection. It is not understood whether HIV-1 itself or other concomitant infections drive these changes. To investigate the relationship between HIV-1 viraemia and changes in C-type lectin-like receptor expression in NK cells and to investigate the effect of highly active antiretroviral therapy (HAART) on these changes. Three cohorts of patients were studied: (1) before, during and after treatment interruption in aviraemic and viraemic patients receiving HAART (n = 15); (2) HIV-1-positive treatment-naive individuals (n = 13); and (3) HIV-1-positive individuals receiving successful HAART for a minimum of 1 year without interruption (n = 11). Flow cytometry was used to study the expression of NKG2A before and after treatment interruption and to define expanded populations of NK cells in untreated and treated HIV-1-positive individuals. Assays were performed in vitro to assess the cytotoxicity of the expanded populations. Increases in plasma HIV-1 RNA during treatment interruption in aviraemic HAART-treated individuals did not influence the proportion of NK cells carrying the complex CD94-NKG2A. Loss of NKG2A NK cells corresponded to the dramatic expansion of a distinct population of cells expressing a functional activating CD94-NKG2C receptor with skewed expression of killer cell immunoglobulin-like receptor family and natural cytotoxicity receptors. Changes in the NK cell repertoire during HIV-1 infection were not a result of HIV-1 viraemia alone but resembled those associated with concomitant infections.