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PubMed2005

Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand's National Access to Antiretroviral Program.

BACKGROUND: Programs for access to antiretroviral treatment were only recently implemented in developing countries. This study aimed to describe the effect of highly active antiretroviral therapy (HAART) in treating human immunodeficiency virus (HIV)-infected children in Thailand's National Access to Antiretroviral Program for People Living with HIV/AIDS. METHODS: From August 2002 to July 2003, a total of 107 children were enrolled in the study. They received HAART consisting of either nevirapine or efavirenz, together with lamivudine and stavudine. Generic drugs and/or adult formulations were used. CD4 lymphocyte count, plasma HIV RNA level, and weight-for-age and height-for-age z scores were measured before, 2 months after, and every 6 months after initiation of HAART. A genotypic resistance assay was performed for patients with poor virological response. RESULTS: The mean age of the patients was 7.7 years (range, 2.1-13.8 years). At baseline, the median CD4 cell percentage was 3%, and the plasma HIV RNA level was 5.4 log10 copies/mL. Four patients died from HIV-related illness. After 72 weeks of HAART, the median CD4 cell percentage was 21%, and 76% of patients had HIV RNA levels of < 50 copies/mL. The mean weight-for-age and height-for-age z scores increased from -1.9 to -1.3 (P < .0001) and from -2.3 to -2.0 (P < .0001), respectively. The percentage of patients who took > or = 95% of prescribed medications during the interval between every follow-up visit was 86% For patients with suboptimal virological response, the most common resistance mutations among HIV isolates were associated with lamivudine and with nonnucleoside reverse-transcriptase inhibitors. CONCLUSION: In this resource-limited setting, HAART is safe and effective for HIV-infected children despite initiation of treatment during the advanced stage of disease. The use of generic and nonpediatric drug formulations is feasible.

Adolescent↗

PubMed2000

HAART and Mycobacterium avium complex in an HIV infected patient with severe factor VII deficiency.

A clinical syndrome represented by the association of Mycobacterium avium complex (MAC) infection with initiation of highly active antiretroviral therapy (HAART) has been recently described in patients with advanced HIV disease. HAART-associated improvement of the immune status might convert a clinically silent MAC infection into an active mycobacterial disease. A 40-year-old man with severe factor VII deficiency, advanced HIV-1 disease, a CD4 + lymphocyte count of 15 cells microL-1 (CDC stage A3) and 470,000 HIV-RNA copies mL-1 (measurement by NASBA system) underwent standard HAART (lamivudine, stavudine and ritonavir). Two weeks after HAART onset, the patient developed enlargement of the lymph nodes throughout the mesentery and after seven weeks a rapidly enlarging mass on the left side of the neck. Culture from a needle aspirate specimen revealed MAC. His CD4 + count had increased to 97 cells microL-1 and viraemia dropped to undetectable HIV-RNA copies. While continuing antiviral therapy, multidrug therapy for MAC infection (clarithromycin, ciprofloxacin, ethambutol, amikacin) was started with progressive improvement and cure of the neck mycobacterial infection and disappearance of the abdominal lymph nodes. HAART has been shown to offer significant clinical and laboratory benefits in terms of HIV disease with limited side-effects in Haemophiliacs. However, the clinical manifestation of an opportunistic infection should be mentioned as a possible complication of HAART in these patients, as well as in other categories of HIV infected patients, and in patients with congenital coagulopathies.

AIDS-Related Opportunistic Infections↗

PubMed2000

Sarcoidosis after antiretroviral therapy in a patient with acquired immunodeficiency syndrome.

A 53-year-old man with acquired immunodeficiency syndrome (AIDS) developed clinical and radiological features compatible with sarcoidosis 14 months after starting highly active antiretroviral therapy (HAART). The CD4 lymphocyte count had increased from 5 cells/mm(3) to 235 cells/mm(3) with HAART. Transbronchial lung biopsy showed nonnecrotizing granulomas. All studies for an infectious etiology were negative. His condition improved after treatment with corticosteroids. To our knowledge, this is the fifth case report of sarcoidosis occurring after initiation of antiretroviral therapy for AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Evaluation of secular trends in CD4+ lymphocyte loss among human immunodeficiency virus type 1 (HIV-1)-infected men with known dates of seroconversion.

The rate at which immunodeficiency develops in untreated human immunodeficiency virus type 1(HIV-1)-infected persons might be increasing or decreasing over time because of viral evolution or other factors. Beginning in 1984, Multicenter AIDS Cohort Study investigators recruited HIV-1-seronegative homosexual/bisexual men from four US metropolitan areas and examined them semiannually for HIV-1 seroconversion. To assess possible secular changes in the natural history of HIV-1 infection, the authors examined CD4+ lymphocyte data from 354 men who seroconverted between 1984 and 1991. To control for measurement differences among centers and over time, the authors adjusted CD4+ lymphocyte values to those of persistently seronegative participants. CD4+ lymphocyte percentage measurements at the first seropositive visit formed a U-shaped pattern, with the lowest values observed in 1988 and 1989. The authors observed no consistent secular pattern of CD4+ percentages at later visit dates, except that mean CD4+ percentages were consistently lowest in men who seroconverted in 1988. In a proportional hazards model, the time to the adjusted CD4+ lymphocyte count of < 500 cells/mm3 was not associated with the secular time of seroconversion (relative hazard = 1.05, 95% confidence interval 0.97-1.13). The authors' data do not suggest a major change in the natural history of HIV-1 infection of this population.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users.

To assess the effect of human immunodeficiency virus (HIV) immunosuppression on ongoing hepatitis C virus (HCV) infection, CD4 lymphocyte counts and serum concentrations of HCV RNA, HIV RNA, and alanine aminotransferase (ALT) were evaluated among members of a cohort of injecting drug users (IDUs). With 100 participants randomly selected at various stages of HIV-related immunosuppression, serum HCV RNA concentrations increased with age (P = .007) and were higher in HIV-positive IDUs with 201-500 (P = .026) and 51-200 (P = .004) CD4 cells/mL than in HIV-negative participants. Among 27 HCV-infected IDUs who acquired HIV infection, serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs, increasing by 0.60 logs after HIV seroconversion (P < .0001), by 0.12 logs each subsequent year (P = .006), and by 0.36 logs per log increase in CD4 cells (P = .01). Serum ALT levels were similar between HIV-positive (40.1 IU/mL) and HIV-negative (45.4 IU/mL) patients (P > .10). While HIV infection and possibly HIV progression are associated with increased HCV RNA levels, other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons.

Adolescent↗

PubMed1995

Effects of primary HIV-1 infection on subsets of CD4+ and CD8+ T lymphocytes.

OBJECTIVE: To analyse changes in T-lymphocyte subsets in patients with primary HIV infection and to determine their specificity (and therefore their diagnostic utility) by comparing these changes with those seen in other acute illnesses as well as in HIV-uninfected patients. METHODS: T-lymphocyte subsets were analysed by two- and three-colour flow cytometry, and compared between HIV seroconverters (n = 16), HIV-infected (n = 18) and uninfected (n = 33) controls, patients with infectious mononucleosis (n = 7), and patients suspected clinically of having primary HIV infection but who were later found to be uninfected (referred to as HIV non-converters; n = 17). RESULTS: CD4+ lymphocyte counts were significantly lower in HIV seroconverters (mean, 444 x 10(6)/l) than in the HIV non-converters (793 x 10(6)/l; P = 0.003), HIV-seronegative controls (888 x 10(6)/l; P < 0.0001) and, to a lesser extent, those with mononucleosis (694 x 10(6)/l; P = 0.045). The reduction in CD4+ lymphocytes occurred in both the CD45RA+ (55%) and CD45R0+ (33%) subsets. CD8+ lymphocyte counts were significantly higher in HIV seroconverters (942 x 10(6)/l) than in HIV non-converters (570 x 10(6)/l; P = 0.003) and seronegative controls (467 x 10(6)/l; P < 0.0001), but significantly lower than in the mononucleosis group (3682 x 10(6)/l; P = 0.004). The CD8+ cells in the HIV seroconverters had increased coexpression of CD45R0, human leukocyte antigen (HLA)-DR, CD38 and CD11a/CD18. The mean CD4: CD8 ratio in the HIV seroconverters was 0.49, versus 1.52 in the non-converters (P < 0.0001), 2.08 in the seronegative patients (P < 0.0001) and 0.37 in the mononucleosis patients (P > 0.2). CONCLUSIONS: Primary HIV infection is characterized by a depletion of CD4+ lymphocytes, especially of the CD45RA+ phenotype, and by an increase in CD8+ lymphocytes with an activated phenotype; the latter was also seen in patients with infectious mononucleosis but not in HIV non-converters or HIV-seronegative patients. Patients suspected clinically of having primary HIV infection but with normal T-cell phenotype are less likely to have primary HIV infection. These phenotypic changes, as well as an inverted CD4: CD8 ratio, can readily distinguish patients with primary HIV infection from HIV-uninfected patients except those with infectious mononucleosis. Therefore, T-cell-subset enumeration may be useful in the diagnosis of primary HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Idiopathic CD4+ lymphocytopenia and juvenile laryngeal papillomatosis.

We report on an association of idiopathic CD4+ lymphocytopenia (ICL) and juvenile laryngeal papillomatosis (JLP) in a pediatric-aged patient. Because of a past medical history of recurrent lung infections and severe chickenpox in infancy, immunologic investigations were done at age 6 years. On several occasions, a CD4+lymphocyte count of <300 cells/mm3 was detected, supporting the diagnosis of ICL. During follow-up, both medical (interferon-alpha) and surgical treatments of JLP were only partially efficient. Our patient developed disseminated infection with Mycobacterium avium and died at 10 years of age. Human papillomavirus is an important pathogen in pediatric and adult patients with ICL. In pediatric patients with JLP who develop other unusually severe viral or opportunistic infections, immunological investigations should be considered.

Antibodies, Viral↗

PubMed1995

The incidence of complications after caesarean section in 156 HIV-positive women.

OBJECTIVE: To investigate the risks of post-operative complications in HIV-positive mothers who undergo a caesarean section (CS) because the delivery cannot be safely accomplished by the vaginal route or to protect the infant from viral infection. DESIGN: In a multicentre study, we reviewed the incidence and type of post-operative complications in 156 HIV-positive women who underwent a CS. These results were compared with those observed in an equal number of HIV-uninfected women who matched for the indication requiring a caesarean delivery, the stage of labour, the integrity or rupture of membranes, and the use of antibiotic prophylaxis. SETTING: Seven teaching hospitals providing obstetrical care for mothers infected with HIV. RESULTS: We found that six HIV-infected mothers suffered a major complication (two cases of pneumonia, one pleural effusion, two severe anaemia and one sepsis) compared with only one HIV-negative woman who required blood transfusion after surgery. Minor complications like post-operative fever, endometritis, wound and urinary tract infections were significantly more frequent in HIV-positive women than controls. Multivariate analysis revealed that in HIV-infected women the only factor associated with a significant increase in the rate of complications was a CD4 lymphocyte count < 200 x 10(6)/l. CONCLUSIONS: The results of our study indicate that HIV-positive mothers are at an increased risk of post-operative complications when delivered by CS. The risk of post-operative complications is higher in HIV-infected women who are severely immunodepressed.

CD4 Lymphocyte Count↗

PubMedDate not supplied

[AIDS-associated meningeal cryptococcosis in the Hospital Diego Paroissien from 1996-1999].

A total of 148 patients with a diagnosis of HIV infection were studied in order to evaluate the incidence of meningeal cryptococcosis, including epidemic, immunologic and diagnostic characteristics. The diagnosis of cryptococcosis was carried out by direct examination with India ink and culture in Sabouraud agar of CSF in 28 patients (93.3%) and by blood cultures (lysis-centrifugation) in 2 patients (6.6%). All the isolated strains were identified as Cryptococcus neoformans. The incidence was 20.3% (30 patients). The preponderant risk behavior was endovenous drug addiction, and it was observed in 18 patients (60%). The symptomatology that prevailed was headache (87%). The median age was 28 years. At diagnosis, the immunologic impairment was severe (CD4+ lymphocyte count < 200) in 90% of patients. We found that 86.7% of patients had not completed their primary studies and only 13.3% had completed secondary studies. Although the acute mortality was high (36.7%), it was observed that all the patients who survived (24%) had been treated with anti-retroviral drugs.

AIDS-Related Opportunistic Infections↗

PubMed2003

Longitudinal study of mucosal Candida species colonization and candidiasis among human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

Acquisition and loss rates and estimates of duration of oral and vaginal Candida species colonization and candidiasis were examined among 868 human immunodeficiency virus (HIV)-seropositive and 437 at-risk HIV-seronegative women monitored prospectively during 1993-1999. Colonization and candidiasis acquisition rates, both oral and vaginal, were significantly higher among HIV-seropositive women; the magnitude of increase in candidiasis outcomes for HIV-seropositive women was greater for oral candidiasis than for vaginal candidiasis. Loss rates and estimates of duration of incident outcomes indicated that persistent mucosal colonization was more likely among HIV-seropositive women. However, results did not suggest persistent mucosal candidiasis. Higher HIV loads were significantly associated with increased odds of incident or persistent oral and vaginal colonization and candidiasis, an effect significantly reduced by highly active antiretroviral therapy for the incident outcomes of oral candidiasis and vaginal colonization. Cell-mediated immunodeficiency (CD4(+) lymphocyte count <500 cells/mm(3)) was significantly associated with increased odds of oral colonization or candidiasis, but not with vaginal colonization or candidiasis. In HIV-seropositive women, mucosal candidiasis is the consequence of multiple interacting factors.

AIDS-Related Opportunistic Infections↗

PubMed1999

[The level of triglycerides, total cholesterol and HDL cholesterol in various stages of human immunodeficiency virus (HIV) infection].

In 63 HIV-infected individuals the levels of concentration plasma triglicerides, total cholesterol and HDL cholesterol were determined by the level of immunological deficiency defined according to the CD4 lymphocytes count. The analyzed markers of lipid disorder allow to draw the following conclusions: 1. Along with the increase of immunological deficiency and clinical development of the HIV infection the disorders, which are indicated by the increase in trigliceride levels and decreased plasma concentrations for HDL cholesterol, intensify as well. 2. HIV-infected persons, particularly those treated with protease inhibitors, should have carefully monitored lipid metabolism.

Adult↗

PubMed2000

Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Adult AIDS Clinical Trials Group 285 Study Team.

Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1-infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 microg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/microL for 6 subjects, 200 to 500/microL for 6 subjects, and <200/microL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log(10)) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)

Adult↗

PubMed1996

Aphthous vaginal ulceration in two women with acquired immunodeficiency syndrome.

Two women with advanced human immunodeficiency virus infection are described who were seen with painful aphthous vaginal ulceration and CD4+ lymphocyte counts < 50 cells/mm3. A chronic rectovaginal fistula developed in one patient. In spite of extensive investigation no underlying cause of the ulceration was discovered. Clinical therapeutic response suggests that corticosteroid therapy may be of value in healing or stabilizing the destructive process. Clinicians should be aware of this complication in human immunodeficiency virus-infected women with severe vaginal pain and unexplained discharge.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Asymptomatic HIV patient with cardiomyopathy and nephropathy: case report and literature review.

We report a previously asymptomatic HIV patient with high CD4 lymphocyte count and low HIV1 viral load who developed cardiac and renal disease. Management with ACE inhibitor, diuretics and triple antiretroviral combination therapy yielded a rapid clinical response. An understanding of the spectrum of renal and cardiac derangements is essential for clinicians in managing patients with HIV disease.

AIDS-Associated Nephropathy↗

PubMed2005

Non-parametric estimation of the odds ratios for continuous exposures using generalized additive models with an unknown link function.

The generalized additive, model (GAM) is a powerful and widely used tool that allows researchers to fit, non-parametrically, the effect of continuous predictors on a transformation of the mean response variable. Such a transformation is given by a so-called link function, and in GAMs this link function is assumed to be known. Nevertheless, if an incorrect choice is made for the link, the resulting GAM is misspecified and the results obtained may be misleading. In this paper, we propose a modified version of the local scoring algorithm that allows for the non-parametric estimation of the link function, by using local linear kernel smoothers. To better understand the effect that each covariate produces on the outcome, results are expressed in terms of the non-parametric odds ratio (OR) curves. Bootstrap techniques were used to correct the bias in the OR estimation and to construct point-wise confidence intervals. A simulation study was carried out to assess the behaviour of the resulting estimates. The proposed methodology was illustrated using data from the AIDS Register of Galicia (NW Spain), with a view to assessing the effect of the CD4 lymphocyte count on the probability of being AIDS-diagnosed via Tuberculosis (TB). This application shows how the link's flexibility makes it possible to obtain OR curve estimates that are less sensitive to the presence of outliers and unusual values that are often present in the extremes of the covariate distributions.

AIDS-Related Opportunistic Infections↗

PubMed2006

Psychological resources protect health: 5-year survival and immune function among HIV-infected women from four US cities.

OBJECTIVE: Guided by Cognitive Adaptation Theory, the aim was to determine whether psychological resources (positive affect, positive expectancy regarding health outcomes, finding meaning in challenging circumstances) protect against HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV. DESIGN: The HIV Epidemiologic Research Study, a longitudinal prospective cohort study, with semi-annual interview, physical examination and laboratory assays. METHODS: A total of 773 HIV-seropositive women aged 16 to 55 years were recruited from four academic medical centers in Baltimore, Maryland; Bronx, New York; Providence, Rhode Island; and Detroit, Michigan. Semi-annually for up to 5 years, the women were interviewed, underwent physical examination, medical record abstraction, and venipuncture. Primary outcomes for these analyses included HIV-related mortality and CD4 cell count slope decline over 5 years. RESULTS: Psychological resources were inversely associated with HIV-related mortality and time to death, beyond the effects of potential confounding variables such as clinical status (e.g., HIV viral load, symptoms, antiretroviral therapy), sociodemographic characteristics (e.g. age, race), and depression at study entry (P < 0.05). Psychological resources also were inversely associated with CD4+ cell count decline (P < 0.01), serving as a possible mechanism linking resources to mortality. CONCLUSIONS: Psychological resources may protect against HIV-related mortality and immune system decline. Findings have implications for understanding individual variability in HIV disease progression. Moreover, because psychological resources are potentially amenable to change, results can be applied to clinical interventions aimed at improving the health of women with HIV.

Adult↗

PubMedDate not supplied

The use of efavirenz as a part of late rescue antiretroviral treatment.

PURPOSE: Because rescue antiretroviral strategies are increasingly needed, patients' response to a late salvage treatment including efavirenz plus a novel protease inhibitor (PI), with or without at least one novel nucleoside analogue, was assessed. METHOD: 41 consecutive patients, who underwent four or more prior therapeutic failures and received nucleoside analogues alone for > or = 18 months and a PI-based HAART for > or = 15 months, had a 12- to 24-month prospective follow-up. 6 patients who interrupted treatment after 3-8 weeks because of side effects were excluded. In the remaining 35 evaluable participants, the efavirenz-containing rescue regimen included nelfinavir in 23 cases, indinavir in 7, ritonavir in 2, and ritonavir plus hard gel saquinavir in the remaining 3 cases. 17 of 35 patients concurrently introduced one or more novel nucleoside analogues. Initial mean viremia was 4.8 +/- 0.9 log(10) HIV RNA copies/mL, while mean baseline CD4+ lymphocyte count was around 100 cells/microL. Genotyping resistance testing was obtained at the time of treatment modification. RESULTS: The virologic response was both limited and transient. A significant drop of mean viremia was reached at the third month (-0.7 log(10)), but it was not maintained beyond the sixth month; only 4 patients reached viral suppression during the first 6 months. A more evident and sustained benefit on CD4+ cell count was observed throughout the study (p <.007, compared with baseline). The 31 patients who remained evaluable beyond 12 months did not show relevant modifications of laboratory parameters. The patient subgroup that received > or = 1 novel nucleoside analogue at the time of efavirenz adjunct had a significantly more favorable virologic outcome until the ninth month of follow-up and included all cases who reached viral suppression. Antiviral resistance pattern showed frequent mutations of the protease gene, and a cross-resistance with nonnucleoside reverse transcriptase inhibitors (NNRTIs; found in 19 cases of 41), although our patients were not previously exposed to these compounds. CONCLUSION: A late salvage therapy based on efavirenz plus a novel PI is not expected to achieve a complete and sustained virologic success in patients highly experienced with both nucleoside analogues and PIs and with a concurrent elevated viremia, probably due to extensive resistances acquired through time. Our rate of virologic failure proved even greater than that observed in previous studies of salvage therapy including NNRTIs. Prior long-term treatment with isolated nucleoside analogues and HAART, the use of highly sensitive techniques for monitoring of viremia, and a quite prolonged observation period may have played a role. However, the CD4+ response proved to be more evident and sustained than the virologic one, and the concurrent introduction of >/= 1 nucleoside analogue added significantly, especially during the first 9 months of salvage therapy.

Adult↗

PubMed1997

Pregnancy outcome among HIV positive and negative intravenous drug users.

OBJECTIVE: To analyze determinants of pregnancy outcome, among HIV infected and uninfected intravenous drug users. STUDY DESIGN: A total of 315 pregnant current intravenous drug users, IVDU (151 HIV infected and 164 HIV uninfected subjects) were referred to the Center for Pregnant Drug Addicts of the Mangiagalli Clinic, Milan, Italy, for internatal care and delivery between 1985 and 1993. RESULTS: HIV uninfected and infected mothers did not differ significantly according to type of pregnancy, gestational age at childbirth, mode of delivery, pregnancy outcome and newborn weight, height, head circumference, sex and Apgar at 1 and 5 min. Out of 133 children (born to HIV infected mothers) for whom HIV status was available, 20 (15%) were HIV infected or developed AIDS-related signs and symptoms during a 24 months follow-up. The distribution of HIV infected and non infected infants was not significantly different as regards maternal CD4 lymphocyte count, week of gestation at birth, mode of delivery, infant weight, height, head circumference and Apgar at 1 and 5 min. CONCLUSION: Our data show that HIV infected women in the early stages of HIV infection are not at a higher risk of adverse course of pregnancy than HIV uninfected women. Vertical transmission rates were not associated to newborn characteristics.

Adult↗