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PubMed1999

Ocular complications of intravenous cidofovir for cytomegalovirus retinitis in patients with AIDS.

PURPOSE: To describe the frequency of anterior uveitis and ocular hypotony in cidofovir-treated patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis. METHODS: A retrospective review was performed of all patients with AIDS-related CMV retinitis during a 12-month period. The CMV retinitis activity, concurrent illnesses and medications, and CD4+ lymphocyte count were recorded in addition to the degree of anterior chamber inflammation and intraocular pressure at each visit. The frequency of uveitis and ocular hypotony in cidofovir-treated patients was determined and the possible influence of other ocular and systemic factors considered. RESULTS: Eight of 9 patients on cidofovir developed anterior uveitis. The cellular anterior chamber activity resolved with topical corticosteroid administration in all eyes with uveitis but significant flare persisted despite topical steroids in 3 patients. Posterior synechiae responded poorly to topical mydriatic therapy, resulting in inadequate mydriasis which significantly limited the fundal view. One patient developed a visually significant unilateral hypotonous maculopathy. CONCLUSIONS: Patients treated with intravenous cidofovir for AIDS-related CMV retinitis are at significant risk of ocular adverse effects. Prompt treatment with topical corticosteroids and mydriatics may control uveitis and in some cases cidofovir treatment may be cautiously continued. In the event of ocular hypotony cidofovir should be discontinued in favour of an alternative anti-cytomegaloviral agent.

AIDS-Related Opportunistic Infections↗
PubMed2004

Fatal lactic acidosis associated with highly active antiretroviral therapy in patients with advanced human immunodeficiency virus infection in Taiwan.

Lactic acidosis (LA), a rare but life-threatening adverse effect associated with antiretroviral therapy, has been reported with an increasing frequency since the mid-1990s. From June 1994 to June 2002, a total of six patients, four males and two females with a median age of 43 years (range, 30 to 74 years), had been diagnosed with LA. The estimated incidence of LA was 5.1 per 1000 patient-years (PYs) on highly active antiretroviral therapy (HAART) (95% confidence interval [95% CI], 4.5-5.5 per 1000 PYs) and 4.4 per 1000 PY on nucleoside analogues (NAs) (95% CI, 3.9-4.7 per 1000 PYs). Their median body mass index at diagnosis of LA was 17.6 kg/m(2) (range 16.3 to 22.6 kg/m(2)). The median CD4+ lymphocyte count at the initial diagnosis of HIV infection and at the onset of LA was 38 cells/ micro L (range, 4 to 103 cells/ micro L) and 108 cells/ micro L (range, 79 to 224 cells/ micro L), respectively. The most common symptoms were nausea, vomiting, and dyspnoea. All of the patients had findings suggestive of NA-related mitochondrial toxicity, such as myositis, pancreatitis, fatty hepatitis, peripheral neuropathy or lipodystrophy. The prescribed NA related to LA were stavudine in six patients, lamivudine, five, and didanosine, one. Despite treatment, all patients died of persistent circulatory collapse following LA. The median duration from diagnosis to death was eight days (range, 4-17 days). Our report highlights that clinicians caring for patients with AIDS should be alerted to the potentially fatal LA associated with antiretroviral therapy when patients present with low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea, or elevated aminotransferases.

Acid-Base Imbalance↗
PubMed1997

Epidemiology of human immunodeficiency virus infection in Central Americans treated in Harris County, Texas Hospital District facilities.

The prevalence of human immunodeficiency virus (HIV) infection among Central Americans is increasing. The purpose of this study was to describe the epidemiology of HIV infection among local Central American immigrants in the United States. Medical records of HIV-infected Central Americans treated at Harris County Hospital District (HCHD) facilities, the major source of indigent care in Houston, Texas, were retrospectively reviewed. Between January 1, 1990 and February 28, 1995, 18,156 Central Americans were seen at HCHD facilities, of whom 56 (13 females and 43 males) were identified as HIV-infected (0.3% versus 1.3% of all locally treated patients; P < 0.001, by test of binomial proportions). Most were from Honduras (n = 25) or El Salvador (n = 23). The mean age was 28.7 years, the mean CD4+ lymphocyte count at presentation was 173 cells/mm3, and 36 (64%) had acquired immunodeficiency syndrome (AIDS) at presentation. The 13 women (23% versus 22% for all locally treated HIV patients) were disproportionately Honduran (10 of 25 Hondurans versus 3 of 31 other Central Americans; P = 0.011). The HIV risk factors included heterosexuality in 46%, homosexuality in 29%. and a history of injection drug use in 7% (versus 10%, 57%, and 34%, respectively, for all locally treated HIV patients). The 76 diagnosed opportunistic infections (OIs) included a disproportionately greater number of patients with tuberculosis (n = 14, 33% versus 6% of all locally treated AIDS patients), toxoplasmosis (n = 10, 24% versus 7%), and cryptococcal meningitis (n = 9, 21% versus 7%), and a lower number of patients with pneumocystosis (n = 12, 29% versus 43%) and candida esophagitis (n = 2, 5% versus 16%). Central American immigrants infected with HIV present with relatively advanced disease, and the most frequent OIs are diseases for which effective prophylaxis exists. Targeted HIV screening and early intervention in this group are warranted.

AIDS-Related Opportunistic Infections↗
PubMed1995

Early predictors of outcome for HIV patients with neurological failure.

OBJECTIVE: To carry out a descriptive study of human immunodeficiency virus (HIV)-infected patients admitted to an intensive care unit (ICU) with neurological failure and to identify parameters that are predictive of death within 3 months. DESIGN: Case series study. POPULATION AND SETTING: A total of 84 consecutive HIV-infected patients admitted to an infectious disease ICU in a university hospital for neurological failure. A thorough clinical, laboratory, and brain computed tomography (CT) scan workup was done within 48 hours of admission. MAIN RESULTS: The mean (+/- SD) CD4+ lymphocyte count was 0.067 (+/- 0.086) x 10(9)/L. Mechanical ventilation was necessary within 48 hours of admission in 67 cases (80%). The brain CT scan revealed abscesses in 51 patients (61%). The abscesses were attributed to probable toxoplasmosis in 47 patients. A total of 57 patients died, yielding a 3-month survival rate of 32%. By the log-rank test, the following factors were predictive of death within 3 months of admission to the ICU: Glasgow Coma Scale score less than 7 (P = .01), signs of brain stem involvement (P = .001), and need for mechanical ventilation in the 48 hours after admission (P = .02). In a Cox model, only Glasgow Coma Scale score less than 7 (P = .006) and clinical signs of brain stem involvement (P = .02) were predictive of death within 3 months of admission to the ICU. CONCLUSIONS: Despite a thorough examination, no initial HIV-specific parameters were identified as predictive of death. The prognostic factors found simply reflected the severity of neurological involvement in the various etiologies.

AIDS Dementia Complex↗
PubMed1999

Combination therapy with stavudine (d4T) plus didanosine (ddI) in children with human immunodeficiency virus infection. The Pediatric AIDS Clinical Trials Group 327 Team.

OBJECTIVES: To evaluate the safety, tolerance, and antiviral activity of combination therapy with stavudine (d4T) plus didanosine (ddI) in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: The study enrolled HIV-infected children who successfully completed Pediatric AIDS Clinical Trials Group (PACTG) protocol 240 (d4T versus zidovudine [ZDV] monotherapy) without disease progression or who had received ZDV monotherapy by prescription for at least the preceding 6 months. Children who had received d4T monotherapy in PACTG 240 were assigned to treatment with d4T plus ddI (arm 1). Children who had received ZDV monotherapy in PACTG 240 or by prescription were randomized in a double-blind manner to treatment with either d4T alone (arm 2) or d4T plus ddI (arm 3). Patients were followed for 48 weeks each. RESULTS: A total of 108 children were enrolled. The mean age was 5.0 years (range, 1. 6 to 11.5 years), with mean baseline plasma HIV RNA concentration and CD4(+) lymphocyte count of 4.6 log10 copies/mL (range, 2.6 to 5. 9 log10 copies/mL) and 819 cells/microL (range, 8 to 3431 cells/microL), respectively. Both d4T monotherapy and d4T plus ddI combination therapy were well-tolerated, with 96 (89%) patients completing 48 weeks of study treatment. Plasma HIV RNA concentrations showed larger average declines in arm 3 compared with arm 2 at study week 12 (0.49 vs 0.18 log10 copies/mL, respectively); these average declines were maintained through week 48 (0.51 vs 0.17 log10 copies/mL, respectively). Fewer than 8% of the patients in any of the treatment arms had plasma HIV RNA concentrations below the limit of quantification (200 copies/mL) at any time point. CONCLUSIONS: Combination therapy with d4T plus ddI is safe and well-tolerated in HIV-infected children, producing durable, but incomplete, suppression of virus replication. This combination of nucleoside antiretroviral agents may provide a valuable backbone to protease inhibitor-containing treatment regimens for HIV-infected children.

Anti-HIV Agents↗
PubMed1996

Long-term effects of interferon-alpha in five HIV-positive patients with chronic hepatitis B.

Chronic hepatitis B viral infection is common in human immunodeficiency virus (HIV) carriers, but the effectiveness of interferon therapy is still unknown. We report the results of a long-term pilot study of five patients, who were infected with HIV and chronic hepatitis B, treated by interferon. Five males co-infected with HIV and hepatitis B virus (HBV) (mean age 27 years) were given a 6-month course of interferon (IFN)-alpha 2b 5 million units (MU) three times weekly. On initiating the treatment, their CD4 lymphocyte count was 340-553 mm-3, their CDC stage was IIa-III; all had histologically proven chronic hepatitis, with Knodell's score ranging from 6-10, and active HBV replication (HBV DNA and hepatitis B e antigen (HBeAg) were detectable). There was no associated hepatitis delta virus (H delta V) or hepatitis C virus (HCV) infection. Follow-up was for 53 months on average (24-74 months). After the treatment, hepatitis B e antibody (HBeAb) and hepatitis B s antibody (HBsAb) seroconversion was observed in one patient, HBeAb seroconversion alone in two patients, HBV DNA was absent from serum in three patients, and HBV DNA significantly decreased in one patient. The serum alanine aminotransferase (ALT) activity was normal in four patients. Histological improvement was obtained in four patients. The HIV stage remained unchanged in all patients during the whole follow-up. These preliminary results suggest that interferon can be successfully used in immunocompetent HIV carriers with chronic hepatitis B as well as in HIV-negative patients.

Acyclovir↗
PubMed2002

Iron deficiency anemia is highly prevalent among human immunodeficiency virus-infected and uninfected infants in Uganda.

Although anemia is a common finding among human immunodeficiency (HIV)-infected infants in sub-Saharan Africa, the factors contributing to the pathogenesis of anemia have not been well characterized. We sought to characterize the relative contribution of iron deficiency and chronic disease to the anemia among infants. Hemoglobin, ferritin, erythropoietin, tumor necrosis factor-alpha (TNF-alpha), neopterin, CD4(+) lymphocyte count and plasma HIV load were measured in 165 HIV-infected and 39 uninfected 9-mo-old infants seen in an outpatient pediatric clinic in Kampala, Uganda. Among HIV-infected and uninfected infants, the prevalence of anemia (hemoglobin < 110 g/L) was 90.9 and 76.9%, respectively (P = 0.015), and the prevalence of iron deficiency anemia (hemoglobin < 110 g/L and ferritin < 12 microg/L) was 44.3 and 45.4%, respectively (P = 0.92). The relatively higher prevalence of anemia among HIV-infected infants was attributed to the anemia of chronic disease. Among infants with and without iron deficiency, the fitted regression line was log(10) plasma erythropoietin = 2.86 - 0.016.hemoglobin, and log(10) plasma erythropoietin = 4.11 - 0.028.hemoglobin, respectively, with a difference in the slope of the regression lines between log(10) erythropoietin and hemoglobin among infants with and without iron deficiency (P = 0.049). Infants in Uganda have an extremely high prevalence of anemia, and nearly half of the anemia is due to iron deficiency. The erythropoietin response to anemia appears to be upregulated among infants with iron deficiency.

Anemia, Iron-Deficiency↗
PubMed2003

A phase I study of a six-week cycle of immunotherapy with Murabutide in HIV-1 patients naive to antiretrovirals.

BACKGROUND: Limitations in the use of antiretroviral therapy suggest the need for additional approaches to enhance immune restoration and the control of HIV-1 replication. Therefore, we evaluated the clinical tolerance and biological effects of immunotherapy with the synthetic immunomodulator Murabutide in 9 treatment-naive HIV-1 patients presenting with CD4+ lymphocyte counts >500 cells/mm3 and plasma viral loads <30.000 copies/ml. MATERIAL/METHODS: Murabutide was administered at a daily dose of 7 mg on 5 consecutive days per week, for a period of 6 weeks. The study duration extended over 22 weeks, and clinical, virological, and immunological evaluations were carried out on 2 occasions before, during, and after immunotherapy. RESULTS: With acceptable clinical tolerance and only 2 reversible grade III adverse events, clinical and virological parameters remained highly stable throughout the study period. However, maintained or improved lymphoproliferative responses to several recall and HIV-1 antigens, as well as modest but significant increases in the percentages of naive cells were noted during or/and after immunotherapy. These changes could not be demonstrated in an observation group of 9 additional patients who were identically followed for a 22-week period. CONCLUSIONS: Our results suggest that non-specific immunotherapy targeting dysfunctions in innate immunity could bring about restoration of immune responses in HIV disease.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2003

Evaluation of antiretroviral treatment in two private medical centers in Addis, Ethiopia.

Ethiopia is one of the countries affected severely by the HIV/AIDS epidemic in sub-Saharan Africa. The disease is gradually fatal without antiretroviral therapy (ARV). The experience with antiretroviral therapy is limited in this country. This study is the first of its kind that has evaluated the status and implication of the clinical use of ARV drugs in Ethiopia. The guidelines for the initiation of treatment, the strengths and weaknesses of such treatment and the implications of similar intervention in a wider scale were assessed. Clinical records of 33 patients under follow-up and treatment with ARV in Hayat Hospital and Bethezatha Medical Center were identified. Data were collected from the medical records using a tool designed for the purpose. All 33 patients were receiving ARV for a mean duration of about 4 months. Twenty- three (69.7%) were males and 10 (30.3%) were females and the mean age was 38 years. Fifteen (45.5%) were married, fourteen (40.7%) were single, one (3%) divorced and there was no record for three (9.1%). Fifteen (45.5%) were businessmen, seven (21.2%) were private employees, four (12.1%) civil servants and in the remaining seven (21.2%) their occupation was not recorded. The decision to initiate ARV therapy was entirely based on the presence of symptomatic HIV disease. CD4+ lymphocyte count was done in 24 (72.7%) and basic hematological tests were done for all. However, biochemical investigations were incomplete in all of them. Triple therapy was started for all patients and the cost of the drugs was covered by their family in eleven (33.3%), by the patients in twenty-two (66.7%). Side effects of the drugs were noted in ten (30.3%) that resulted in change of the regimen in two and drug interruption in one. Response to treatment was entirely based on clinical parameters only. Twenty-three patients (69.7%) were noted to improve while nine (27.3%) remained the same and death occurred in one (3%). Standard triple therapy was used in all patients in this study and symptomatic HIV disease was the reason for the initiation of treatment. The improvement observed was not substantiated by immunological or virological parameters. Thus, the impacts of ARVs cannot be measured and the response documented in this study can be due to the effective treatment of opportunistic infections. Hence a standard protocol should be developed based on the minimum set-up required for the initiation of ARV therapy.

Adult↗
PubMed2005

An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children.

OBJECTIVE: The multidrug-resistance transporter gene (MDR1) encoding for P-glycoprotein (P-gp) and genes encoding for isoenzymes of cytochrome P450 (CYP) have an important role in transport and metabolism of antiretroviral agents. This research examined the impact of single nucleotide polymorphisms (SNP) of MDR1 and CYP genes on nelfinavir and efavirenz pharmacokinetics and the response to highly active antiretroviral therapy (HAART) in HIV-1 infected children. METHODS: Seventy-one HIV-1-infected children from PACTG 382 receiving nelfinavir, efavirenz and one or two nucleoside reverse transcriptase inhibitors had genomic DNA from PBMC evaluated for MDR1 and CYP SNP by real-time PCR. Plasma drug concentrations, CD4 lymphocyte counts and HIV-1 RNA were measured during HAART. RESULTS: The frequencies of C/C, C/T and T/T genotypes in the MDR1-3435-C-->T polymorphisms were 44% (n = 31), 46% (n = 33) and 10% (n = 7), respectively. Ninety-one percent of children with the C/T genotype reached plasma HIV-1 RNA < 400 copies/ml by week 8 compared to 59% of children with the C/C genotype (P = 0.01). Children with the C/T genotypes had higher 8 h postdose concentration (P = 0.02) and lower clearance rate (P = 0.04) for nelfinavir compared to those with the C/C genotype. The seven children with the T/T genotype had nelfinavir pharmacokinetics and virologic response similar to those with the C/C genotype. No compensatory polymorphisms were observed between MDR1 and CYP genotypes. CONCLUSIONS: HIV-1 infected children with the MDR1-3435-C/T genotype had more rapid virologic responses to HAART at week 8 with higher plasma nelfinavir concentrations compared to those with the C/C genotype. These findings suggest that P-gp may play an important role in the pharmacokinetics and virologic response to HAART containing nelfinavir.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome.

OBJECTIVE: To examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DESIGN: Cross-sectional study. SETTING: HIV primary care practices. PATIENTS: PI-treated patients with lipodystrophy (n= 14) and PI-treated (n= 13) and PI-naive (n= 5) patients without lipodystrophy. MAIN OUTCOME MEASURES: Body composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. RESULTS: PI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) x 10(-4) (min(-1)/microU/ml) versus 3.2 x 10(-4) and 4.6 x 10(-4) (min(-1)/microU/ml), respectively; P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass; P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. CONCLUSIONS: Body fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

Adipose Tissue↗
PubMed2004

[Liver transplantation in patients with HIV infection: a reality in 2004].

According to current estimates, there are 60,000 to 80,000 HIV and HCV coinfected individuals in Spain, and 5,000 to 10,000 HIV and HBV coinfected individuals. Among these patients, 10% to 15% have liver cirrhosis. Thus, end-stage liver disease is one of the major causes of death in our country. Liver transplantation is the only therapeutic option for these patients. Accumulated experience in North America and Europe in the last five years indicates that three-year survival in HIV-positive liver transplant recipients is similar to that of HIV-negative recipients. The selection criteria for HIV transplant candidates includes the following: no history of opportunistic infections, CD4 lymphocyte count higher than 100 cells/mm3, and HIV viral load suppressible with antiretroviral treatment. In Spain, where the majority of patients are former drug abusers, complete abstinence from heroin or cocaine use during two years is also required, with the possibility of the patient being in a methadone program. To date 26 hepatic transplants have been performed in the same number of patients, with only two deaths (7%) after a median follow-up of eight months (1-28). The main problems in the post-transplantation period in all the series has been recurrent HCV infection, which is the principle cause of post-transplantation mortality, and pharmacokinetic and pharmacodynamic interactions between the antiretroviral and immunosuppressive agents. There is little experience with pegylated interferon and ribavirin treatment in this population.

Anti-HIV Agents↗
PubMed2000

Peripheral CD4+/CD8+ T-lymphocyte counts estimated by an immunocapture method in the normal healthy south Indian adults and HIV seropositive individuals.

BACKGROUND: Flow cytometry is the standard method for the estimation of CD4/CD8 counts, but the high initial investment for this instrument and costly reagents make it unaffordable to most of the centers in a developing country like India. OBJECTIVES: To evaluate the feasibility of an alternate system for the estimation of CD4 and CD8 counts in normal south Indian adults and validate the usefulness of this assay to monitor the counts in HIV seropositive individuals. STUDY DESIGN: Forty-six normal healthy adults and 68 HIV seropositive individuals both belonging to south Indian linguistic groups were enrolled in this cross-sectional study. The HIV seropositive individuals included 54 HIV-1, 9 HIV-2 and 5 HIV 1&2 infected individuals serologically confirmed by one of the commercial Immunoblot kits. The Capcellia CD4/CD8 whole blood assay, an immuno-capture ELISA based kit from Sanofi DIAGNOSTICS Pasteur, (France) was used with a few modifications in the procedure to measure the CD4 and CD8 counts. RESULTS: The mean CD4 cell counts were 1048 (central 95 centile only), 746 and 424 for the normal healthy adults, asymptomatic HIV seropositives and symptomatic HIV patients, respectively, and the mean CD8 counts were 595, 889 and 732, respectively. Statistically significant differences were observed in the CD4 cell counts between HIV seronegative healthy adults and asymptomatic (P < 0.001) as well as asymptomatic and symptomatic (P < 0.05) HIV infected individuals. The mean CD4 counts of asymptomatic HIV-2 infected individuals was significantly higher than the counts of asymptomatic HIV-1 infected individuals (P < 0.05). CONCLUSIONS: This is an user friendly test and can be an alternate to flow cytometry for the estimation of peripheral T-lymphocyte subsets in developing countries. The assay system has certain limitations inherent to ELISA techniques.

Adult↗
PubMed1999

Clinical analysis of Mycobacterium tuberculosis infection in patients with acquired immunodeficiency syndrome.

From January 1990 to July 1998, twelve patients (10%) among 120 patients with human immunodeficiency virus infection who were hospitalized in the Veterans General Hospital-Taipei, were proved to have Mycobacterium tuberculosis infection. The mean age of these patients was 38 years, range: 25-62 years. All patients studied were in the advanced stage of acquired immunodeficiency syndrome (AIDS) with a mean circulatory CD4 lymphocyte count of 21/microL (range: 0-64/microL) and a much higher HIV viral load at initial diagnosis of M. tuberculosis infection. Because of no significant difference in the HIV viral load between patients with active pulmonary tuberculosis and those with extrapulmonary tuberculosis in this study, dissemination of M. tuberculosis did not correlate directly with a high HIV viral load, but was possibly related to the virulence of the organism itself. Chest radiographic findings at initial diagnosis of pulmonary tuberculosis were variable and atypical. Most patients (62.5%) presented with a primary pattern (lower lobe or diffuse infiltrates), while hilar lymphadenopathy was noted in more than half of the patients and cavitation was less common (only one patient). Ten patients (83.3%) had extrapulmonary involvement; the most common site being the lymph nodes. Most patients with classic drug-sensitive tuberculosis responded well to conventional standard regimens of anti-tuberculosis therapy. Since tuberculosis is transmittable, treatable, and possibly preventable, moreover the clinical presentation of tuberculosis in the patients with AIDS may be atypical and unusual, clinical physicians must keep an alert dealing with these patients for early identification and early treatment.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Resistance analyses in HIV infected patients with a history of multiple antiretroviral treatment regimens.

OBJECTIVE: To assess HIV-1 isolate based resistance profiles from extensively pretreated patients and effects of a resistance guided switch of antiretroviral therapy. METHODS: In a prospective study phenotypic and genotypic resistance analyses were performed on HIV infected individuals with failure of the current therapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyte counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks. RESULTS: All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations and phenotypic resistance to AZT and 3TC were found in over 80% of individuals; resistance to DDI and D4T was detected in less than 10% of cases. A resistance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or more drugs compared with patients with resistance to less than two drugs of ongoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patients with resistance to at least two drugs in the previous regimen. CONCLUSIONS: Among different RTI, the profile of clinically relevant resistance indicates pronounced differences when looking at separate drugs. Regarding virological response, in the context of available drugs, resistance tested with currently used methods is of limited value in extensively pretreated patients and seems to have its value primarily in first or second switch of therapy.

Adult↗
PubMed1999

Corynebacterium pseudodiphtheriticum: an easily missed respiratory pathogen in HIV-infected patients.

Despite being a well-known respiratory pathogen for immunocompromised patients, Corynebacterium pseudodiphtheriticum has uncommonly been reported to occur in persons with infection attributable to HIV virus. We report three cases of respiratory tract infection attributable to C. pseudodiphtheriticum in HIV-infected patients and review the four previous cases from the medical literature. All of them were male with a median CD4 lymphocyte count of 110 cells/mm3 (range, 18-198/mm3); five of the seven cases occurred in persons for whom AIDS was diagnosed previously. The onset of symptomatology was usually acute and the most common radiographic appearance was alveolar infiltrate (six patients) with cavitation (two patients) and pleural effusion (two patients). In five of the seven cases, C. pseudodiphtheriticum was isolated from bronchoscopic samples and in the remaining two cases was recovered from lung biopsy (one patient) and sputum (one patient). In the three patients reported herein and in one previous case from the medical literature, quantitative culturing of bronchoscopic samples obtained through either bronchoalveolar lavage or protected brush catheter procedures yielded more than 10(3) CFU/mL. All the strains tested were susceptible to penicillin and vancomycin. Resistance to macrolides was common. Recovery was observed in six of the seven patients. C. pseudodiphtheriticum should be regarded as a potential respiratory pathogen in HIV-infected patients. This infection presents late in the course of HIV disease and it seems to respond well to appropriate antibiotic treatment in most of the cases. This easily overlooked pathogen should be added to the list of organisms implicated in respiratory tract infections in this population.

AIDS-Related Opportunistic Infections↗
PubMed1997

Impact of pregnancy on maternal AIDS.

OBJECTIVE: To assess the impact of pregnancy on maternal acquired immunodeficiency syndrome (AIDS) among tribal women in India. STUDY DESIGN: From February 1992 to February 1996, 71 tribal women from Manipur, India, with AIDS (Centers for Disease Control stage iii/iv), matched for age, parity, CD4 lymphocyte count and demographic characteristics, were recruited into a prospective study. Thirty-two (49%) of these women were pregnant (8-10 weeks) (group A) and 38 (51%) nonpregnant (group B). RESULTS: Pneumocystis carinii pneumonia followed by miliary tuberculosis and wasting disease were the most common AIDS-defining illness and cause of maternal death in both groups. A total of 28 (39%) women died as a direct result of their AIDS-defining illness; 10 (27%) of them were among the nonpregnant women as compared to 18 (56%) deaths among the pregnant women (P = .17, odds ratio 3.7285, 95% confidence interval 1.23, 11.58). Three (16%) of these 18 deaths occurred within 14 weeks of an uneventful first-trimester medical termination of pregnancy. Thirteen women (41%) died undelivered at 30-34 weeks' gestation, and two died within 3 weeks of delivery. Fourteen (44%) women vaginally delivered 14 preterm infants, between 28 and 35 weeks' gestation. Eleven of these infants died within six weeks; nine deaths were a direct result of prematurity and clinical diagnosis of an AIDS-defining illness. The mean survival time was 9.72 months for the pregnant women and 22.6 months for the nonpregnant women (P = .066). CONCLUSION: Pregnancy increased maternal and fetal mortality in these AIDS-infected women.

AIDS-Related Opportunistic Infections↗
PubMed1999

Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team.

BACKGROUND: Maternal, obstetrical, and infant-related factors associated with the risk of perinatal transmission of human immunodeficiency virus type 1 (HIV-1) were identified before the widespread use of zidovudine therapy in pregnant women. The risk factors for transmission when women and infants receive zidovudine are not well characterized. METHODS: We examined the effects of maternal, obstetrical, and infant-related characteristics and maternal virologic and immunologic variables on the risk of perinatal transmission of HIV-1 among 480 women and their infants, all of whom received zidovudine. The women and infants were participating in a phase 3 trial of passive immunoprophylaxis for the prevention of perinatal transmission. RESULTS: In univariate analyses, the risk of perinatal transmission was associated with each of the following: decreased maternal CD4+ lymphocyte counts at base line; decreased maternal HIV p24 antibody levels at base line and delivery; increased maternal HIV-1 titer at base line and delivery; increased maternal HIV-1 RNA levels at base line and delivery; and the presence of chorioamnionitis at delivery. In multivariate analyses, the only independent risk factor was the maternal HIV-1 RNA level at base line (odds ratio for transmission, 2.4 per log increase in the number of copies; 95 percent confidence interval, 1.2 to 4.7; P=0.02) and at delivery (odds ratio, 3.4; 95 percent confidence interval, 1.7 to 6.8; P=0.001). There was no perinatal transmission of HIV-1 among the 84 women who had HIV-1 levels below the limit of detection (500 copies per milliliter) at base line or the 107 women who had undetectable levels at delivery. CONCLUSIONS: Among pregnant women and their infants, all treated with zidovudine, the maternal plasma HIV-1 RNA level was the best predictor of the risk of perinatal transmission of HIV-1. Antiretroviral therapy that reduces the HIV-1 RNA level to below 500 copies per milliliter appears to minimize the risk of perinatal transmission as well as improve the health of the women.

Analysis of Variance↗