Symptomatic HIV-infected Patients Research Articles

Predominant amino acid substitutions in NS5B gene of hepatitis C virus in blood donors and treatment-naïve hepatitis and HIV patients in Nigeria

Background: Hepatitis C virus (HCV) genome undergoes high rate of mutation, which results in generation of genetically diverse HCV isolates. There is paucity of data on mutations in the nonstructural 5b (NS5b) gene of circulating HCV and their implications in the Nigerian population. Here, we identified clinically-important mutations in HCV isolates, which may influence response to therapy and disease prognosis.
 Methodology: HCV RNA was extracted from a total of 301 blood samples collected from 99 symptomatic treatment-naïve hepatitis patients, 125 HIV-infected individuals and 77 asymptomatic blood donors in Ibadan, Nigeria. The RNA was reverse–transcribed to complimentary DNA and HCV NS5B gene amplified by nested PCR. The amplified products of 42 HCV were sequenced and sequences were aligned with those from GenBank and HCV databases in MEGA 7.0. Nucleotide sequences were translated to amino acids while substitutions in the amino acids were analyzed with reference to H77 prototype strain of HCV.
 Results: A total of 10 amino acid polymorphisms were observed from the 42 sequenced NS5B gene, with the major clinically-important amino acid mutations being S15G in 28 (66.7%) participants, T7N (24, 57.1%), G61R (23, 54.8%), S54L (22, 52.4%), G89E (14, 33.3%), T79M (12, 28.6%), and T711 (11, 26.2%). Others were Q67R (7, 16.7%), Q47H (7, 16.7%) and S84F (2, 4.8%). S15G/A/V mutations were more predominant in patients with HIV (76.9%, 10/13) followed by patients with clinical hepatitis (75.0%, 12/16) and blood donors (46.1%, 6/13). Q67R and T71I mutations were not predominant in patients with clinical hepatitis as they were detected in only 31.3% (5/16) and 43.8% (7/16) participants respectively, compared to S15G (75.0%, 12/16), S54L (68.8%, 11/16), G61R/E (68.8%, 11/16) and T7N/S (56.3%, 9/16). There was no statistically significant difference in the distribution of each of the 10 amino acid polymorphisms detected within patients with symptomatic clinical hepatitis (x2=9.311, p=0.409), HIV-infected patients (x2=13.431, p=0.1440) and asymp- tomatic blood donors (x2=3.775, p=0.9256). Similarly, there was no significant difference in the distribution between the 3 categories of the study participants except for T79M mutation, which was significantly higher in HIV-infected patients (61.5%, 8/13) compared to patients with clinical hepatitis (18.8%, 3/16) and asymp- tomatic blood donors (7.7%, 1/13) (x2=10.456, p=0.0054).
 Conclusion: Mutations in the NS5B gene could be associated with worse prognosis of the disease or antiviral failure due to viral resistance in patients undergoing therapy. The absence of Q47H mutations in majority of the study participants in our study implies that they will not respond well to daprevir and mericitabine. Screening of patients for pre-existing resistant mutations before commencement of therapy and monitoring during and after therapy are recommended.

Prevalence of renal dysfunction among HIV infected patients receiving Tenofovir at Mulago: a cross-sectional study

BackgroundThere is an increasing burden of non-communicable disease globally. Tenofovir disoproxil fumarate (TDF) is the most commonly prescribed antiretroviral drug globally. Studies show that patients receiving TDF are more prone to renal dysfunction at some point in time during treatment. Evaluation of kidney function is not routinely done in most HIV public clinics. Identification of renal dysfunction is key in resource constrained settings because managing patients with end stage renal disease is costly.MethodThis was a cross-sectional study conducted at an outpatient clinic in 2018 involving patients on TDF for at least 6 months who were 18 years or older. Patients with documented kidney disease and pregnancy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula. Renal dysfunction was defined as any of the following; either eGFR< 60 mL/min/1.73m2,or proteinuria of ≥2+ on urine dipstick, glycosuria with normal blood glucose. Electrolyte abnormalities were also documented.ResultsWe enrolled 278 participants. One hundred sixty nine (60.8%) were females, majority 234(84.2%) were < 50 years old, 205 (73.74%) were in WHO stage 1, most participants 271(97.5%) in addition to TDF were receiving lamivudine/efavirenz. The median age was 37(IQR 29–45) years; median duration on ART was 36 (IQR 24–60) months. The prevalence of renal dysfunction was 2.52% (7/278). Most noted electrolyte abnormality was hypocalcaemia (15.44%).ConclusionsThe prevalence of renal dysfunction was low though some participants had hypocalcaemia. Screening for kidney disease should be done in symptomatic HIV infected patients on TDF.

Increase in sexually transmitted infections in a cohort of outpatient HIV-positive men who have sex with men in the Parisian region

ObjectiveTo describe the increased incidence of sexually transmitted infections (STIs) in a cohort of HIV-infected men who have sex with men (MSM), followed in a tertiary hospital of the Île-de-France region. Materials and methodsWe performed a monocentric, retrospective, and prospective study. We included symptomatic HIV-infected MSM patients who consulted for their annual consultation. ResultsOne hundred and eighty patients were seen between 2008–2011 and 215 between 2012–2015. We observed an increased incidence of STIs between the two periods (14 and 29.3%, respectively). These STIs includes: syphilis, hepatitis C, urethritis, and proctitis due to Chlamydia trachomatis and Neisseria gonorrhea. ConclusionA better management of symptomatic and asymptomatic STIs is needed for HIV-infected MSM patients.

Assessment of HIV disease progression before and after initiation of anti­retroviral therapy by CD4 &amp; CD8 T-lymphocyte count and viral load assay

&lt;p&gt;&lt;strong&gt;Backgrounds:&lt;/strong&gt; As there is no published data regarding the response to Anti-retroviral therapy (ART) among HIV patients from Bangladesh. The present study was designed to determine the immunological and virological responses of HIV infected Bangladeshi adults starting ART. Objectives: To monitor the changes of CD4 and CD8 T-lymphocyte count and Viral load (VL) before and after three and six months of starting ART.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; 20 symptomatic HIV infected patients with CD4 T-lymphocyte count of &amp;lt;350 cells/µ] of blood were initiated ART.CD4 and CDS T-lymphocyte counts were estimated by Flowcytometer and VL was dete1mined by real-time PCR technique.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; The mean CD4 T-lymphocyte count among the sn1dy patients were 177±127 cells/µl before initiation of ART. After ART initiation, their mean CD4 count increased significantly to 368±181 and 452±183 cellshll after three and six months respectively (P&amp;lt;0.0001).The mean CDS T-lymphocyte counts were 901±650 cells/µ! before initiation of ART, which increased to I 085±393 and 1121±372 cells/µl after three and six months respectively after ART initiation (P&amp;gt;0.05). Before ART initiation, the mean VL was 5.25±1.19 log10 (copies/ml) among the study population which became undetectable in 15 (75%) patients after three months of ART and in another 2 (10%) patients after 6 months of ART initiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Our study concluded that, ART is effective in slowing the progression of HIV infection to AIDS with good immunological and virological outcome among the ART initiators.&lt;/p&gt;

Prevalence of Disseminated Cryptococcosis among Human Immunodeficiency Virus Infected Patients in Benin City, Nigeria

Aim: To determine the prevalence of disseminated cryptococcosis among symptomatic HIVinfected patients, attending the Antiretroviral Treatment Clinic at the University of Benin Teaching Hospital, Benin City, Nigeria. Study Design: Cross-sectional study. Place and Duration of Study: Department of Internal Medicine and Department of Medical Microbiology, University of Benin Teaching Hospital, Edo State, Nigeria, between September 2010 Original Research Article Joseph et al.; BJMMR, 6(7): 715-722, 2015; Article no.BJMMR.2015.248 716 and August 2011. Methodology: Five hundred consecutive symptomatic HIV-infected patients, on ART were enrolled into this cross-sectional study (266 males, 234 females, age range 18-81 years, mean age, 40.08 years). A blood sample collected from each participant was screened for serum cryptococcal antigen (CRAG) using the cryptococcal Latex agglutination test. The viral load and CD4+ T -cell count were also determined in parallel. A structured questionnaire was used to gather Information on socio demographic characteristics, medical and treatment history of participants. Data collected and the results of laboratory tests were analyzed using the SPSS software, version 22.0. Results: The prevalence of serum cryptococcal antigen was 9.8%. Majority (66.8%) of the participants had a CD4+ T-cell count of less than 100 cells/μl. The association between serum CRAG and CD4+ T-cell was found to be significant (P < .001). Viral load done for only 90 of the participants was high in 51.1%. The association between serum CRAG and viral load was found to be significant (P < .001). Conclusion: The prevalence of serum CRAG was high among symptomatic HIVinfected patients on ART, in Benin city, Nigeria, despite ART implementation. There is need therefore for a routine cryptococcal antigen test for all symptomatic HIV-infected patients on ART, while further microbiological investigations for those with positive result are recommended for appropriate medical intervention.

Evaluation of a Diagnostic Algorithm for Sputum Smear–Negative Pulmonary Tuberculosis in HIV-Infected Adults

The Revised National TB Control Program bases diagnosis of tuberculosis (TB) on sputum smear examination and response to a course of antibiotics, whereas World Health Organization recommends early chest radiography [chest x-ray (CXR)] for HIV-infected symptomatic patients. We evaluated the utility of initial CXR in the diagnostic algorithm for symptomatic HIV-infected patients with negative sputum smears. HIV-infected ambulatory patients with cough or fever of ≥2 weeks and 3 sputum smears negative for acid-fast bacilli were enrolled in Chennai and Pune, India, between 2007 and 2009. After a CXR and 2 sputum cultures, a course of broad-spectrum antibiotics was given and patients were reviewed after 14 days. Sensitivity, specificity, positive and negative predictive values of symptoms, CXR, and various combinations for diagnosing pulmonary tuberculosis (PTB) were determined, using sputum culture as gold standard. Five hundred four patients (330 males; mean age: 35 years; median CD4: 175 cells per cubic millimeter) were enrolled. CXR had a sensitivity and specificity of 72% and 57%, respectively, with positive predictive value (PPV) of 21% and negative predictive value (NPV) of 93% to diagnose PTB. TB culture was positive in 49 of 235 patients (21%) with an abnormal initial CXR and 19 of 269 patients (7%) with a normal CXR (P < 0.001). Sensitivity and specificity of cough ≥2 weeks for predicting PTB was 97% and 6%, with PPV and NPV of 14% and 94%, respectively. Although moderately sensitive, basing a diagnosis of TB on initial CXR leads to overdiagnosis. An absence of weight loss had a high NPV, whereas none of the combinations had a good PPV. A rapid and accurate diagnostic test is required for HIV-infected chest symptomatic.

Cardiac dysfunction in pauci symptomatic human immunodeficiency virus patients: a meta-analysis in the highly active antiretroviral therapy era

Human immunodeficiency virus infection (HIV) has been associated with cardiac dysfunction that, if present, can negatively affect morbidity and mortality of HIV-infected patients. Unfortunately, many of the studies on this topic were performed before the highly active antiretroviral therapy (HAART) was established. Thus, we performed a comprehensive meta-analysis to critically appraise the incidence of cardiac dysfunction in HIV-infected pauci symptomatic patients. Medline, Cochrane Library, and Biomed Central were systematically screened for studies reporting on systolic and/or diastolic dysfunctions in HIV pauci-symptomatic patients. Baseline treatment and cardiac imaging data were appraised and pooled with random effect methods computing summary. At pooled analysis, including a total of 2242 patients from 11 studies, an overall average incidence of traditional cardiovascular risk factors was observed, while a low rate of previous coronary artery disease was reported. Incidence of systolic and diastolic left ventricular dysfunction was 8.33% (95% CI: 2.20-14.25) and 43.38% (95% CI: 31.73-55.03), respectively. Diastolic dysfunction was graded as first [31.85% (95% CI: 24.85-43.73)], second [8.53% (95% CI: 2.12-14.93)], and third degree [3.02% (95% CI: 1.78-4.27)]. At multivariate analysis, a high sensitivity C-reactive protein level >5 mg/L, active tobacco smoking and previous history of myocardial infarction were predictors of left ventricular systolic dysfunction [odd ratio 1.70 (95% CI: 1.03-2.77); 1.57 (95% CI: 1.03-2.34); and 15.90 (95% CI: 1.94-329.00), respectively]. Hypertension (OR = 2.30; 95% CI: 1.20-4.50) and older age (OR = 2.50 per 10 years increase; 95% CI: 1.70-3.60) were predictors of left ventricular diastolic dysfunction (Figure 3). Systolic and diastolic dysfunction represent a common finding in pauci symptomatic HIV-infected patients, regardless to HAART.

Heterogeneous effects of exogenous IL-2 on HIV-specific cell-mediated immunity (CMI).

A characteristic feature associated with HIV-1 infection of the human host is a chronic decline in circulating CD4+ T helper/inducer cell numbers. Impaired cell-mediated immune functions usually occur in parallel with the decline in CD4+ T cells. Activated CD4+ T helper cells are a major source of endogenous IL-2 which is required for the immunoregulation of both antigen-specific B cells and CD8+ T cells. HIV-specific T cell proliferative responses are said to be weak and inconsistent, even during the asymptomatic phase of disease. We thus wished to determine how exogenous IL-2 affected HIV-specific T cell proliferation at different stages of the disease. Our cohort of 81 included both asymptomatic and symptomatic HIV-infected patients as well as uninfected normal donors. Proliferative responses of peripheral blood mononuclear cells (PBMC) that were elicited during culture with an immunodominant gp41-derived synthetic peptide, gp41[8], and which were known to be CD8+ cell-associated in asymptomatics only, were used to analyse the effects of exogenous IL-2. IL-2 had three main effects on HIV-specific proliferation, namely (i) an additive effect, (ii) a synergistic effect, and (iii) an induced effect. More specifically, low dose exogenous IL-2 frequently augmented lymphoproliferation in both asymptomatic and symptomatic gp41[8] responders. In most symptomatics, however, who were predominantly gp41[8] non-responders, exogenous IL-2 induced lymphoproliferation. Flow cytometric analyses using dual immunofluorescence were used to analyse the T cell subset distribution of proliferating PBMC cultures. During culture with gp41[8], both CD4+ and CD8+ T cell numbers increased. However, after the addition of exogenous IL-2 to gp41[8]-containing cultures, CD8+ cell-associated lymphoproliferative responses were preferentially augmented. These results suggest that in symptomatics there is an inadequate supply of endogenous IL-2 to help maintain the strong and effective CD8+ cell-associated anti-viral immunity, and an exogenous supply of IL-2 may be required.

Pessoas vivendo com HIV/AIDS: enfrentamento, suporte social e qualidade de vida

A pesquisa testou modelo sobre as relações entre qualidade de vida (QV), condição clínica, escolaridade, situação conjugal, enfrentamento e suporte social, em pessoas portadoras do HIV/AIDS. Participaram 241 pessoas (161 homens), de 20 a 64 anos, 169 sintomáticas e 72 assintomáticas, 208 delas em uso de terapia anti-retroviral. A variável critério QV foi investigada nas dimensões psicossocial, física, do ambiente e qualidade de vida geral, mediante análises de regressão múltipla hierárquica. Suporte social emocional, enfrentamento focalizado na emoção, enfrentamento focalizado no problema e viver com parceiro(a) foram preditores significativos da dimensão psicossocial da QV, alcançando a maior variância explicada (59% ajustado). Suporte social emocional e enfrentamento focalizado na emoção foram preditores significativos nas análises relativas às demais dimensões da QV. Discutem-se implicações para as práticas de saúde referentes às ações profissionais propiciadoras do bem-estar psicológico e da qualidade de vida em pessoas vivendo com HIV/AIDS.

Pneumocystis carinii pneumonia in HIV/AIDS patients at an urban district hospital in Kenya.

Pneumocystis carinii pneumonia has generally been regarded to be an uncommon opportunistic infection in HIV infected individuals in sub-Saharan Africa. The reason for this has not been clear but postulates included a lack of suitable pathogenic types in the African environment, diagnostic difficulties and the more commonly held belief that African HIV infected individuals were dying early from common non-opportunistic pathogens before severe degrees of immunosuppression occured. Recently a trend has emerged at the Mbagathi district hospital whereby an increasing number of HIV infected patients are empirically treated for Pneumocystis carinii pneumonia (PCP) based on clinical and radiological features. To determine the prevalence of PCP and clinical outcomes of HIV infected patients presenting at the Mbagathi District Hospital, Nairobi with the presumptive diagnosis of PCP. Mbagathi District Hospital, a 169-bed public hospital in Nairobi, Kenya. Patients presenting with a sub-acute onset of cough and dyspnoea were eligible for the study if they were found to have bilateral pulmonary shadows and had negative sputum smears for AFBS. Consenting patients who had no contraindication to fiberoptic bronchoscopy had a clinical evaluation which was followed with a fiberoptic bronchoscopy procedure where bronchoalveolar lavage fluid (BALF) was obtained. BALF was examined for cysts of P. carinii using toluidine blue stain and immunofluorescent antibody test (IFAT). BALF was also processed for fungi, bacteria and mycobacteria using routine procedures. Standard treatment with high dose cotrimoxazole was offered to all patients who were then followed up until discharge from hospital or death whichever came first. Between June 1999 and August 2000 a total of 63 patients were referred for bronchoscopy. Of these four declined to undergo the fiberoptic bronchoscopy procedure, four died before the procedure could be done, one was judged too sick to undergo the procedure and three had been on cotrimoxazole for longer than five days. Thus 51 patients underwent bronchoscopy. Pneumocystis carinii stain was positive in 19 (37.2%) while death occured in 16 (31.4%) of the 51 patients. There were more deaths in those without PCP but this difference was not statistically significant (odds ratio 0.68 (95% CI 0.35-1.32; P=0.2). PCP was found to be common in HIV infected patients presenting with clinical and radiological features of the disease. The mortality rate for patients with a presumptive diagnosis of PCP is high. This study suggests that cotrimoxazole preventive therapy may be a useful intervention in symptomatic HIV infected patients in Kenya for the prevention of PCP and may avert deaths from this disease.

Special histologic stains are rarely beneficial for the evaluation of HIV-related gastrointestinal infections.

During a 28-month period, endoscopic mucosal biopsy specimens from all HIV-infected patients were submitted for routine histologic evaluation. Immunoperoxidase staining for cytomegalovirus and herpesvirus antigens (esophagus), mycobacterial and fungal staining, and Gram staining of mucosal biopsy specimens were done. Special fungal and acid-fast stains were selectively performed in patients with absolute CD4 cell counts of less than 200 cells per microliter (200 x 10(6)/L) and/or with diarrhea and or wasting syndrome. Treatment was based on the endoscopic and histologic findings, and long-term follow-up was performed. The 121 symptomatic HIV-infected patients underwent 221 upper and/or lower endoscopies with 285 biopsy sites. The sensitivity and specificity of H&E staining for the diagnosis of gastrointestinal cytomegalovirus were 97% and 100%, respectively. The results of fungal and mycobacterial stains neither altered therapy nor identified previously undiagnosed infections in any patient. Long-term follow-up revealed no patient in whom an infection was missed on routine H&E, which affected outcome. Routine H&E staining is accurate for the diagnosis of gastrointestinal opportunistic infections in HIV-infected patients. Special histologic stains for fungal, mycobacterial, and viral infections did not increase the diagnostic yield or alter medical therapy but doubled the costs.

Human immunodeficiency virus type-1 Nef protein induces blood–brain barrier disruption in the rat: role of matrix metalloproteinase-9

We recently showed that MMP-9 activity was detectable in the cerebrospinal fluid (CSF) of about half of neurologically symptomatic HIV-infected patients. Using an experimental animal model, we detected MMP-9 activity in CSF samples from rats that had been injected intracisternally with recombinant HIV-1 Nef protein, but not after injection of heat-treated Nef, gp120, gp160 or PBS. Nef also induced a breaching of the blood–brain barrier (BBB), which could be inhibited by pretreatment with the matrix metalloproteinase (MMP) inhibitor batimastat. In vitro Nef only slightly induced MMP-9 activity in freshly isolated human peripheral blood mononuclear cells and in the murine macrophage cell line RAW 264.7, but not in endothelial, neuronal or astroglial cell lines. Taken together, our findings indicate that HIV-1 Nef protein can induce BBB disruption in the rat — presumably via MMP induction.

Performance of an Algorithm To Detect Pneumocystis carinii Pneumonia in Symptomatic HIV-Infected Persons

To determine whether an algorithm consisting of a chest radiograph and the diffusing capacity of the lung for carbon monoxide (D(LCO)) is effective in detecting Pneumocystis carinii pneumonia (PCP) in symptomatic HIV-infected persons; and to establish a benchmark for future comparisons of alternative algorithms. Prospective, 64-month study. Multicenter, ambulatory care. 306 HIV-infected subjects enrolled in the Pulmonary Complications of HIV Infection Study who developed 467 episodes of new or worsening respiratory symptoms. Chest radiography followed by D(LCO) measurement, if the radiograph was normal or unchanged. An algorithm combining a chest radiograph followed by a D(LCO) measurement, if the radiograph was normal or unchanged, was effective and detected abnormalities that led to a diagnosis of PCP in 78 of 80 evaluable episodes (97.5%). The radiograph (specific parenchymal abnormality, number of lung zones involved) and the D(LCO) (degree of decrease, degree of decrease from baseline) also provided additional information on the probability of PCP. In symptomatic HIV-infected patients suspected of having PCP, the diagnostic evaluation should begin with a chest radiograph, followed by a D(LCO) measurement, if the radiograph is normal or unchanged. If both of these tests are normal, it may be reasonable to conclude the evaluation rather than to proceed on to additional testing. This algorithm can serve as a benchmark for future comparisons.

Plasma lactoferrin levels are decreased in end-stage AIDS patients.

The antimicrobial protein lactoferrin (Lf) is present in plasma and in mucosal secretions. Using ELISA we analysed plasma and saliva of HIV-infected patients, patients with AIDS, and healthy controls for the presence of secreted Lf. The plasma Lf levels of AIDS patients (classification C3) were significantly lower (p < 0.001) as compared to asymptomatic and symptomatic HIV infected patients, or controls. In addition, plasma Lf levels closely correlated with neutrophilic granulocyte counts in the HIV-infected patients. Thus, basal plasma Lf levels are likely the result of Lf release by neutrophilic granulocytes. The Candida titres present in the oral cavity were determined in a part of the HIV-infected patient group. As it appeared, the presence of this opportunistic pathogen always coincided with low levels of salivary Lf levels. We conclude that Lf, as part of the nonspecific immune system, might play an important role in the first line of defense against opportunistic microbial infections in AIDS patients.

Oxidative DNA base damage in lymphocytes of HIV-infected drug users

In the present study, we have studied the level of oxidative DNA base damage in lymphocytes of HIV-infected intravenous drug users (IDUs) and a seronegative control group. Chromatin was isolated from the lymphocytes and then analyzed by gas chromatography/isotope-dilution mass spectrometry with selectedion monitoring (GC/IDMS-SIM). Significantly greater levels of four oxidatively modified DNA bases were observed in chromatin samples from the symptomatic HIV-infected patients than in those from the seronegative patients. These were 5-hydroxyuracil, 5-hydroxycytosine, 8-hydroxyadenine and 8-hydroxyguanine. In the case of 5-hydroxyuracil and 8-hydroxyguanine, a statistically significant difference was also found between the control group and the asymptomatic HIV-positive patients. These results suggest that oxidative stress may play an important role in the pathogenesis of acquired immune deficiency syndrome (AIDS), and that administration of antioxidant drugs to HIV-infected patients may offer protection against AIDS-related carcinogenesis.

Presence of matrix metalloproteinase-9 activity in the cerebrospinal fluid of human immunodeficiency virus-infected patients.

To determine whether matrix metalloproteinase (MMP)-9 is a potential mediator involved in the frequently detected blood-brain barrier leakage in human immunodeficiency virus (HIV)-infected patients, zymography was used to detect MMP-9 activity in cerebrospinal fluid (CSF) samples of 80 HIV-infected patients and of 10 control patients. CSF MMP-9 activity was detected in 40% of HIV-infected patients (but not in controls) and was significantly more frequent in HIV-infected patients than in those without neurologic deficits (50% vs. 13.6%). The frequency of CSF MMP-9 activity did not significantly differ between neurologically symptomatic HIV-infected patients with or without opportunistic central nervous system disease (51.6% vs. 48.1%). Additionally, the presence of CSF MMP-9 activity in HIV-infected patients was associated with an increased CSF white blood cell count and an elevated CSF-to-serum albumin ratio, suggesting that it may play a role in blood-brain/CSF barrier leakage in HIV-infected patients.

Pharmacotherapy of HIV dementia.

To review the clinical presentation and management of cognitive impairment associated with central nervous system HIV type 1 (HIV-1) infection. A MEDLINE search pertaining to HIV-related dementia (HIV-D) and pharmacologic management was performed. Additional literature was obtained from reference lists of the identified articles. All clinical trials and case reports evaluating pharmacologic efficacy in terms of clinical response, cerebrospinal fluid (CSF) changes, and neuropathology were considered for inclusion. Selection was not restricted by study design because most information consists of open uncontrolled trials and case reports. HIV-D is characterized by a triad of disturbances in cognition, motor performance, and behavior in adults. Children present with developmental delay, cognitive impairment, poor brain growth, and other neurologic symptoms. The exact pathophysiologic mechanisms of HIV-D are not known. Numerous pharmacologic agents (e.g., nucleoside reverse transcriptase inhibitors, pentoxifylline, nitroglycerin, memantine, nimodipine, peptide T) are under investigation for management of HIV-D. Zidovudine is the most thoroughly investigated medication, with patients developing HIV-D less frequently and showing improvement on neuropsychological, CSF, and neuropathologic evaluations. Sustained response to zidovudine lasts 6 months to 1 year and optimal response is achieved at higher, but less tolerated, dosages. HIV-D patients frequently have comorbid psychiatric disorders requiring psychopharmacologic agents and are sensitive to the adverse effects of these medications. HIV-D is a devastating complication of HIV-1 infection. Zidovudine is the therapy of choice for prevention and management of cognitive impairment in symptomatic HIV-infected patients and patients with AIDS. Recommendations for other medications cannot be made secondary to lack of data. The management of HIV-D may include multiple agents as more data become available regarding combination therapy. Well-designed controlled trials are needed to evaluate the efficacy of established treatments and investigational medications in the management of HIV-D.

Elevated plasma concentration of reduced homocysteine in patients with human immunodeficiency virus infection

Oxidative stress has been suggested to be an important factor in the immunopathogenesis of human immunodeficiency virus (HIV) infection. Reduced plasma thiols may lead to production of reactive oxygen species, thus contributing to the oxidative stress. We quantified the total, reduced, and protein-bound forms of the thiols homocysteine, cysteine, cysteinylglycine, and methionine in plasma from 21 HIV-infected patients and 15 healthy control subjects and compared the results with clinical and immunologic indexes. The HIV-infected patients had significantly higher concentrations of reduced homocysteine in plasma compared with control subjects. No significant differences in reduced homocysteine concentrations were noted when asymptomatic and symptomatic HIV-infected patients were compared, and we did not find any relation between reduced homocysteine concentrations and other markers of immunodeficiency. The HIV-infected patients had normal total homocysteine concentrations. The reduced cysteinylglycine concentration tended to be elevated in the patient group. No differences between HIV-infected patients and control subjects were found for reduced or total cysteine. Compared with control subjects, the HIV-infected patients had lower concentrations of methionine in plasma, and a significant correlation was found between low concentrations of methionine and low CD4+ lymphocyte counts in blood. Elevated concentrations of reduced homocysteine could possibly contribute to formation of reactive oxygen species, leading to accelerated immunologic deterioration and increased HIV replication.

Zidovudine: anno 1995.

In early 1987 treatment of symptomatic HIV-infected patients was improved by the availability and licensing of the nucleoside analogue zidovudine (ZDV, AZT, Retrovir®) as the first anti-retroviral drug in most countries of the developed world. Although more compounds have become available since then, zidovudine remains a cornerstone of therapy for HIV infection. In most countries zidovudine monotherapy is still the first choice for HIV-infected patients who have become symptomatic or who have developed a CD4 lymphocyte count beneath 500/mm3.KeywordsHuman Immunodeficiency VirusHuman Immunodeficiency Virus TypeHuman Immunodeficiency Virus InfectionZidovudine TherapyMulticenter AIDS Cohort StudyThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

A Phase I Evaluation of Concomitant Rifabutin and Didanosine in Symptomatic HIV-Infected Patients

It has been suggested that didanosine (ddI) may undergo hepatic metabolism. Rifabutin is an inducer of drug metabolism. Fifteen human immunodeficiency virus-infected patients whose conditions were stabilized on twice-daily doses of ddI participated in a Phase I, open-label, pharmacokinetic and safety drug interaction study between rifabutin and ddI. Twelve patients completed the study. All patients received their regular ddI dose (167-375 mg) on day 1. On days 2-13 they received once-daily rifabutin (600 mg, three patients; 300 mg, nine patients) with their regular twice-daily ddI regimen. On days 14-16 they received rifabutin alone. Serial blood and urine samples were collected for 12 h on day 1 and for 24 h on days 13 and 16, and safety evaluations were made throughout the study. Average day 1/day 13 ddI pharmacokinetic ratios and 95% confidence interval values for Cmax, AUC0-infinity, Cls/F, and t 1/2, lambda z were 1.17 (0.96-1.38), 1.13 (0.99-1.27), 0.91 (0.81-1.01), and 0.97 (0.79-1.15), respectively (p > 0.05 for all comparisons; paired t test). A 20% difference in AUC0-infinity could be detected with 90% power. Also, there were no significant changes in laboratory values or electrocardiograms, or in rifabutin pharmacokinetic parameters when the two agents were coadministered. Based on the safety and pharmacokinetic assessments, rifabutin did not appear to interact with ddI.