Median CD4 Lymphocyte Count Research Articles

A prognostic score for AIDS-related diffuse large B-cell lymphoma in Brazil

The aim of this study was to evaluate a prognostic score for aids-related lymphoma (ARL). A retrospective study of 104 patients with ARL treated between January 1999 and December 2007 was conducted. Diffuse large B-cell lymphoma (DLBC) was the most observed histological type (79.8%). The median CD4 lymphocyte count at lymphoma diagnosis was 125 cells per microliter. Treatment response could be evaluated in 83 (79.8%) patients, and 38 (45.8%) reached complete remission (CR); overall response rate was 51.8% (95 CI = 38.5-65.1%). After a median follow-up of 48 months, the 4-year overall survival (OS) rate among all patients was 35.8%, with a median survival time of 9.7 months (95% CI = 5.5-13.9 months). The survival risk factors observed in multivariate analysis (previous AIDS and high-intermediate/high international prognostic index (IPI)) were combined to construct a risk score, which divided the whole patient population in three distinct groups as low, intermediate, and high risk. When this score was applied to DLBC patients, a clear distinction in response rates and in OS could be demonstrated. Median disease-free survival (DFS) for patients that achieved CR was not reached, and DFS in 4 years was 83.0%. Our results show that the reduced OS observed could be explained by poor immune status with advanced stage of disease seen in our population of HIV-positive patients. Further studies will be needed to clarify the role of different treatment approaches for ARL in the setting of marked immunosuppression and to identify a group of patients to whom intensive therapy could be performed with a curative intent.

Doença pulmonar por Mycobacterium tuberculosis e micobactérias não-tuberculosas entre pacientes recém-diagnosticados como HIV positivos em Moçambique, África

Mycobacteriosis is frequently diagnosed among HIV-infected patients. In Mozambique, where few patients are under antiretroviral therapy and the prevalence of tuberculosis is high, there is need for better characterization of mycobacteria at the species level, as well as for the identification of patterns of resistance to antituberculous drugs. We studied a sample of 503 HIV-infected individuals suspected of having pulmonary tuberculosis. Of those 503, 320 tested positive for mycobacteria through sputum smear microscopy or culture of bronchoalveolar lavage fluid. Acid-fast bacilli were observed in the sputum of 73% of the individuals presenting positive cultures. Of 277 isolates tested, only 3 were nontuberculous mycobacteria: 2 were identified as Mycobacterium avium and one was identified as M. simiae. Strains initially characterized as M. tuberculosis complex through polymerase chain reaction restriction analysis (PRA) of the hsp65 gene were later confirmed as such through PRA of the gyrB gene. Among the M. tuberculosis isolates, resistance patterns were as follows: to isoniazid, 14%; to rifampin, 6%; and multidrug resistance, 5%. Previously treated cases showed significantly higher rates of resistance to first-line antituberculous drugs. The most common radiological pattern was interstitial infiltrate (in 67%), followed by mediastinal lymph node enlargement (in 30%), bronchiectasis (in 28%), miliary nodules (in 18%) and cavitation (in 12%). Patients infected with nontuberculous mycobacteria presented clinical profiles indistinguishable from those of other patients. The median CD4 lymphocyte count in this group was 134 cells/mm(3). There is a strong association between tuberculosis and AIDS in Mozambique, as expected in a country with a high prevalence of tuberculosis. Although drug resistance rates are high, the isoniazid-rifampin regimen continues to be the appropriate choice for initial therapy.

Natural polymorphisms in HIV‐1 protease: Impact on effectiveness of a first‐line lopinavir‐containing antiretroviral therapy regimen

Mutations on HIV protease lead to resistance to protease inhibitors. However, resistance development may be different according to primary, secondary or polymorphic mutations. The present study was designed to assess the impact of natural protease mutations on the effectiveness of a first-line antiretroviral therapy (ART), and secondarily, their effect on the initial viral load (VL). The study was conducted in 175 HIV-1-infected patients, who initiated a first-line lopinavir/r-containing ART regimen and who had an available genotype resistance testing before initiating therapy. We assessed the association between mutations (prevalence > or = 10%) and the initial VL. We assessed the association between mutations and ART effectiveness using two surrogate markers: the slope of VL decrease at 1 month and the time to VL undetectability. For the 175 patients, the initial median VL was 4.94 log(10) copies/ml [interquartile range: 4.44-5.47] and the initial median CD4 lymphocyte count, 219/microl [129-296]. Eighteen mutations had a prevalence > or = 10%. At 1 month, the median VL decrease was 2.35 log(10) copies/ml [1.76-2.82]. The median time to VL undetectability was 128 days [91-196]. No mutation was associated significantly with the initial VL, the slope of VL decrease at 1 month or the time to VL undetectability. This study of antiretroviral-naive patients showed that protease polymorphisms had no impact on the effectiveness of a lopinavir/r-containing ART regimen. However, polymorphisms may affect ART effectiveness differently in other populations, such as ART-experienced patients and/or patients treated with protease inhibitors other than the one used here.

The Impact of Episodic CD4 Cell Count-Guided Antiretroviral Therapy on Quality of Life

To evaluate the effect of episodic antiretroviral therapy on quality of life (QOL). This was a substudy of the Strategies of Management of Antiretroviral Therapy study, in which patients were randomized to continuous versus CD4 cell count-guided episodic antiretroviral therapy. QOL assessments included an analog scale for current health and the Short-Form 12 Item Survey, a standard abbreviated QOL instrument. A total of 1225 patients had QOL assessments over a mean follow-up time of 2.4 years. Most (76%) were on antiretroviral therapy at enrollment; the median CD4 lymphocyte count was 575 (interquartile range: 455 to 784) cells/mm3; and mean current health was 75 on a scale from 0 to 100, and 50% reported very good or excellent general health. Through follow-up, whenever QOL outcomes differed, the results were inferior among patients in the episodic therapy group compared with the continuous therapy group (current health, Physical Health Component Score [both P = 0.05], general health perceptions, physical functioning, and energy [all P = 0.03]). HIV disease progression (opportunistic disease or death) was more common in the episodic therapy arm and was preceded by marked declines in QOL, but excluding participants with disease progression had minimal effect on QOL comparisons. CD4 count-guided episodic use of antiretroviral therapy resulted in inferior QOL compared with continuous therapy.

Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus‐associated diffuse large B‐cell lymphoma: results of a phase II trial

Immunochemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) is the standard treatment in non-immunosuppressed patients with diffuse large B-cell lymphoma (DLBCL), but its adequacy has not been definitively established in patients with human immunodeficiency virus (HIV)-related lymphoma. This phase II trial aimed to evaluate the safety and efficacy of six cycles of R-CHOP in patients with HIV-related DLBCL and to determine whether response to highly active antiretroviral therapy (HAART) had prognostic impact. Patients were eligible if they had performance status <3 and absence of active opportunistic infections. Eighty-one patients were enrolled, 57 in stages III or IV, International Prognostic Index (IPI) 0 or 1 (n = 26), 2 (n = 19), 3 (n = 20) and 4 or 5 (n = 16), and median CD4 lymphocyte count of 0.158 x 10(9)/l. The main adverse events were neutropenia (48% of cycles) and infections (10% of cycles), which were fatal in seven patients. Complete response was achieved in 55 (69%) patients, with an estimated 3-year disease-free survival of 77% and 3-year overall survival of 56%. IPI score and virological response to HAART were the prognostic parameters for response and survival. In HIV-related DLBCL R-CHOP is feasible, safe and effective. The prognosis depends on lymphoma-related parameters and on the response to HAART.

HIV in the Workplace in Botswana: Incidence, Prevalence, and Disease Severity

Few detailed epidemiologic data exist regarding the impact of HIV infection on the workplace in the developing world. In addition, most HIV surveys examine only prevalence, without data on incidence or disease severity. In June 2003, we conducted a voluntary anonymous HIV serosurvey among employees of the Debswana Mining Company, the largest nongovernmental employer in Botswana. Among the 3558 participants, annual HIV incidence was estimated to be 3.4%, and HIV prevalence was 23.8%. HIV-infected participants had a median CD4(+) lymphocyte count of 427 cells/mm(3) (interquartile range 269-642), with 13.3% of samples <200 cells/mm(3). The high incidence and prevalence of HIV, and the proportion of workers with <200 CD4(+) lymphocytes/mm(3), demonstrate the impact of HIV infection in this workplace and the potential negative impact on productivity. These results highlight the need for routine HIV testing and access to antiretro-viral treatment for workers in countries such as Botswana.

Combination antiretroviral therapy without a nucleoside reverse transcriptase inhibitor: experience from 334 patients in three cohorts.

Toxicity and resistance may limit the use of HIV nucleoside reverse transcriptase inhibitors (NRTIs). We assessed the safety and activity of regimens that did not include an NRTI. We analysed NRTI-sparing regimens using pooled data from three cohorts in Australia and France where HIV RNA viral load, CD4 lymphocyte count and metabolic parameters are assessed prospectively. The inclusion criterion was the commencement of any antiretroviral combination excluding NRTIs. A total of 334 (3.9%) of 8477 patients were included in the present study for a median follow-up time of 105 weeks. Therapeutic combinations were one nonnucleoside reverse transcriptase inhibitor (NNRTI) plus one protease inhibitor (PI) (58%), two PIs (26%), one PI (16%), and one NNRTI plus two PIs (8%). At baseline, the median CD4 lymphocyte count was 264 cells/muL (interquartile range 164-446 cells/muL) and 25% of patients had plasma HIV RNA below 500 HIV-1 RNA copies/mL. In intent-to-treat analysis, 64% of patients had HIV RNA <500 copies/mL at 6 months and 68% at 24 months. The mean CD4 lymphocyte count increase was 60 cells/microL (95% confidence interval 41-76 cells/microL) at 6 months and 111 cells/microL (95% confidence interval 82-140 cells/microL) at 24 months. Prognostic factors for having HIV RNA <500 copies/mL at 6 months included independently having undetectable HIV RNA at baseline and being naïve for NNRTIs. The proportion of patients with triglycerides >2.3 mmol/L increased from 32% to 63% at 6 months and to 62% at 24 months (P-trend=0.002), and those with total cholesterol >6.2 mmol/L increased from 18% to 38% at 6 months and to 44% at 24 months (P-trend <0.001), with an increased risk for patients treated with NNRTI+PIs. Forty-one per cent of patients discontinued their NRTI-sparing regimen. In these antiretroviral-experienced patients, NRTI-sparing therapy appeared to have satisfactory virological and immunological efficacy. However, hyperlipidaemia was frequent and requires monitoring of cardiovascular risk factors.

Results of treatment with doxorubicin, bleomycin, vinblastine and dacarbazine and highly active antiretroviral therapy in advanced stage, human immunodeficiency virus-related Hodgkin's lymphoma

Although doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is considered the standard chemotherapy regimen for Hodgkin's lymphoma (HL), information on the results of this therapy in human immunodeficiency (HIV)-related HL is scarce. We analyzed the results of the ABVD regimen and highly active antiretroviral therapy (HAART) in patients with advanced stage, HIV-related HL. From January 1996 to December 2005, 62 HIV-infected patients with newly diagnosed HL were treated in 15 Spanish hospitals. Six to eight cycles of ABVD and HAART were planned. Response to chemotherapy, overall survival (OS) and event-free survival (EFS) were recorded. The median age of the patients was 37 years (range, 24-61) and 29 (47%) had a previously known diagnosis of acquired immunodeficiency syndrome. The median CD4 lymphocyte count at diagnosis was 129/muL (range 5-1,209). The histologic subtype of HL was nodular sclerosis in 17 patients (27%), mixed cellularity in 25 (41%), lymphocyte depletion in 10 (16%) and non-specified in the remaining 10 (16%). Twenty-one (34%) patients were in stage III and 41 (66%) in stage IV. The scheduled six to eight ABVD cycles were completed in 82% of cases. Six patients died during induction, 54 (87%) achieved a complete response (CR) and two were resistant. After a median follow-up of 39 and 47 months, 5-year EFS and OS probabilities were 71% (47-95) and 76% (65-87), respectively. An immunological response was observed in 24 out of 43 patients (56%) and a virological response in 27 out of 40 (68%). The immunological response to HAART had a positive impact on OS and EFS (p=0.002 and p=0.001, respectively). In patients with advanced stage, HIV-related HL, treatment with ABVD together with HAART is feasible and effective. This supports the concept that patients with HIV-related HL should be treated in the same way as immunocompetent patients if HAART, adequate supportive therapy and anti-infectious prophylaxis are given concomitantly. An immunological response to HAART has a positive impact on OS and EFS.

Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial

To demonstrate a causal relationship between herpes simplex virus 2 (HSV-2) and increased genital HIV-1-RNA shedding in women on HAART. A randomized, double-blind, placebo-controlled trial of herpes-suppressive therapy (valacyclovir 500 mg twice a day) in HIV-1/HSV-2-infected women taking HAART in Burkina Faso. Participants were followed for a total of 12 biweekly visits before and after randomization. The presence and frequency of genital and plasma HIV-1 RNA, and of genital HSV-2 were assessed using summary measures, adjusting for baseline values. Random effect linear regression models were used to assess the impact of treatment on genital and plasma viral loads among visits with detectable virus. Sixty women were enrolled into the trial. Their median CD4 lymphocyte count was 228 cells/mul, and 83% had undetectable plasma HIV-1 RNA at baseline. Valacyclovir reduced the proportion of visits with detectable genital HSV-2 DNA [odds ratio (OR) 0.37, 95% confidence interval (CI) 0.13, 1.05], but had no significant impact on the frequency (OR 0.90, 95% CI 0.31, 2.62) or quantity (reduction of 0.33 log copies/ml, 95% CI -0.81, 0.16) of genital HIV-1 RNA. However, according to pre-defined secondary analyses restricted to women who shed HIV-1 at least once in the baseline phase, valacyclovir reduced both the proportion of visits with detectable HIV-1 shedding (OR 0.27, 95% CI 0.07, 0.99) and the quantity of genital HIV-1 RNA during these visits (-0.71 log10 copies/ml, 95% CI -1.27, -0.14). HSV-2 facilitates residual genital HIV-1 replication among dually infected women taking HAART despite HIV-1 suppression at the systemic level.

Treatment with Rituximab, CHOP and Highly Active Antiretroviral Therapy (HAART) in AIDS-Related Diffuse Large B-Cell Lymphomas (DLBCL). Study of 60 Patients.

Background and objective. Rituximab and CHOP (R-CHOP) is the most employed treatment for DLBCL, but pts with AIDS-related lymphomas are usually excluded from clinical trials. The objective of this open, prospective multicenter trial is to evaluate the feasibility, efficacy and toxicity R-CHOP and HAART in AIDS-related DLBCL.Patients and methods. Between April 2001 and July 2005, 60 consecutive HIV-infected pts with newly diagnosed DLBCL were included in 20 Spanish hospitals. HAART was given to all patients from diagnosis if they were not already receiving it. Six cycles of R-CHOP were administered, IT CNS prophylaxis (MTX, ARA-C and hydrocortisone) was given in every cycle to all patients. G-CSF support was recommended Response to chemotherapy, toxicity, OS and DFS for complete responders were recorded.Results. Median age 42 yr (range 26–64), 49 (82%) males, 30 (50%) with previous known diagnosis of HIV infection (median from dx HIV to NHL 10 yr, range 0.5–19). Median CD4 lymphocyte count 152/mL (range 0–905), median HIV load 19x103 copies/mL (range 0–2x106). 36 pts were receiving HAART at the time of NHL dx (median 3.5 yr, range 0.5–9). Extranodal involvement 43 (72%), stage III-IV 38 (63%) and 36/56 had intermediate-high or high age-adjusted IPI score. 10 patients are under treatment, 1 (2%) withdrawal, 6 (12%) induction death (infection 3, hepatic failure 2, multiorgan failure 1), 10 (20%) resistant, CR 33 (66%). After a median follow-up of 2 yr, 2-yr survival probability was 63% (95%CI 50–76). The probability of remaining alive and in first CR at 2 yr for complete responders was 89% (95%CI 77–100). Three patients died in first CR (opportunistic infection, sudden death and violent death) and no relapses have occurred to date. Virologic and immunologic responses to HAART at 6 months after the completion of treatment were maintained or achieved in 17/21 (81%) and 14/22 (64%) of patients, respectively. Out of 245 R-CHOP cycles analysed the most frequent grade II-IV toxicities were infections (30, 12%), gastrointestinal (21, 9%) and neurologic (5, 2%).Conclusion. In patients with AIDS-related DLBCL the combination of HAART and R-CHOP is feasible and effective. In this trial the response rate and survival are comparable to those obtained in immunocompetent patients treated with R-CHOP.

Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine

To evaluate the steady state pharmacokinetics of nevirapine (NVP) in HIV-infected children receiving a fixed-dose combination of stavudine, lamivudine and NVP. This cross-sectional study enrolled 34 children (18 girls) who had received GPO-VIR S30 (30 mg stavudine, 150 mg lamivudine and 200 mg NVP) for at least 8 weeks. Tablets were divided into quarter fractions (1/4, 1/2, 3/4 or 1 tablet) to attain the NVP dosages of 120-200 mg/m every 12 h. Plasma NVP levels were measured at predose, and at 2 and 6 h after drug administration. The median age was 8.4 years (range, 3-15). Median CD4 lymphocyte count and percentage at study entry was 576 x 10 cells/l and 20.25%, respectively. The median pharmacokinetics parameters were area under the curve at 12 h, 78.4 h x mug/ml; minimum plasma drug concentration, 5.98 microg/ml; plasma half-life, 25.5 h; apparent oral clearance, 0.079 l/kg per h; and volume of distribution, 2.95 l/kg. Only one child had a minimum plasma drug concentration < 3.4 microg/ml (2.57 microg/ml). Of the 13 children who received GPO-VIR as their first-line regimen, 12 had plasma HIV-1 RNA < 400 copies/ml at 6-18 months, with a median CD4 lymphocyte increase of 216 and 433 x 10 cells/l at 6 and 12 months of treatment, respectively. The administration of GPO-VIR S30 fixed-dose combination tablets in fractions or as a whole tablet to children resulted in appropriate NVP exposure and satisfactory virological and immunological benefit. This finding confirms the effectiveness of using a fixed-dose combination as a "transitional option" while waiting for a paediatric fixed-dose combination drug formulation.

GB Virus C Infection in Children With Perinatal Human Immunodeficiency Virus Infection

GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome. To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab). The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.5-8.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4 lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab. GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small.

The Epidemiology of Intestinal Microsporidiosis in Patients with HIV/AIDS in Lima, Peru

We studied microsporidiosis in human immunodeficiency virus-positive patients in 2 Lima hospitals. Of 2652 patients, 66% were male, 6% received antiretroviral therapy (ART), and the median CD4 lymphocyte count was 131 cells/microL. Sixty-seven patients (3%) had microsporidiosis; stool specimens from 56 were identified as having Enterocytozoon bieneusi of 10 different genotypes. The 2 most common genotypes, Peru-1 and Peru-2, were not associated with significant increases in chronic diarrhea; other genotypes were associated with a 4-fold increased risk. Risk factors for E. bieneusi infection segregated by genotype: contact with duck or chicken droppings and lack of running water, flush toilet, or garbage collection with genotype Peru-1 and watermelon consumption with other genotypes. Shortened survival was associated with low CD4 lymphocyte count (P<.0001), no ART (P<.0001), and cryptosporidiosis (P=.004) but not with microsporidiosis (P=.48). Our data suggest the possibility of zoonotic E. bieneusi transmission and an association with poor sanitary conditions.

Occurrence of Gastrointestinal Opportunistic Disorders in AIDS Despite the Use of Highly Active Antiretroviral Therapy

Since the introduction of highly active antiretroviral therapy (HAART), the frequency of opportunistic disorders (ODs) of the gastrointestinal (GI) tract in human immunodeficiency virus (HIV)-infected patients has fallen dramatically. We have found, however, that despite the use of HAART, HIV-infected patients can still present with GI ODs. To evaluate the prevalence of GI ODs in HIV-infected patients on HAART who were undergoing endoscopic evaluation for GI-related symptoms. From January 1996 through February 2002, all HIV-infected patients undergoing GI endoscopy were prospectively identified; mucosal biopsies were obtained in a standardized fashion and histologic specimens were examined by a single GI pathologist. All the patients on HAART presenting with a GI OD are described. Results showed that 294 patients (88% men; mean age, 36.5 +/- 10 years; median CD4 lymphocyte count, 64 cells/microl; range, 1-884; median viral RNA level, 40,357 copies/ml; range, 0-7,721,715) underwent 401 upper and/or lower endoscopies during the study period. The use of HAART increased from 10% in early 1996 to 85% in 2002. Nevertheless we found that 27 patients (9%) presented with a GI OD despite HAART. Forty percent of the patients with a GI OD were noncompliant with HAART. We conclude that GI ODs can occur despite HAART and normal CD4 counts. The prevalence of GI ODs in HIV-infected patients taking HAART is 9%. The reasons for this are multifactorial and likely include noncompliance with medications, viral resistance to the drugs, and decreased drug bioavailability. Although the use of HAART has led to a decreased incidence of GI ODs in AIDS, the gastroenterologist evaluating these patients should not discard the possibility that the GI symptoms in HIV-infected patients taking HAART may be secondary to an OD, even when the CD4 count is normal and the viral load is low.

Hepatitis C virus viral recurrence and liver mitochondrial damage after liver transplantation in HIV–HCV co-infected patients

As life expectancy in HIV-HCV co-infected patients improves, end stage liver disease requiring liver transplantation (LT) may become an emerging problem. We report the Paul Brousse Hospital experience of transplantation for end stage cirrhosis in HIV-HCV co-infected patients. Seven consecutive HIV-HCV co-infected patients were transplanted between December 1999 and December 2002 for end stage liver disease due to HCV. All patients were treated by highly active antiretroviral therapy (HAART), HIV plasma viral load was <400 copies/ml and median CD4 lymphocyte count was 306 cells/mm3 (range, 103-510) before LT. At the time of evaluation (March 2003), the median follow-up was 21 months (range, 4-40). Two patients died, 4 and 22 months, respectively after LT. At the last biopsy, METAVIR score was staged F4 in two patients, F3 in two, and F1 in one. Microvesicular steatosis was noted in nearly all patients. The ratio of mitochondrial to nuclear DNA was low in three of four patients examined as compared with the amount of liver mtDNA found in eight HIV-negative, HCV-infected controls (P=0.01). A significant defect in the activity of the respiratory chain complex IV was noted in all five patients studied. Mitochondrial hepatotoxicity and severe HCV recurrence occur in HIV-HCV co-infected patients after LT.

Etiologies and Manifestations of Persistent Diarrhea in Adults with HIV‐1 Infection: A Case‐Control Study in Lima, Peru

OBJECTIVE We sought to determine the etiologies, manifestations, and risk factors for persistent (> or =7 days) diarrhea in human immunodeficiency virus type 1 (HIV-1)-infected persons in Peru. The present study is a case-control study of 147 HIV-1-infected case subjects with persistent diarrhea and 147 HIV-1-infected control subjects without diarrhea. We obtained clinical, demographic, and exposure data, CD4 lymphocyte counts, and stool samples for detection of enteric parasitic and bacterial pathogens and rotavirus. One or more enteric pathogen was identified in 55% of case subjects and 21% of control subjects (odds ratio adjusted for CD4 lymphocyte count, 3.8; 95% confidence interval, 2.2-6.5). The median CD4 lymphocyte count was highest with pathogen-free diarrhea and lowest with Cryptosporidium infection. Cryptosporidium species (the most frequent pathogen), Giardia lamblia, Aeromonas species, Campylobacter species, and rotavirus were all significantly associated with diarrhea. Bacterial pathogens were significantly associated with G. lamblia and rotavirus infection. Of the bacterial pathogens (Aeromonas, Campylobacter, Salmonella, and Vibrio species and enterotoxigenic Escherichia coli), only 24% were susceptible to cotrimoxazole, whereas 90% were susceptible to ciprofloxacin. In no case did the sensitivity or positive predictive value of specific clinical and laboratory findings for curable enteric infections exceed 50%. Several enteric pathogens were associated with diarrhea in HIV-1-infected case subjects in Peru, especially among those who were heterosexual. Clinical findings were poor predictors of detectable microbial etiology. The guidelines for initial management of chronic diarrhea with sulfamethoxazole-trimethoprim in HIV-1-infected persons require revision, at least in settings where prophylaxis with this agent is common.

The unmasking of Pneumocystis jiroveci pneumonia during reversal of immunosuppression: case reports and literature review

BackgroundPneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.Case presentationWe aim to better define this unique clinical syndrome by reporting two cases of PCP manifesting acutely with respiratory failure during reversal of immunosuppression in non-HIV infected patients, and reviewed the relevant literature. We searched our databases for PCP cases manifesting in the context of IRD according to our predefined case definition, and reviewed the case notes retrospectively. A comprehensive search was performed using the Medline database of the National Library of Medicine for similar cases reported previously in the English literature in October 2003. A total of 28 non-HIV (excluding our present case) and 13 HIV-positive patients with PCP manifesting as immunorestitution disease (IRD) have been reported previously in the literature. During immunorestitution, a consistent rise in the median CD4 lymphocyte count (28/μL to 125/μL), with a concomitant fall in the median HIV viral load (5.5 log10 copies/ml to 3.1 log10 copies/ml) was observed in HIV-positive patients who developed PCP. A similar upsurge in peripheral lymphocyte count was observed in our patients preceding the development of PCP, as well as in other non-HIV immunosuppressed patients reported in the literature.ConclusionsPCP manifesting as IRD may be more common than is generally appreciated. Serial monitoring of total lymphocyte or CD4 count could serve as a useful adjunct to facilitate the early diagnosis and pre-emptive treatment of this condition in a wide range of immunosuppressed hosts, especially in the presence of new pulmonary symptoms and/or radiographic abnormalities compatible with the diagnosis.

A systematic review of the clinical significance of pulmonary Mycobacterium kansasii isolates in HIV infection.

Guidelines recommend treating HIV-infected patients with pulmonary Mycobacterium kansasii infection only in the presence of multiple positive cultures and clinical and radiographic abnormalities. Some authors suggest a single positive culture warrants treatment. A systematic literature review was done to determine whether HIV-infected patients who had M. kansasii isolated from respiratory specimens may have an indolent infection (often referred to as colonization) not requiring treatment and to determine the utility of diagnostic criteria in distinguishing disease from indolent infection. Sixteen studies were included, with at least 573 patients: mean age 44 years; 91% male; 64% men who had sex with men; 35% injection drug users; and median CD4 lymphocyte count of 2-381 cells/microL. The median rate of indolent infection was 8%. Of the few patients who did not satisfy diagnostic criteria and were left untreated, outcomes were generally favorable. Overall, survival was longer in treated patients (mean 12 vs. 4 months). Indolent pulmonary infection with M. kansasii may exist in the setting of HIV, but published data do not provide adequate information to identify such patients. It is unclear whether unfulfilled diagnostic criteria necessarily imply the absence of disease in this context.

Prospective comparison of brush cytology, viral culture, and histology for the diagnosis of ulcerative esophagitis in AIDS

Background & Aims: The best method(s) for the diagnosis of esophageal ulcers in patients with acquired immune deficiency syndrome (AIDS) is unknown. Methods: Over an 8-year period, all human immunodeficiency virus (HIV)-infected patients with a CD4 lymphocyte count of ≤250/mm 3 and an esophageal ulcer underwent a standard protocol consisting of 2 biopsy examinations for viral culture (shell vial technique), brushing for cytology with immunohistochemistry (IHC) for viral antigens, and 10 biopsy examinations of the ulcer base/edge for routine histology and IHC. The cause of ulcer was based on histologic findings and clinical and endoscopic follow-up evaluation after therapy. Results: Forty patients with 48 episodes of ulcer were studied (mean age, 34 yr; 88% men; median CD4 lymphocyte count = 31 cells/mm 3; range, 0–250 cells/mm 3). Six patients had more than one endoscopic examination documenting ulcer, and 2 patients had more than one cause of ulcer. The most common causes of ulcer were: idiopathic (IEU) 22, cytomegalovirus (CMV) 15, and gastroesophageal reflux disease 6. Viral culture was positive for herpes simplex in 3 of 3, but only 4 of 15 (27%) for CMV, and specificity of viral culture was 100%. Cytologic brushings were only positive in the patients with herpes simplex virus (HSV) or incidental Candida esophagitis. Viral cytopathic effect was apparent on routine histologic staining in each patient with viral esophagitis, and IHC confirmed the diagnosis in each patient. Follow-up evaluation disclosed no patient with a misdiagnosis based on histology. Conclusions: Viral culture and cytologic brushings add little to the evaluation of esophageal ulcers in patients with AIDS over multiple biopsy specimens with routine histology.

Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa.

A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count < 200 x 10 cells/l. The programme used standardized protocols (using generic medicines whenever possible), a team-approach to clinical care and a patient-centred approach to promote adherence. Two-hundred and eighty-seven adults naive to prior ART were followed for a median duration of 13.9 months. The median CD4 lymphocyte count was 43 x 10 cells/l at initiation of treatment, and the mean log10 HIV RNA was 5.18 copies/ml. The HIV RNA level was undetectable (< 400 copies/ml) in 88.1, 89.2, 84.2, 75.0 and 69.7% of patients at 3, 6, 12, 18 and 24 months respectively. The cumulative probability of remaining alive was 86.3% at 24 months on treatment for all patients, 91.4% for those with a baseline CD4 lymphocyte count > or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.