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CD8+ lymphocyte counts and the risk of death in advanced HIV infection.

BACKGROUND: Mortality related to human immunodeficiency virus (HIV) infection occurs predominantly in patients with CD4+ lymphocyte counts of less than 50 cells/mm3. We followed 133 HIV-infected patients with enrollment CD4 counts of less than 50 cells/mm3 to determine if the risk of death during a 1-year period could be predicted by a single enrollment CD8+ lymphocyte count. METHODS: Enrollment data including age, sex, T-cell subset counts, p24 antigen status, antiretroviral use, and preexisting HIV-related illnesses were collected on a cohort of 133 consecutive patients with enrollment CD4 counts of less than 50 cells/mm3. The cohort was followed for 1 year, and survival data were analyzed in relation to enrollment variables. RESULTS: The mean enrollment CD8 count of those patients alive at 1 year was 600 cells/mm3, compared with a mean enrollment CD8 count of only 370 cells/mm3 in patients who had died prior to 1 year (P < .001). For every 100-cell decline in the enrollment CD8 count, the risk of death increased by 16% (95% confidence interval [CI], 5% to 22%), independent of other enrollment variables, including CD4 counts and p24 antigen status. A significant CD8 count warning level of 415 cells/mm3, irrespective of the presence of other enrollment variables, was associated with death within 1 year. The Kaplan-Meier estimated chance of death within 1 year was 54% (95% CI, 42% to 66%) for patients with CD8 counts of less than 415 cells/mm3 compared with only 25% (95% CI, 14% to 36%) for patients with CD8 counts greater than 415 cells/mm3. CONCLUSIONS: This study finds that a single CD8 count has important prognostic significance in patients with advanced HIV infection and suggests that potential therapies to enhance CD8 counts might be beneficial to patients with advanced HIV infection.

Acquired Immunodeficiency Syndrome↗

Effect of clinical events on plasma HIV-1 RNA levels in persons with CD4+ T-lymphocyte counts of more than 500 x 10(6) cells/l.

OBJECTIVE: Immune stimulation of CD4 lymphocytes is thought to enhance HIV-1 replication in vivo. Therefore, we sought to define the impact of clinical events identified as putative immune activators on the variability of plasma HIV-1 RNA levels in persons with CD4 cell counts greater than 500 x 10(6) cells/l. DESIGN: We prospectively recorded clinical events and measured plasma HIV-1 RNA levels weekly for 24 weeks in 16 HIV-1-infected adults who were not receiving antiretroviral therapy and who had CD4 cell counts greater than 500 x 10(6) cells/l. METHODS: Standard weekly interviews were conducted to capture potential immune activators (e.g., infections, immunizations, and allergic reactions). All plasma HIV-1 RNA levels were measured using the Amplicor HIV-1 Monitor assay (Roche Diagnostics, Branchburg, New Jersey, USA) according to the manufacturer's instructions. RESULTS: Participants had remarkably stable viral loads during the 6 month study period. Infections were significantly more frequent during the 7 days prior to individual HIV-1 RNA measurements that exceeded the assay variation thresholds determined for this study (+/- 0.324 log) than during the comparable time periods preceding stable measurements (P = 0.023). As a group, the eight participants who had one to four HIV-1 RNA measurements that exceeded the thresholds experienced more infections and declining CD4 cell counts over the study course compared to the eight participants whose measurements all fell within the thresholds (P = 0.058 and 0.053 respectively). CONCLUSIONS: Our study suggests that in untreated HIV-1-infected persons with CD4 cell count greater than 500 x 10(6) cells/l, viral load is generally quite stable, although acute minor infections are associated with transient fluctuations generally lasting no more than 1 week.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus and the trauma patient: factors influencing postoperative infectious complications.

OBJECTIVE: While immunosuppression 2 degrees to human immunodeficiency virus (HIV) infection should logically render HIV+ trauma victims more prone to infection after injury, little data is available regarding trauma outcome in this group of patients. Since the helper CD4+ lymphocyte count is a marker for progression of HIV-associated diseases, we examined the relationship between CD4+ counts, Injury Severity Score (ISS), and bacterial infectious complications in HIV+ trauma patients. METHOD: Retrospective review of 56 consecutive HIV+ trauma patients treated at a Level I trauma center. RESULTS: Nine patients (15%) developed significant infectious complications (four pneumonias, three soft-tissue infections, one urinary tract infection, one wound infection) with no pattern to the causative agents. Evaluation of CD4+ counts, white blood cell counts, serum albumin levels, blood transfusion requirements, and ISS revealed that only the ISS was associated with infectious complications. CONCLUSION: Despite the profound immunosuppression in this group of patients, the incidence of bacterial infectious complications was independent of the CD4+ count (p = 0.958), but was associated with increases in the ISS (p = 0.003).

Adult↗

Markov modelling of immunological and virological states in HIV-1 infected patients.

The purpose of this study was to evaluate the evolution of HIV infected patients and to bring out some significant factors associated with this pathology. The main criteria revealing the State of illness is viral load measurement (VL). However the CD4 lymphocytes also represent an important marker as these reflect the State of the immune reservoir. Many studies have been carried out in this field and different models have been proposed with a view to a better understanding of this disease. Multi State Markov models defined in terms of CD4 counts, or in terms of viral load, have proved to be very useful tools for modelling HIV disease progression. The model we have developed in this study is based on both the CD4 lymphocytes counts and VL. Markov models are characterized by transition intensities. In this paper we explored several structures in succession. First, we used a homogeneous continuous time Markov process with four states defined by crossed values of CD4 and VL in a given patient at a given time. Then, the effect of certain covariates on the infection process was introduced into the model via the transition intensity functions, as with a Cox regression model. Since the hypothesis of homogeneity may be unrealistic in certain cases, we also considered piecewise homogeneous Markov models. Finally, the effects of covariates and time were combined in a piecewise homogeneous model with a covariate. We applied these methods to data from 1313 HIV-infected patients included in the NADIS cohort.

Age Factors↗

Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy.

BACKGROUND: Enterocytozoon bieneusi and Cryptosporidium parvum cause chronic antimicrobial-resistant gastrointestinal infections in HIV-1-infected individuals. HIV-1 reverse transcriptase inhibitors delay the onset of opportunistic infections, but are not known to reverse established infections. HIV-1 protease inhibitors are more effective across a broader range of HIV-1-infected immune cells. Combination antiretroviral therapy that includes a protease inhibitor could improve immunity to E bieneusi and C parvum. METHODS: HIV-1 infected patients with chronic microsporidiosis (five), cryptosporidiosis (three), or dual infection (one), were treated with combination therapy that included at least one HIV-1 protease inhibitor. Outcome measures were symptoms, weight, use of antidiarrhoeal and antimicrobial drugs, T-lymphocyte subsets, HIV-1 viraemia, stool microscopy, and biopsy by endoscopy. FINDINGS: All patients had complete clinical responses, gained a median 15 kg in weight, and ceased all antidiarrhoeal and antimicrobial therapies. Biliary cryptosporidiosis responded in both affected patients. Neither pathogen was detected in follow-up stool microscopy (eight of eight patients) or in biopsy samples by endoscopy (five of five). Intestinal architecture returned to normal in three patients. There was a dense CD8 lymphocyte and macrophage infiltrate and staining of intraepithelial E bieneusi with interferon-gamma before and after treatment, but little staining for CD4 or B lymphocytes, interleukin 10, or HIV-1 gp41. Five patients remained symptom-free after a median 13 months follow-up. Four patients had recurrent diarrhoea at 7-13 months (one with positive stool microscopy), associated with declining CD4 counts. INTERPRETATION: Combination antiretroviral therapy that includes a protease inhibitor can restore immunity to E bieneusi or C parvum in HIV-1 infected individuals, and result in complete clinical, microbiological, and histological responses. The persistent CD8 cell and macrophage infiltrate, and the rapid time to relapse in patients with declining CD4 lymphocyte counts, suggest that neither infection was eradicated.

AIDS-Related Opportunistic Infections↗

Stavudine in patients with AIDS and AIDS-related complex: AIDS clinical trials group 089.

In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safety were assessed in 41 patients treated with dosages of 0.5-12.0 mg/kg/day. Among evaluable patients, 10% increases in CD4 lymphocyte counts were sustained in 24 (60%) of 40 during treatment; an NAUC response (normalized area under the CD4 cell count-versus-time curve > 1.0) was observed in 31 (91%) of 34 at 10 weeks and in 20 (80%) of 25 at 24 weeks; 15 (83%) of 18 had decreases in p24 antigenemia; and 24 (60%) of 40 gained > or = 2.5 kg body weight. Median CD4 lymphocyte levels remained above baseline for 6 months in patients receiving > 0.5 mg/kg/day. Median serum p24 antigen levels remained below baseline for > or = 1 year in patients with p24 antigen responses. The principal toxicity was peripheral neuropathy, which generally resolved after drug discontinuation but limited the dosage to < or = 2.0 mg/kg/day. Additional trials assessing the effect of stavudine on overall morbidity and mortality are ongoing.

AIDS-Related Complex↗

Markers of HIV infection in the Concorde trial. Concorde Co-ordinating Committee.

The Concorde trial compared immediate (Imm) with deferred (Def) AZT monotherapy in asymptomatic HIV-positive participants. Haematological and immunological markers and weight were measured throughout, and correlated with clinical endpoints. Markers associated with disease progression (CD4 lymphocyte count and percentage, platelets, p24 antigen and beta 2 microglobulin favoured Imm: those associated with toxicity (haemoglobin, neutrophils and white cell count) favoured Def. CD8 and total lymphocyte count did not differ significantly between groups. In multivariate analysis, the combination of baseline CD4, p24 antigen and beta 2m was the best baseline predictor of disease. Including change in CD4 and beta 2m at 12 weeks, or changes over follow-up in these markers significantly improved the fit. Markers were also incorporated into the definition of 'clinical' endpoints. Hazard ratio estimates from end-points that included CD4 < 50 and CD4 < 25 were closest to those for AIDS or death alone, but added very few extra events. Use of other landmark CD4 counts (100 or greater) or relative decreases in counts (25% or more) increased the number of events, but overestimated the effect of immediate AZT. Although AZT had a beneficial effect on the surrogate markers of efficacy evaluated, these changes did not predict clinical outcome, nor could the markers be usefully incorporated into an endpoint definition.

Anti-HIV Agents↗

Diagnosing HIV-related disease: using the CD4 count as a guide.

OBJECTIVE: To summarize current information on the relation between CD4 counts and the risk of different HIV-related diseases. MEASUREMENTS AND MAIN RESULTS: MEDLINE search of English language articles between 1985 and 1996 using the medical subject heading (MeSH) term "CD4 lymphocyte count" and searches using key words of multiple HIV-related diseases were conducted. Some HIV-related diseases can be stratified to different CD4 count levels. Regardless of their CD4 count, HIV-infected patients are susceptible to sinusitis, Kaposi's sarcoma, community-acquired pneumonia, and oral hairy leukoplakia. In advanced HIV, when CD4 is below 200/mm3, Pneumocystis carinii pneumonia, toxoplasmosis, progressive multifocal leukoencephalopathy, Mycobacterium avium complex, molluscum contagiosum, and bacillary angiomatosis all increase in incidence. In very advanced HIV disease, when CD4 counts are below 50/mm3, patients are at risk of pseudomonas pneumonia, cytomegalovirus retinitis, central nervous system lymphoma, aspergillosis, and disseminated histoplasmosis.

AIDS-Related Opportunistic Infections↗

Association of syncytium-inducing phenotype of HIV-1 with CD4 cell count, viral load and sociodemographic characteristics.

OBJECTIVES: To study whether syncytium-inducing (SI)/non-SI (NSI) phenotype of HIV-1 is associated with CD4+ lymphocyte count, plasma HIV RNA level, clinical stage and sociodemographic characteristics in antiretroviral-naive HIV-1-infected patients. DESIGN: Cross-sectional analysis of single centre cohort study data. METHODS: SI/NSI phenotype was determined using a cocultivation assay using patients' peripheral blood mononuclear cells and MT2 cells. Standard procedures were used for CD4+ cell counts and viral load measurements in plasma. Univariate and multivariate analyses of association of CD4+ cell counts, viral load, clinical stage, age, sex and mode of HIV transmission were performed. RESULTS: In univariate analysis, SI phenotype was significantly associated with lower CD4+ cell counts, higher HIV RNA plasma levels, symptomatic HIV disease, male sex and age 32-36 years (middle tercile). In multivariate analysis, only lower CD4+ cell counts were associated with SI phenotype (odds ratio per increase of 100 x 10(6)/l, 0.54; 95% confidence interval, 0.38-0.78). CONCLUSIONS: HIV-1 SI phenotype was associated with lower CD4+ cell counts but not with higher plasma viral load, clinical stage or sociodemographic variables.

Adolescent↗

The predictive value of changes in serologic and cell markers of HIV activity for subsequent clinical outcome in patients with asymptomatic HIV disease treated with zidovudine.

OBJECTIVE: To determine if serologic marker responses to zidovudine treatment during the first year of antiretroviral therapy could predict subsequent HIV disease progression independently of absolute CD4 lymphocyte responses. METHODS: We conducted a case-control study in patients with asymptomatic HIV disease, who were initiating zidovudine therapy in a randomized, prospective trial. A total of 102 patients who progressed to AIDS or advanced AIDS-related complex and 177 randomly selected controls matched by baseline CD4 cell count and duration of follow-up had serum samples (from prior to and at 8, 16, 32 and 48 weeks of zidovudine treatment) assayed for acid-disassociated HIV p24 antigen, beta 2-microglobulin (beta 2M), neopterin, soluble interleukin (IL)-2 receptor, soluble CD4 protein and soluble CD8 protein. RESULTS: Median time to event for cases was 20.2 months; median follow-up on study was 35.4 months for controls. After controlling for absolute CD4 count at baseline, increased baseline serum concentrations of HIV p24 antigen, beta 2M, neopterin, and soluble IL-2 receptor were highly predictive of increased risk of HIV disease progression. In a multiple logistic regression model, controlling for baseline marker values, change in beta 2M consistently added independent value to change in CD4 count in predicting subsequent risk of disease progression. CONCLUSIONS: Monitoring serum immunologic markers, in particular beta 2M, in addition to absolute CD4 lymphocyte counts prior to and within the first 4 months after initiating dideoxynucleoside therapy can increase the accuracy of estimations of subsequent long-term risk of clinical HIV disease progression. This information may be useful to clinicians and patients who are making decisions about initiating or changing antiretroviral therapy.

AIDS-Related Complex↗

[Idiopathic CD4 lymphocytopenia].

In healthy adults the CD4+ lymphocyte count in circulating blood is remarkably stable over a prolonged period. In patients infected with the human immunodeficiency virus (HIV) CD4 counts drop off sharply and can be used as a predictive marker of midterm outcome. However certain case reports of patients with out HIV infection, some reported as early as 1983, have led to a much publicized search for another immunosuppressive retrovirus. In reality no evidence of any such virus has been found and the Centers for Disease Control and the World Health Organisation have now defined the syndrome of idiopathic CD4 lymphocytopenia which includes a CD4 count below 300/mm3 or less than 20% of total lymphocytes in at least two successive counts without anti-HIV antibodies and without a known cause of immune deficiency or immunosuppressor treatment. The syndrome is extremely rare and although only recently identified, is probably not new. No endemic zone is known and there is no evidence of inter-human transmission. The clinical presentation is different from HIV infection. Although patients are susceptible to opportunistic infections, CD4 counts have relative stability and no hypergammaglobulinaemia occurs. Idiopathic CD4 lymphopenia is probably a primary immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗

Clinical, virologic, and immunologic response to efavirenz-or protease inhibitor-based highly active antiretroviral therapy in a cohort of antiretroviral-naive patients with advanced HIV infection (EfaVIP 2 study).

OBJECTIVE: To compare the clinical, immunologic, and virologic outcomes of efavirenz (EFV)-based versus protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) in severely immunosuppressed HIV-1-infected patients. DESIGN: Retrospective observational cohort study. METHODS: Responses were analyzed according to the intent-to-treat principle among antiretroviral-naive patients with < 100 CD4 cells/muL who started EFV (n = 92) or a PI (n = 218) plus 2 nucleoside reverse transcriptase inhibitors. The primary end point was time to treatment failure. Secondary end points were percentage of patients with a viral load < 400 copies/mL, time to virologic failure, time to CD4 lymphocyte count > 200 cells/microL, and incidence of opportunistic events or death. RESULTS: The median baseline CD4 cell count and viral load were 34 cells/microL and 5.54 log10 copies/mL (EFV group) and 38 cells/microL and 5.40 log10 copies/mL (PI group). Time to treatment failure was shorter with a PI-based regimen than with an EFV-based regimen (adjusted relative hazard [RH] = 2.19, 95% confidence interval [CI]: 1.23-3.89). After 12 months of therapy, a significantly higher proportion of patients receiving EFV reached a viral load < 400 copies/mL (69.4 vs. 45.1%; P < 0.05). The probability of virologic failure was higher with a PI than with EFV (adjusted HR = 2.52, 95% CI: 1.14-5.61; P = 0.024). There was no difference in time to CD4 cell count > 200 cells/microL or in incidence of opportunistic events or death. CONCLUSION: : In severely immunosuppressed, antiretroviral-naive, HIV-1-infected patients, treatment with an EFV-based regimen compared with a nonboosted PI-based regimen resulted in a superior virologic response with no difference in immunologic or clinical effectiveness.

Adult↗

[Correlation between CD4 lymphocytes and viral load in patients with HIV and tuberculosis].

OBJECTIVE: A retrospective study of the correlation between CD4 lymphocytes and the viral load in 16 HIV-patients with tuberculosis. MATERIAL AND METHODS: The clinical forms of presentation of tuberculosis were classified according to the location/s of the disease into: pulmonary, distinguishing between typical pulmonary and atypical according to the radiological pattern; extrapulmonary; mixed forms: pulmonary and extrapulmonary; and miliary tuberculosis. RESULTS: Tuberculosis was exclusively pulmonary in 7 cases (44%), all were atypical; extrapulmonary 6 (38%); mixed 2 (12%); and miliary 1 (6%). The mean CD4 lymphocyte count was 111.1 (range 5-360), in 11 (69%) the counts were below 200 cells/mm3. The lowest CD4 count was in the mixed forms with a mean of 45 cells/mm3 whilst the highest was obtained in pulmonary forms with a mean of 128.3 cells/mm3. The mean viral load was 4.82 log (range, 0-5.93), the highest load was for mixed forms with a mean 5.69 log, whereas the lowest load was for pulmonary forms with a mean of 4.19 log. No significant correlation was observed between CD4 lymphocytes and viral load (correlation coefficient--0.1163). CONCLUSIONS: Though no significant correlation was observed, a high CD4 was associated to a low viral load and inversely a low CD4 with a high viral load.

AIDS-Related Opportunistic Infections↗

Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy.

Data from 1330 human immunodeficiency virus type 1 (HIV-1)-infected patients enrolled in seven antiretroviral treatment trials were analyzed to characterize the clinical benefit of treatment-mediated reductions in plasma HIV-1 RNA levels. The risk of a new AIDS-defining event or death was reduced proportionally to the magnitude of the reduction of the HIV-1 RNA level during the first 6 months of therapy. Pretherapy HIV-1 RNA levels were prognostic independently of on-therapy levels. In addition, the reduction in risk associated with any given reduction of the level of HIV-1 RNA did not vary by pretherapy level. Having either a reduction in HIV-1 RNA level or an increase in CD4+ lymphocyte count, or both, was associated with a delay in clinical disease progression. This indicates that patient prognosis should be assessed using both HIV-1 RNA and CD4+ lymphocyte responses to therapy.

Acquired Immunodeficiency Syndrome↗

Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1-infected women in Dar es Salaam, Tanzania.

The objective of this study was to analyze the mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load at enrollment (36 weeks of gestation) in a cohort of HIV-1-seropositive breast-feeding women at the Dar es Salaam site of the multicenter Petra trial (a mother-to-child HIV-1 transmission intervention trial using antiretroviral therapy). Antiretroviral treatment was not available in this setting apart from the short treatment given within the trial around delivery to prevent mother-to-child transmission of HIV. T-lymphocyte subsets were determined by flow cytometry. Plasma HIV-1 RNA was quantified by the Amplicor HIV-1 RNA Monitor v 1.5 assay. Mortality after delivery was analyzed using the life-table technique and Cox regression. The analysis included 266 mothers. The CD4 cell counts at enrollment were <200 cells/mm in 14.5% of the mothers. The viral load at enrollment was >100,000 RNA copies/mL in 33.6% of the mothers. The mortality 24 months after delivery was 6.7% (95% CI = 3.1-10.1%). The mortality 24 months after delivery was 29.9% (95% CI = 13.1-46.9%) for mothers with <200 CD4 cells/mm at enrollment, 3.3% (95% CI = 0-6.6%) for mothers with 200-499 CD4 cells/mm, 2.9% (95% CI = 0-7.1%) for mothers with >500 CD4 cells/mm (P = 0.0000), 15.0% (95% CI = 6.6-23.4%) for mothers with viral load >100,000 copies/mL at enrollment, and 2.8% (95% CI = 0-5.6%) for mothers with viral load <100,000 copies/mL (P = 0.0000). In the multivariate analysis CD4 cell counts and viral load were both independent risk factors for mortality (P < 0.001 and P = 0.004, respectively). In conclusion, the mortality was high among women with severe immunosuppression or high viral load at enrollment, but not in the rest of the women. CD4 lymphocyte count in late pregnancy was a better predictor of death within 2 years than was viral load. The results support the World Health Organization recommendation to initiate antiretroviral treatment in resource-limited settings in HIV-1-infected adults with CD4 cell counts <200/mm and show that this is appropriate also among perinatal women.

Acquired Immunodeficiency Syndrome↗

Net benefits of resistance testing directed therapy compared with standard of care in HIV-infected patients with virological failure: A meta-analysis.

BACKGROUND: We incorporated the latest available information to evaluate the net benefit of using resistance testing in HIV-infected patients with virological failure. METHODS: Meta-analysis of randomized controlled trials comparing the clinical impact of selecting antiretroviral therapy according to results of resistance testing (phenotype or genotype) or according to the standard of care. The population studied included HIV-infected patients with virological failure. The outcome measures were the proportion of patients with HIV-RNA below the detection limit, and the decline in HIV-RNA and increase in CD4 lymphocyte count at the end of follow-up (< or = 24 weeks). Clinical trials were identified through searches in MEDLINE, EMBASE and proceedings from major infectious diseases meetings. RESULTS: Eight trials including a total of 1810 patients were eligible. Therapy guided by resistance testing resulted in a higher percentage of patients with HIV-1 RNA below the detection limit at the end of follow-up (< or = 24 weeks) as compared with the standard of care (40.2% vs. 32.9%). The pooled risk ratio was 1.23; 95% CI 1.09-1.40, p = 0.0009; test for heterogeneity I(2)=0%; p = 0.46). The number needed to treat [NNT] was 13 (95% CI: 9-25). Subgroup analysis showed greater benefits in therapy guided by genotype testing with expert interpretation, when compared with standard of care (NNT: 5; 95% CI: 3-9; p = 0.06). The heterogeneity among trials for evaluating HIV-1 RNA decline and CD4 lymphocyte cell count increase made unfeasible pooling the results across studies. CONCLUSION: Genotype testing with expert interpretation showed the greatest benefit for guiding therapy in patients with HIV infection and virological failure.

Anti-HIV Agents↗

[Prevention of wasting and opportunistic infections in HIV-infected patients in West Africa: a realistic and necessary strategy before antiretroviral treatment].

The medical inequalities between countries of the North and South (infrastructure, drug availability, medical techniques) are particularly marked in terms of the challenge posed by HIV infection. We propose a strategy for monitoring adult patients in West Africa that is appropriate to the situation in the field and to economic constraints. The aim of this strategy is to increase the quality of life and the life expectancy of HIV-infected adults and to prevent the overcrowding of hospital departments with patients in the terminal phase of AIDS. We analyzed the biological and clinical spectrum of HIV infection before the onset of the diseases that define AIDS (excluding pulmonary tuberculosis). We found that it was particularly important to diagnose B-stage diseases early, especially atypical chronic cutaneous and mucous diseases. Careful analysis of data from a routine hemogram (total lymphocyte count 2500/ml; paradoxical eosinopenia), even in the absence of a CD4 lymphocyte count, should also enable clinicians from a wide variety of health structures to identify the HIV-infected patients most likely to benefit from more detailed clinical follow up, prophylaxis of opportunistic infections using cotrimoxazole, nutritional checkups and prevention of wasting. Cachexia is the most common AIDS-associated disease in West African patients. It involves an overall decrease in calorific intake, diarrhea, immune system activation, an increase in TNFalpha production and greater energy expenditure when resting. Recent nutritional studies have shown that it is vital to optimize the calorific intake of HIV-infected patients presenting with chronic diarrhea, before the onset of severe immune deficiency, to prevent wasting. So, spontaneous calorific intake should de routinely determined in HIV-infected patients and an optimal diet provided. Specific training in nutrition is required for doctors and nurses, as is consideration of the logistic organization required to provide nutritional support to HIV-infected adults. Despite the large number of individuals infected and the lack of sophisticated paraclinical facilities, we feel that it is possible to establish rational management "a minima" of HIV infection in West Africa, whilst waiting for antiretroviral drugs to become more widely available. This strategy could be of direct benefit to patients without swallowing up the financial resources of the health system in expensive biological follow up. Such basic management is also required before the new antiretroviral drugs become widely available. Research should be carried out in parallel in several reference centers in West Africa to determine the most effective associations of antiretroviral drugs and the optimal timing of treatment during the course of infection and to assess the potential side effects of these drugs in HIV patients exposed to recurrent antigenic stimulation by a wide diversity of pathogens.

AIDS-Related Opportunistic Infections↗

Change from dual- to single-platform reporting of CD4/CD8 values: experience from a small district general hospital laboratory.

Accurate and reliable CD4 and CD8 counts are essential for monitoring HIV disease progression or successful therapy. CD4 and CD8 counts can be determined on a flow cytometer by either single- or dual-platform technology. Dual-platform technology uses a haematology analyser to obtain a total white cell count and lymphocyte absolute count. CD4 and CD8 absolute values are then calculated from the CD4 and CD8 percentage positive results obtained from the flow cytometer. Single-platform technology uses latex beads of a predefined concentration, which are added to the blood sample immediately before flow cytometric analysis, thereby removing the need to use an additional analyser. Recent recommendations propose that single-platform technology should be the gold standard for CD4 measurement because it offers better inter-laboratory coefficients of variation (CVs). Before changing to single-platform technology in our department, CD4 and CD8 absolute counts, determined on 20 healthy volunteers, were used to establish new normal ranges for single-platform technology (Coulter epics XL), permitting absolute value data for dual-platform and single-platform technologies to be compared. Data obtained with single-platform technology was significantly higher for both CD4 and CD8 (P=0.001 and P=0.003, respectively). For CD4, mean single-platform value was 0.993 x 10(9)/L (+SD = 0.510-1.376) and dual-platform value was 0.920 x 10(9)/L (+SD = 0.500-1.340). For CD8, single-platform value was 0.483 x 10(9)/L, (+SD = 0.207-0.756) and dual-platform value was 0.457 x 10(9)/L (+SD = 0.222-0.692). Thus, the differences between dual- and single-platform absolute CD4 and CD8 results were small (8% and 6%, respectively) but significant. It is important, therefore, that clinicians closely monitoring CD4 and CD8 values and are informed of any laboratory changes.

CD4 Lymphocyte Count↗