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Cryptococcosis in HIV infection of man: an epidemiological and immunological indicator?

Cryptococcosis is an epidemiological and immunological indicator due to the absence of Cryptococcus neoformans as a saprophyte in immunocompetent humans and the advantage of specific C. neoformans culture. On this basis, a report is presented on the CD4 lymphocyte count of 36 AIDS patients suffering from cryptococcosis and other concomitant or missing opportunistic AIDS-defining infections. In 26 out of 36 patients, i.e. 72%, a CD4 lymphocyte count of < or = 50/microL (mean value 39.5%) was found. Cryptococcosis as the sole opportunistic infection was diagnosed in 5 cases (13.9%). In 31 cases, various combinations of AIDS-associated diseases were found: Pneumocystis carinii pneumonia (PCP) (n = 19), cytomegalovirus infection (CMV) (n = 10), Kaposi's sarcoma (n = 6), Mycobacterium avium intracellulare infection (MAI) (n = 5), pneumonia (n = 2), toxoplasmosis (n = 2), Candida esophagitis (n = 1), tuberculosis (n = 1), lambliasis (n = 1), salmonellosis (n = 1) and wasting syndrome (n = 5). The conspicuous simultaneous occurrence or succession of pneumocystosis and cryptococcosis and the contrasting absence of aspergillosis and mucormycosis (zygomycosis) are commented. Based on the present observations in HIV-infected persons in Berlin, a CD4 lymphocyte count of < 150/microL may be used as a parameter indicating a predisposition for cryptococcosis as an airborne AIDS-defining infection. Attention is drawn to bird droppings as the sole habitat of C. neoformans and accidental niche of various other microorganisms.

AIDS-Related Opportunistic Infections↗

Prevalence of microsporidiosis due to Enterocytozoon bieneusi and Encephalitozoon (Septata) intestinalis among patients with AIDS-related diarrhea: determination by polymerase chain reaction to the microsporidian small-subunit rRNA gene.

Microsporidia are emerging as opportunistic pathogens in patients with AIDS. Enterocytozoon bieneusi and Encephalitozoon (Septata) intestinalis have been implicated in enteric infections in AIDS patients with chronic diarrhea, a wasting syndrome, and malabsorption. We used the polymerase chain reaction (PCR) and primers that amplify the conserved regions of the small-subunit rRNA (SSU-rRNA) gene of E. bieneusi and E. intestinalis in tissue specimens from HIV-infected patients with and without diarrhea to examine the association between microsporidia and diarrhea in patients with AIDS. Tissue specimens were obtained from 68 patients with AIDS and diarrhea (mean CD4 lymphocyte count, 21/mm3) and 43 AIDS patients without diarrhea (mean CD4 lymphocyte count, 60/mm3). By means of PCR with use of the SSU-rRNA primers specific for E. bieneusi and E. intestinalis, we found that 44% of patients with diarrhea were infected with microsporidia, whereas only 2.3% of the patients without diarrhea were infected with microsporidia (P < .001). There was a clear association between the presence of microsporidia and diarrhea. In addition, the SSU-rRNA primers proved to be sensitive and specific when used in this clinical setting.

AIDS-Related Opportunistic Infections↗

[Survival in HIV infection and AIDS].

Duration of the AIDS-free period after HIV-infection and survival time vary to a wide extent. About 50 percent of the patients develop AIDS within 10 years. The most important prognostic factor is the CD4-lymphocyte count. The risk of AIDS increases significantly after CD4-lymphocyte counts drop below 400/microliters. Another prognostic factor is age. In older patients disease progresses more rapidly. AIDS often is preceded by an AIDS-Related-Complex characterized for example by Oral Candidiasis, Hairy Leukoplakia or Zoster of more than one dermatome. AIDS mostly develops 1/2 to 1 year after AIDS-Related-Complex. After AIDS is diagnosed the median survival time is not longer than 1 1/2 years. Single patients live much longer. Prognosis is influenced by the disease defining AIDS. Kaposi's Sarcoma often occurs early in the course of immunodeficiency and median survival is longer than after other opportunistic diseases. Survival also is longer after Pneumocystis Carinii Pneumonia since it is well treatable. A very short survival has been noticed after Non-Hodgkin-Lymphoma. During the last few years survival after HIV-infection and AIDS has been prolonged a little by sufficient prophylaxis of Pneumocystis Carinii Pneumonia which is the most frequent opportunistic disease, by antiretroviral treatment with Zidovudine and by increase of knowledge which makes early diagnosis and treatment of opportunistic diseases possible.

Acquired Immunodeficiency Syndrome↗

A pilot trial of indinavir, ritonavir, didanosine, and lamivudine in a once-daily four-drug regimen for HIV infection.

OBJECTIVE: To evaluate the tolerance, pharmacokinetics, and virologic and immunologic outcomes of once-daily indinavir, ritonavir, didanosine, and lamivudine in HIV-seropositive individuals. DESIGN: Open-label 24-week pilot study. PATIENTS: Ten HIV-seropositive subjects who were either antiretroviral-naive or minimally experienced with short-term single-or dual-nucleoside therapy provided informed consent and were enrolled. All subjects received didanosine (400 mg) 30 to 60 minutes before a meal followed by indinavir (1200 mg), ritonavir (400 mg), and lamivudine (300 mg) concurrent with the aforementioned meal. METHODS: Safety laboratory tests, including a complete blood cell count and amylase, lipase, liver transaminase, and nonfasting lipid monitoring as well as plasma HIV viral load and CD4+ lymphocyte count, were carried out at monthly intervals. Genotyping was performed at baseline. Pharmacokinetic studies for indinavir and ritonavir were performed at week 8. RESULTS: Nine of 10 subjects completed 24 weeks of therapy. No subject demonstrated primary protease inhibitor mutations at baseline. Toxicities experienced by subjects were typically mild and consistent with those commonly reported for each of the medications, including two cases of hematuria. By week 24, median nonfasting cholesterol and triglyceride levels increased by 49% and 108%, respectively. Median baseline plasma HIV viral load and CD4+ lymphocyte count were 29,292 (4.47 log10) copies/ml and 224 cells/mm3, respectively. Eight of 10 subjects had a plasma HIV viral load of <50 copies/ml by week 12. The 2 subjects with a detectable HIV viral load reached <50 copies/ml by week 28. Median CD4+ lymphocyte counts increased by 193 cells/mm3 at week 24. Indinavir and ritonavir plasma concentrations remained above respective inhibitory and effective concentrations (IC95 and EC50) (uncorrected for protein binding) throughout the 24-hour dosing interval for 6 of 10 and 8 of 10 subjects, respectively. CONCLUSIONS: Our pilot study demonstrates excellent virologic suppression despite low minimum protease inhibitor concentrations during a dosing interval in some patients and is supportive of further study.

Adult↗

Does European or non-European origin influence health care and prognosis for HIV patients in Europe? The EuroSIDA Study Group.

BACKGROUND: Previous studies, especially in North America, have shown that socio-economic factors may influence the prognosis for patients with HIV. This study was performed in order to determine if European or non-European origin influence provision of health-care and survival among HIV patients in Europe. METHODS: Fifty HIV clinics in 17 European countries are involved in a European prospective, observational multicentre study. In total, 7230 consecutive patients with HIV attending a routine clinic visit were included in the study. Data on demographics, treatment and laboratory results were collected at time of recruitment into the study and thereafter every 6 months. RESULTS: The median CD4+ lymphocyte count at AIDS diagnosis was 60/mm3, and was similar for all ethnic groups (P = 0.87, Kruskall-Wallis test). The median terminal CD4+ lymphocyte count was 17/mm3 and, again, there was no significant difference between continents of origin (P = 0.35, Kruskall-Wallis test). Antiretroviral drugs were initiated at similar median CD4+ lymphocyte counts and there was no statistically significant difference in survival after a diagnosis of AIDS. CONCLUSIONS: AIDS was diagnosed at the same level of immunodeficiency independent of European or non-European origin and antiretroviral drugs were provided at similar levels of immunodeficiency. No differences in survival depending on continent of origin was found. In spite of these encouraging findings concerns remain that belonging to an ethnic minority can be an obstacle in getting into contact with treatment facilities and thus benefiting from developments in the management of HIV.

Adult↗

Sequential occurrence of IgM, IgM/IgG, and gp120-IgM/IgG complement complexes on CD4+ lymphocytes in relation to CD4+ blood lymphocyte depletion in HIV+ hemophilia patients: results of a 10-year study.

The concept of autoimmune mechanisms playing an integral role in the pathogenesis of HIV disease is rapidly gaining ground. In this study, we determined IgM and IgG antibodies, complement fragments and gp120 on the surface of CD4+ lymphocytes using double-fluorescence flow cytometry. Sequential analysis demonstrated an inverse relationship of autoantibodies and CD4+ lymphocyte counts in the peripheral blood. HIV+ patients without autoantibodies (16/104 = 15%) had the highest CD4+ blood cell counts (324 +/- 264/microliters; mean +/- SD). CD4+ counts were successively lower in patients with complement-fixing IgM (243 +/- 240/microliter), complement-fixing IgG and IgM (139 +/- 138/microliter), or gp120-IgM/IgG complement complexes on the surface of CD4+ cells (38 +/- 45/microliter, P = 0.03). Individual patient profiles show that IgM autoantibodies typically are formed early after HIV infection and appear to deplete CD4+ lymphocytes very slowly, whereas complement-fixing IgG autoantibodies are generated at a later stage and deplete CD4+ lymphocytes more efficiently. The presence of both soluble gp120 and complement-fixing autoantibodies on CD4+ lymphocytes is associated with very low CD4+ cell counts and coincides with progression to terminal disease. Early during HIV infection autoantibody production is rather unstable, but it becomes more stable with disease progression and persists in advanced stages of the disease. These data suggest that autoantibody formation against CD4+ lymphocytes is a pathogenic mechanism for CD4+ cell depletion.

Antigen-Antibody Complex↗

[HIV infection: a case report].

A case is presented of HIV-infection in a child born to an HIV(+) mother belonging to a high-risk group. The diagnosis was determined through multiple identification of anti-HIV-antibodies by means of the ELISA and Western blot tests in a child with lymphopenia, depressed CD4 lymphocyte count and diminished CD4 and CD8 index. Retrovir, among others, has been used in treatment. At present the child is 3.5 years-old and is developing normally. Persistent insignificant enlargement of all groups of lymphnodes, the liver and the spleen is present Full-blown AIDS has not developed yet.

Blotting, Western↗

Initiation of highly active antiretroviral therapy at CD4+ T lymphocyte counts of >350 cells/mm3: disease progression, treatment durability, and drug toxicity.

We compared clinical disease progression in 159 human immunodeficiency virus (HIV)-infected persons for whom highly active antiretroviral therapy (HAART) was initiated when they had CD4(+) T lymphocyte counts of 350-499 cells/mm(3) with progression in 174 HIV-infected patients for whom it was not. Disease progression did not differ between the 2 groups (P=.21, log-rank test). Fifty-three percent of the 159 treated patients had HIV type 1 RNA levels of >400 copies/mL at the most recent evaluation, and 41% had experienced adverse drug reactions necessitating a change in regimen. These findings support the recommendation that HAART not be initiated for patients with CD4(+) cell counts of >350 cells/mm(3).

Adult↗

Nongenital dermatologic disease in HIV-infected women.

BACKGROUND: Dermatologic disease in HIV-infected women has not been adequately characterized. OBJECTIVE: The main purposes of this study were to characterize nongenital dermatologic disease in HIV-infected women and correlate these diagnoses with CD4 lymphocyte count to compare these findings with those in published reports of men. METHODS: This study was a retrospective chart review of female patients with dermatologic diagnoses followed up at an HIV clinic in New York City, seen by either a dermatologist (49 patients) and/or a primary care practitioner (114 patients). CD4 lymphocyte count was recorded if available within 6 months of diagnosis; mean CD4 count was calculated for all disorders with 5 or more diagnoses. RESULTS: Oropharyngeal candidiasis, drug eruption, dermatophytosis, rash (not otherwise specified), nongenital herpes simplex, herpes zoster, and seborrheic dermatitis were the most prevalent diagnoses made by primary care providers. Itchy red bump disease, acne, atopic dermatitis, xerosis, seborrheic dermatitis, nongenital warts, and molluscum contagiosum were the most prevalent diagnoses made by the dermatologist. Mean CD4 lymphocyte count was lowest in itchy red bump disease, nongenital warts, nongenital herpes simplex, xerosis, and drug eruptions. CONCLUSION: There appears to be no appreciable difference in the spectrum or prevalence of dermatologic disease in HIV-infected women versus HIV-infected men, except for a lower prevalence of Kaposi's sarcoma, oral hairy leukoplakia, and possibly onychomycosis in women. The degree of immunosuppression associated with various dermatoses in HIV-infected women is similar to that in men, except perhaps for molluscum contagiosum, which may appear earlier in women.

Adult↗

Treatment of advanced Kaposi's sarcoma using a combination of bleomycin and vincristine.

Eighteen patients with disseminated AIDS-related Kaposi's sarcoma (KS) and compromised bone marrow function were treated with a relatively non-myelosuppressive regimen of bleomycin and vincristine (BV). At study entry, the patients presented with the following median laboratory values: hemoglobin of 9.5 g/dl, granulocyte counts of 1,173/mm3, platelet counts of 218,000/mm3, and CD4 lymphocyte counts of 58/mm3. All patients had extensive Kaposi's sarcoma. Nine patients had visceral involvement: four with pulmonary involvement, two with gastrointestinal involvement, and three with both. Following a median number of seven cycles of biweekly chemotherapy, complete or partial tumor responses were achieved in 13 patients (72%). Two patients experienced bleomycin-induced skin toxicities, whereas 10 others (55%) experienced peripheral sensory neuropathy requiring vincristine dose reductions. Opportunistic infections had occurred in 11 patients prior to initiation of chemotherapy and in 16 after initiation of chemotherapy. Despite the frequent development of opportunistic infections, BV chemotherapy was relatively well tolerated and resulted in a high response rate in this patient population that presented with suboptimal marrow function and extremely low CD4 lymphocyte counts.

Acquired Immunodeficiency Syndrome↗

Depressive symptoms and CD4 lymphocyte decline among HIV-infected men.

OBJECTIVE: To investigate whether high levels of depressive symptomatology at baseline predict more rapid decline of CD4 lymphocyte counts and progression of clinical disease in persons infected with the human immunodeficiency virus (HIV). DESIGN: Prospective cohort study with semiannual data collection waves and up to 66 months of follow-up. SETTING: Population-based probability sample of single men in areas of San Francisco with high case rates of the acquired immunodeficiency syndrome (AIDS). SUBJECTS: All 330 homosexual or bisexual men who by January 1985 had serological evidence of HIV infection but had not had an AIDS diagnosis. Analysis of CD4 lymphocyte change was performed for 277 subjects (83.9%) who had three or more CD4 lymphocyte counts recorded during the study period January 1985 through July 1990. OUTCOME MEASURES: Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression scale (CES-D). All subjects were classified according to two indicators of depression: (1) as overall depressed using a cut point of 16 or higher on the complete CES-D, and (2) as affectively depressed using a cut point of more than 1 SD above the mean on a subscale of the CES-D measuring affective depression. Laboratory and symptom measures, antiretroviral use, demographics, and behavioral measures were also used. The primary outcome measure was the rate of change of the CD4 lymphocyte count. Secondary outcomes were AIDS-free survival and mortality. RESULTS: At baseline 65 subjects (19.7%) were classified as depressed on the overall scale and 53 (16.1%) were classified as depressed on the affective scale. The unadjusted mean rate of CD4 change was 38% greater for overall depressed subjects than for the overall nondepressed (-0.0812 vs -0.0588 x 10(9)/L [-81.2 vs -58.8/microL per year; P = .07) and 34% greater for affectively depressed subjects than for the affectively nondepressed (-0.0804 vs -0.0598 x 10(9)/L per year; P = .06). In hierarchical multivariate analysis controlling for antiretroviral use, symptoms, and other predictors, baseline overall depression was associated with an excess decline in CD4 count of -0.0285 x 10(9)/L per year (95% confidence interval, -0.0496 to -0.0073), and baseline affective depression was associated with an excess decline in CD4 count of -0.0236 x 10(9)/L per year (95% confidence interval, -0.0464 to -0.0008). Neither overall depression nor affective depression was significantly associated with earlier AIDS diagnosis or earlier mortality. CONCLUSIONS: Overall depression and affective depression predicted a more rapid decline in CD4 lymphocyte counts; this association was not attributable to baseline physiological differences. While the mechanism of the association remains unknown and cannot be addressed directly by this study, the data suggest that it can be explained neither as simply a reflection of perceived somatic symptoms nor as the result of differences in recreational drug and alcohol use. Further study is necessary to determine whether treating depression can alter the course of HIV infection.

Adult↗

Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus: clinical characteristics in a case-control study.

Clinical characteristics associated with bacillary angiomatosis and bacillary peliosis (BAP) in patients with human immunodeficiency virus (HIV) infection were evaluated in a case-control study; 42 case-patients and 84 controls were matched by clinical care institution. Case-patients presented with fever (temperature, > 37.8 degrees C; 93%), a median CD4 lymphocyte count of 21/mm3, cutaneous or subcutaneous vascular lesions (55%), lymphadenopathy (21%), and/or abdominal symptoms (24%). Many case-patients experienced long delays between medical evaluation and diagnosis of BAP (median, 4 weeks; range, 1 day to 24 months). Case-patients were more likely than controls to have fever, lymphadenopathy, hepatomegaly, splenomegaly, a low CD4 lymphocyte count, anemia, or an elevated serum level of alkaline phosphatase (AP) (P < .001). In multivariate analysis, a CD4 lymphocyte count of < 200/mm3 (matched odds ratio [OR], 9.9; P < .09), anemia reflected by a hematocrit value of < 0.36 (OR, 19.7; P < .04), and an elevated AP level of > or = 2.6 mukat/L (OR, 23.9; P < .05) remained associated with disease after therapy with zidovudine was controlled for. BAP should be considered an AIDS-defining opportunistic infection and should be included in the differential diagnosis for febrile, HIV-infected patients with cutaneous or osteolytic lesions, lymphadenopathy, abdominal symptoms, anemia, or an elevated serum level of AP.

AIDS-Related Opportunistic Infections↗

[Anterior uveitis and cidofovir].

PURPOSE: This retrospective study was designed to determine the different parameters involved in the occurrence of uveitis during treatment with codofovir. PATIENTS AND METHODS: This study included 10 patients out of 13 treated with cidofovir for cytomegalovirus (CMV) disease. Ocular examination, CD4+ lymphocyte count, and creatinine clearance were performed for each case of uveitis. RESULTS: During the 17-month study, 20 uveitis cases were analyzed. The first attack occurred after a median interval of 7.6 doses. At the time of ocular inflammation, 65% of the cases had a CD4+ lymphocyte count >=100x10(6)/L, the patients thus had an improved immune function. Half of the patients had a normal creatinine clearance. The patients with a CD4+ lymphocyte count<100x10(6)/L who presented one or more incidents of uveitis had an abnormal clearance, thus probably inducing intraocular storage of the drug. CONCLUSION: The occurrence of anterior uveitis during treatment with cidofovir is induced by the association of several parameters: a previous history of CMV retinitis, improvement of the immune function state, and intraocular storage of the drug.

AIDS-Related Opportunistic Infections↗

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine.

OBJECTIVE: To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. DESIGN: Retrospective study of changes in laboratory markers and survival. SETTING: Multicentre trial at university hospital clinics. SUBJECTS: 90 Patients with AIDS or AIDS related complex. INTERVENTION: Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. MAIN OUTCOME MEASURES: Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, beta 2 microglobulin, and neopterin; survival of the patient. RESULTS: The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (v AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum beta 2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. CONCLUSION: These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

AIDS-Related Complex↗

[Simplified CD4+ T-lymphocyte count in patients with HIV/AIDS in Mexico].

OBJECTIVE: To study the correlation between ALC and CD4 cell counts and to find alternative ways of counting CD4+ T-lymphocytes. MATERIAL AND METHODS: The double positivity for CD3/CD4 antibodies was measured in 175 consecutive HIV-positive patients using flow cytometry; in these cases a difference was made between counting cells that were positive for both antibodies vs those that were positive only to CD4. ALC and CD4 counts were also compared among 500 subjects infected with HIV, using linear regression analysis and comparing the number of dissimilar cases for counts below 200 cells/microliters and ALC counts lower than 1 500 and 2000 cells/microliters. RESULTS: In the 175 cases measured by the CD3/CD4 antibody combination the mean percent was 13.8% and for total CD4 cells 14.2% (p = NS); the mean difference was 0.4% and the median 0.2%. For the 500 patients the mean ALC was 1 700 cells/microliters and the mean CD4 count was 219 cells/microliters; the correlation coefficient was 0.59. CONCLUSIONS: These data suggest a poor correlation of ALC and CD4 cell counts, thus it is impossible to predict CD4 on the basis of ALC. This is the reason why it is necessary to measure CD4 cells separately. The difference between measuring double positive CD3/CD4 cells vs only CD4 positive cells was not significant. Our data suggest that the use of a single CD4 antibody may cut costs and still produce clinically useful information.

Acquired Immunodeficiency Syndrome↗

[Studies on relationship between immunodeficiency in HIV-infected people and condition of upper gastrointestinal tract mucosa, prevalence of mycosis and Helicobacter pylori infection].

HIV infection leads to progressive deterioration of immunity. Upper gastrointestinal symptoms are often reported in patients with this infection. The aim of the study was to evaluate morphological changes in upper gastrointestinal tract mucosa and prevalence of opportunistic infections and Helicobacter pylori in HIV-infected people in relationship to the degree of immunosupression. We studied 94 HIV-infected patients with dyspeptic symptoms, 47 suffered from severe immunodeficiency expressed by low CD4+ lymphocyte count below 200/ mm3. Control group consisted of 52 non HIV-infected patients. During endoscopy, gastrointestinal tract mucosa was evaluated and biopsy samples were taken from gastric body and antrum for histopathological analysis and rapid urease test. In patients with CD4+ lymphocyte count below 200/mm3, endoscopic examination revealed significantly more frequent esophageal candidiasis (36%); whereas reflux esophagitis (13%) was significantly less often diagnosed in comparison to the rest of the patients. Duodenitis and duodenal erosions were also less frequent in them. Prevalence of Helicobacter pylori infection in gastric antrum was significantly lower in HIV-infected patients with severe immunodeficiency (40%) in comparison to the rest of the patients (72%) and control group (69%). Chronic active gastritis of the antral mucosa was less frequent in HIV-infected patients with CD4+ lymphocyte count below 200/mm3.

AIDS-Related Opportunistic Infections↗

The management of musculoskeletal infection in HIV carriers.

Over a three-year period, the authors prospectively implemented a protocol for management of musculoskeletal sepsis (MSS) in HIV carriers in Yaounde, Cameroon. The diagnosis of MSS was based on conventional criteria. HIV carriage was screened by an ELISA test and confirmed with the Western Blot technique. The immune status was based on CD4 lymphocyte count by flow cytometry; patients were classified as non-immunodepressed (NID), mildly immunodepressed (MID), or severely immunodepressed (SID) based on their CD4 lymphocyte count, as the latter was respectively over 500, between 200 and 500 or less than 200 per ml. Infection was treated by surgical debridement followed by a long-course targeted antibiotic therapy. All SID patients and some MID patients with AIDS-related symptoms also had standard antiretroviral (ARV) therapy. Thirty-one of 294 patients seen with musculoskeletal sepsis during the study period and tested for HIV were found to be HIV carriers. Their mean age was 33 years; the male/female ratio was 1.58. The following clinical pictures were observed: chronic osteomyelitis (COM) in 32.3% of the cases, septic arthritis (SA) in 38.7%, soft tissue infection (STI) in 25.8%; the last case was a severe leg complication of Buruli Ulcer (BU). Among these 31 patients, 38.7% were classified as SID (5 COM, 4 SA, 2 STI and the BU patient), 25.8% as MID (2 COM, 4 SA, 2 STI) and 35.5% as NID (3 COM, 6 SA, 2 STI). The organisms involved were not specific. Fifteen patients were managed conventionally, while the other 16 had the usual treatment associated with ARV therapy. The immediate outcome of MSS was good in 29 patients, after a mean hospital stay of five weeks; in two cases of septic arthritis of the knee, a second debridement was needed, due to persistent drainage, and the sinuses all closed. Three months after discharge, one patient with COM of the humerus developed a low-flow fistula which was closed after a revision sequestrectomy. After one year, none of the patients complained of any symptom suggesting reactivation of their MSS. There is no evidence that HIV carriage is in itself a high risk factor for musculoskeletal sepsis; the incidence of HIV carriage was indeed virtually similar in the 294 patients with MSS and in the general population, i.e. around 10%. However, in order to improve the outcome following musculoskeletal infections in patients with HIV, their management should take into account their immune status, based on a CD4 lymphocyte count. NID patients should be treated as any other patients with MSS, while SID should have additional standard ARV treatment. For those who are MID, the indication for antiretroviral therapy should depend on the presence of one or more AIDS-related signs.

Adolescent↗

Immunodeficiency and the risk of death in HIV infection.

OBJECTIVE: To describe the rate of development of immunodeficiency in human immunodeficiency virus (HIV) infection and to relate this to the risk of death. DESIGN: Inception cohort followed up for up to 12 years from HIV seroconversion until January 1, 1992. SETTING: A regional hemophilia center based in a major teaching hospital. PATIENTS: All 111 patients with hemophilia who seroconverted to HIV-1 between 1979 and 1985 were registered at the center. Patients have been closely followed up clinically and immunologically. OUTCOME MEASURES: Development of immunodeficiency, defined by a CD4 lymphocyte count falling beneath 0.20 and 0.05 x 10(9)/L, and death. RESULTS: Kaplan-Meier estimates suggest that almost half (46%; 95% confidence interval [CI], 26% to 66%) of patients alive 12 years after seroconversion will have a CD4 lymphocyte count that has remained above 0.05 x 10(9)/L. Thirty-five percent (95% CI, 22% to 48%) remain above 0.20 x 10(9)/L. Thirty-seven patients died of HIV-related causes, and there was a 52% probability (95% CI, 35% to 69%) of HIV-related mortality by 12 years from seroconversion. Mortality risk was closely associated with severe immunodeficiency. There was only a 15% chance (95% CI, 6% to 25%) of HIV-related death occurring before a CD4 count of below 0.05 x 10(9)/L had been reached. There was an average of one HIV-related death per 96.7 patient-years of observation before the CD4 count had fallen below 0.05 x 10(9)/L, as compared with one death per 2.5 patient-years of observation after the CD4 count had fallen below this level (P < .0001). CONCLUSIONS: In patients with HIV infection who are closely followed up, the risk of death is low before the CD4 lymphocyte count has fallen to 0.05 x 10(9)/L, a count many patients remain above up to 12 years after seroconversion.

CD4-Positive T-Lymphocytes↗