Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.

In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to an active T cell suicide process, apoptosis, which is involved in the selection of the T cell repertoire. We have proposed that inappropriate induction of such a cell death program in the mature CD4+ T cell population could account for both early qualitative and late quantitative CD4+ T lymphocyte defects of human immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron. 1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T cell death process, with the biochemical and ultrastructural features of apoptosis. Activation-induced cell death occurred only in the CD4+ T cell population from HIV-infected asymptomatic individuals and was not observed in T cells from any of 58 HIV-seronegative controls, including nine patients with other acute or chronic infectious diseases. Activation-induced CD4+ T cell death was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell proliferation to stimuli, including PWM, superantigens, and the tetanus and influenza recall antigens. These findings may have implications for the understanding of the pathogenesis of acquired immune deficiency syndrome and for the design of specific therapeutic strategies.

ABCB1 allele polymorphism is associated with virological efficacy in naïve HIV-infected patients on HAART containing nonboosted PIs but not boosted PIs.

OBJECTIVE: To assess the effect of the multidrug resistance-1 single nucleotide polymorphism (ABCB1 SNP) C3435T in exon 26 on the virological responses to first-line protease inhibitor (PI)-containing HAART regimens. METHOD: A cohort of 182 HIV-infected patients with a PI-containing HAART regimen initiated from 1997 to 2004 was enrolled. Time to the first indetectable viral load (VL) was determined in patients with the CC, CT, or TT genotype. RESULTS: There were 37%, 44%, and 19% of patients who had the CC, CT and TT genotypes, respectively. The median estimated times to VL indetectability in the CC, CT, and TT groups were respectively 5.9, 3.9, and 4.8 months (p= .06). In patients on a non-boosted PI regimen, ABCB1 genotype was associated with time to VL indetectability that was shorter in patients with the CT than CC genotype (CT vs. CC, hazard ratio [HR]=0.62, p= .02; TT vs. CC, HR= 0.72, p= .21). This association was not found in patients with first-generation boosted PI-containing regimens and especially not with second-generation boosted PI-containing regimens. CONCLUSION: Our results show that the ABCB1 SNP in exon 26 is associated with virological efficacy in HIV-infected patients treated with non-boosted PI-containing regimens but not with those containing boosted PIs, particularly of the second generation.

[Primary Salmonella vascular graft infection and conservative treatment]. / Infection primaire de prothèse vasculaire à salmonelle et traitement conservateur.

The authors report an unusual case of prosthetic vascular graft infection due to Salmonellatyphimurium. The initial treatment combined antibiotherapy and surgical replacement of the arteriovenous graft. The infection relapsed within 6 weeks and was successfully treated with antibiotics only. Five cases of vascular graft infection due to Salmonella have been reported so far, but only one occurred in a previously healthy man and was not related to local infection, but to bacteremic seeding. Specific features of vascular graft infection and importance of prevention are discussed.

Incidence of and risk factors for severe liver toxicity in HIV-infected patients on anti-tuberculosis treatment.

OBJECTIVE: To assess the incidence and risk factors for severe liver toxicity in human immunodeficiency virus (HIV) infected patients on anti-tuberculosis treatment and the impact of patients' characteristics and concomitant medications instituted during the first week of antituberculosis treatment. METHODS: HIV-infected patients referred to six French hospitals between 1 January 1992 and 31 December 2004, with confirmed or 'presumptive' tuberculosis (TB). Liver toxicity was studied during the first 2 months of TB treatment. RESULTS: During the 12 years of the study period, 144 patients were enrolled. Severe liver toxicity developed in 15 (10.7%). The median time to development of liver toxicity was 14 days. In the univariate analysis, high baseline bilirubin levels (P = 0.004), CD4 cell counts between 50 and 100 cells/mm3 (P = 0.022) and the use of fluconazole (P = 0.0005) were associated with liver toxicity. In the multivariate analysis, independent risk factors were abnormal baseline alanine aminotransferase (ALT) (P = 0.028) and bilirubin levels (P = 0.033) and the use of fluconazole (P = 0.008). CONCLUSION: Severe liver toxicity is frequent, and occurs early in the course of anti-tuberculosis treatment. ALT and bilirubin levels should be closely monitored during the first month of treatment, especially in patients with high baseline ALT or bilirubin levels. We suggest caution when prescribing fluconazole and anti-tuberculosis drugs concomitantly, although this needs to be confirmed and further investigated.

Safety of prolonged high-dose levofloxacin therapy for bone infections.

The records of 84 patients with bone infections treated with high-dose levofloxacin (i.e. 0.75-1g daily) for more than 4 weeks were reviewed. Patients were given either 500 mg b.i.d. throughout the treatment period [Group 1 (n=41)], 500 mg b.i.d. for 3 weeks and then 750 mg q.d. [Group 2 (n=21)] or 750 mg q.d. for the whole treatment period [Group 3 (n=22)]. All patients had combined therapy, including levofloxacin-rifampin in 62 cases (73.8%), for an average duration of 13.7 weeks. Muscular pain and/or tendonitis were reported in 19 patients (22.6%) which affected more patients in Groups 1 and 2 than in Group 3 (14/41 and 5/21 vs. 0/22; p=0.01 and 0.001, respectively). A dosage of 750 mg q.d. may be warranted for prolonged high-dose levofloxacin treatment in patients with bone infections rather than 500 mg b.i.d. for the entire duration of treatment, or for the first 3 weeks.

Treatment of bone and joint infections caused by Gram-negative bacilli with a cefepime-fluoroquinolone combination.

A 3-year retrospective study evaluated the effectiveness and safety of cefepime plus a fluoroquinolone for treating bone and joint infections caused by Gram-negative bacilli (GNB) in 28 patients. Intra-operative cultures yielded primarily Pseudomonas spp. and Enterobacter cloacae. Full recovery (cure) was observed in 79% of patients. There were no serious adverse effects and no resistant organisms were isolated. The results of the study confirmed the safety and effectiveness of cefepime combined with a fluoroquinolone for the treatment of bone and joint infections caused by Gram-negative bacilli.

[Mitochondrial cytopathies associated with HIV infection]. / Cytopathies mitochondriales au cours de l'infection par le VIH.

The tremendous progress achieved during the last few years with the use of highly active antiretroviral therapy in suppressing HIV replication together with improvements in immunity have been tempered by a growing number of new adverse effects. Mitochondrial toxicity is one aspect of these long-term toxicities of antiretroviral drugs, with the role of nucleoside analogs particularly underlined. Some cases of impaired mitochondrial function have been clearly identified, such as pancreatitis due to didanosine, neuropathy due to zalcitabine, myopathy due to zidovudine, and lactic acidosis due to stavudine. These mitochondrial toxicities can affect several organs, presenting different patterns of symptoms: from asymptomatic to states with few symptoms despite huge metabolic abnormalities whose prognosis is immediately life-threatening. Beyond the inhibition of DNA polymerase gamma using nucleoside analogs, responsible for decreasing mitochondrial DNA in certain targeted organs, it appears that several physiopathologic mechanisms interact to explain this observed toxicity, HIV itself plays a role, and the underlying genetic pool needs to be better identified. Such cases mean that, it is imperative to avoid cumulated toxicities caused by associated treatments. With serious cases, or persistent symptoms despite discontinuing the nucleoside analogs responsible for such toxicity, one must propose vitamins, mitochondrial co-factors, or anti-oxidants. However, the future lies in the use of potent, less toxic nucleoside analogs, and in developing compounds belonging to other classes of antiretrovirals.

Suspected SARS patients hospitalised in French isolation units during the early SARS epidemic: The French experience.

During the SARS epidemic, many patients were screened according to WHO criteria but never went on to develop SARS. In May 2003, early in the epidemic, we conducted a retrospective study to describe suspected SARS patients hospitalised in France and compared them with documented cases of patients with SARS to evaluate the screening strategy. A total of 117 patients were studied. Only 3.4% had been in close contact with a SARS patient but 73.5% came from an affected area. 67.5% had fever and respiratory symptoms on their admission to hospital. 49.6% had fever and non specific symptoms. Clinical symptoms that were significantly more common among patients with SARS were fever, myalgia, dyspnoea, and nausea or vomiting. Presumed viral fever and respiratory tract infection were the most common diagnosis. Symptoms cannot be distinguished from an early stage of SARS confirming the usefulness of the WHO case definitions in isolation decision to avoid further transmission.

Suspected SARS patients hospitalised in French isolation units during the early SARS epidemic: the French experience.

During the SARS epidemic, many patients were screened according to WHO criteria but never went on to develop SARS. In May 2003, early in the epidemic, we conducted a retrospective study to describe suspected SARS patients hospitalised in France and compared them with documented cases of patients with SARS to evaluate the screening strategy. A total of 117 patients were studied. Only 3.4% had been in close contact with a SARS patient but 73.5% came from an affected area. 67.5% had fever and respiratory symptoms on their admission to hospital. 49.6% had fever and non specific symptoms. Clinical symptoms that were significantly more common among patients with SARS were fever, myalgia, dyspnoea, and nausea or vomiting. Presumed viral fever and respiratory tract infection were the most common diagnosis. Symptoms cannot be distinguished from an early stage of SARS confirming the usefulness of the WHO case definitions in isolation decision to avoid further transmission.

[Morbidity and cost of rotavirus infections in France]. / Morbidité et coût des infections à rotavirus en France.

BACKGROUND: Rotavirus is the most common cause of severe diarrhea in children. Morbidity and mortality related to rotavirus infection is not well known in temperate countries in general, and in France in particular. OBJECTIVES: The aim of this study was estimate the morbidity, mortality, and cost related to the rotavirus infection in France, in order to assess the potential impact of a vaccination program. METHODS: A birth cohort was followed until 5 years of age using a decision tree model. Rotavirus infection incidence rates were modeled according to age, seasons, and breast-feeding status. RESULTS: Based on estimates from a decision model, we found that in France, rotavirus infection was responsible for 300,000 annual episodes of acute diarrhea, 138,000 visits to general practitioners, 18,000 hospitalizations, and 9 deaths. The annual direct cost related to rotavirus infection care was estimated at 28 million euros. CONCLUSION: This study demonstrates the high morbidity and cost of care associated with rotavirus infection in France. The decision tree model developed in this study could be used in the future to estimate the potential effectiveness, cost and cost-effectiveness of childhood vaccination strategies using new rotavirus vaccines.

Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy.

BACKGROUND: Fatal lactic acidosis is a serious complication of therapy with nucleoside analogues. OBJECTIVE: To examine symptomatic hyperlactataemia in HIV-infected adults treated with antiretroviral drugs. METHODS: In this prospective study, arterial blood lactate levels were measured in patients presenting with unexplained clinical symptoms. When these levels were high, functional respiratory tests (FRT) were carried out. Liver or muscle biopsies were further proposed. Incidences were calculated by comparison with the entire cohort of patients treated in the department. RESULTS: Fourteen HIV-infected adults treated with antiretroviral drugs were identified with symptomatic hyperlactataemia during a 2-year period follow-up study. The incidence of hyperlactataemia was 0.8% per year but reached 1.2% if only patients treated with a regimen including stavudine were considered. Clinical symptoms included abnormal fatigue, tachycardia, abdominal pain, weight loss, peripheral neuropathy, and more specifically exercise-induced dyspnoea occurring despite effective antiretroviral treatment. FRT showed a metabolic deviation towards anaerobiosis with a high lactate/pyruvate ratio. Ultrastructural mitochondrial abnormalities were seen in all four patients for whom this was examined. There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction. Evolution was favourable in 13 patients, probably because of an early diagnosis. CONCLUSIONS: Potentially fatal adverse events occurring during antiretroviral treatment may be avoided by close monitoring of clinical signs and blood lactate levels. If other studies confirm that the cumulative long-term toxicity of antiretroviral drugs results from mitochondrial dysfunction, the incidence of hyperlactataemia and its clinical consequences may become more important.

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Prevention of human immunodeficiency virus-related opportunistic infections in France: a cost-effectiveness analysis.

A simulation model of human immunodeficiency virus (HIV) disease, which incorporated French data on the progression of HIV disease in the absence of antiretroviral therapy and on cost, was used to determine the clinical impact and cost-effectiveness of different strategies for the prevention of opportunistic infections in French patients who receive highly active antiretroviral therapy (HAART). Compared with use of no prophylaxis, use of trimethoprim-sulfamethoxazole (TMP-SMZ) increased per-person lifetime costs from euro 185,600 to euro 187,900 and quality-adjusted life expectancy from 112.2 to 113.7 months, for an incremental cost-effectiveness ratio of euro 18,700 per quality-adjusted life-year (euro/QALY) gained. Compared with use of TMP-SMZ alone, use of TMP-SMZ plus azithromycin cost euro 23,900/QALY gained; adding fluconazole cost an additional euro 54,500/QALY gained. All strategies that included oral ganciclovir had cost-effectiveness ratios that exceeded euro 100,000/QALY gained. In the era of HAART, on the basis of French data, prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium complex bacteremia is cost-effective. Prophylaxis against fungal and cytomegalovirus infections is less cost-effective than are other therapeutic options for HIV disease and should remain of lower priority.

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

A multicenter study of lomefloxacin and trimethoprim/sulfamethoxazole in the treatment of uncomplicated acute pyelonephritis.

A total of 63 adult patients with uncomplicated acute pyelonephritis were enrolled in a multicenter, randomized comparison of lomefloxacin (400 mg orally once daily for 14 days) and trimethoprim/sulfamethoxazole (TMP/SMX, 160/800 mg orally twice daily for 14 days). Study participants were predominantly female (70% in the lomefloxacin group and 80% in the TMP/SMX group). Escherichia coli was isolated from pretreatment urine cultures in 87.5% of the lomefloxacin group and 80.0% of the TMP/SMX group. Baseline pathogens were eradicated in 100% of evaluable patients in the lomefloxacin group 5-9 days after the end of therapy and in 88.9% of patients in the TMP/SMX group (p = 0.05). The clinical cure rate 5-9 days after therapy with lomefloxacin was 65.0% and for TMP/SMX was 68.4%. At the 4-6 week follow-up in the lomefloxacin group, nine pathogens remained eradicated, one E. coli was isolated, and the results for 14 pathogens were unknown or unevaluable. In the TMP/SMX group, 12 pathogens remained eradicated, three E. coli and one Group D Streptococcus were isolated, and the results for nine pathogens were unknown or unevaluable. Both treatment regimens were well tolerated; adverse events occurred in 12% of patients in the lomefloxacin group and in 17% in the TMP/SMX group. Events considered by the investigators to be probably related to treatment occurred in three patients in each group. In conclusion, once-daily lomefloxacin (400 mg) was a well tolerated and effective alternative to twice-daily TMP/SMX (160/800 mg) for the treatment of adults with uncomplicated acute pyelonephritis.

Plasma levels of sTNFR p75 and IL-8 in patients with HIV-1 infection.

We determined the degree of activation of the TNF alpha system and the levels of IL-8 in HIV-1 infection. TNF alpha is one of the most potent agents for the induction of IL-8. TNF alpha may be cleared rapidly from the circulation, however soluble tumor necrosis factor receptor (sTNFR) p75 which is more stable may reflect the degree of activation of the TNF alpha system. We measured concentrations of sTNFR p75 and IL-8 with immunoassays in the plasma of 99 HIV-1-infected patients at different stages of disease (Centers for Disease Control classification) and in 20 healthy control subjects. Plasma levels of sTNFR p75 were elevated in most of the asymptomatic seropositive patients without CD4+ T cell depletion (Stage IIA) and in most of patients of all clinical groups compared with controls. However, in the majority of those patients plasma levels of IL-8 were not higher than those of controls. Our results suggest that sTNFR p75 levels but not IL-8 levels in circulating blood are high in the course of HIV-1 infection.

Soluble tumor necrosis factor receptor type II (sTNFRII) in HIV-infected patients: relationship with the plasma level of HIV-1 RNA.

The value of soluble receptor for tumor necrosis factor type II (sTNFRII) as a strong and early predictor of HIV disease progression was suggested. Recently it has been reported that sTNFRII may provide an indication of the HIV load. In this work we focused on the relationship between sTNFRII and HIV burden in 95 HIV-1+ patients without AIDS grouped according to the 1993 classification of the CDC as group A, n = 55, and group B, n = 40. Compared with healthy controls, higher values of sTNFRII were obtained in all groups of HIV-1 infected patients (P < 0.001), but we found no inverse correlation between sTNFRII and CD4+ lymphocyte counts in CDC group A and B of the disease, and no correlation with log RNA copy number in patients with CD4 T-cell counts > 499/microl. A correlation was obtained between sTNFRII and the viral load in patients with CD4 T-cell counts ranging from 200 to 499/microl, but only in CDC group B patients (P < 0.01, n = 26). There was no correlation between the variations of sTNFRII and HIV-1 RNA levels in 19 CDC group A and 15 CDC group B clinically stable patients in the course of a short follow up. The plasma level of sTNFRII do not appear as a valuable surrogate marker of the plasma level of HIV-1 RNA in patients. Further investigations are needed to define the mechanism of the raised level of sTNFRII in HIV-1 infected patients.

Antibodies to the nef protein and to nef peptides in HIV-1-infected seronegative individuals.

The silent period that follows infection by the human immunodeficiency virus (HIV-1) and precedes seroconversion remains a problem for the screening of blood supply, and knowledge about the mechanism involved in the maintenance of latency is only fragmentary. Using purified nef recombinant protein and six synthetic nef peptides, antibodies to the product of an HIV-1 regulatory gene, the negative regulatory factor (nef) involved in maintenance of proviral latency, were detected by Western blot and radioimmunoassay techniques in HIV-1-seronegative, viral antigen-negative, and virus culture-negative individuals at risk for HIV infection. This antibody response to nef was correlated in eight individuals with the detection of HIV-1 proviral DNA by oligonucleotide hybridization, following enzymatic amplification of HIV DNA in peripheral blood mononuclear cells. Such latent HIV infections have now been followed for up to 6 or 10 months in five individuals. In addition, retrospective and prospective analysis of HIV-1-seropositive individuals have shown (1) antibodies to nef preceding seroconversion, and (2) the persistence of antibodies to nef and of HIV-1 proviral DNA in a case of spontaneous complete HIV-1 seronegativation. Since DNA amplification cannot be currently considered for routine use, screening for anti-nef antibodies followed by confirmation by DNA amplification could represent a basis for new diagnostic strategies. Beyond their diagnostic implications, these findings, suggesting that regulatory genes of the HIV-1 provirus can be expressed prior to the initiation of virion synthesis, may also be applicable in the design of alternative vaccines against the acquired immunodeficiency syndrome.

In HIV-1-infected patients, plasma levels of HIV-1 RNA are inversely correlated with IFN-alpha responsiveness of whole-blood cultures to sendai virus.

BACKGROUND: A diminished or totally blocked IFN-alpha production in cells from HIV-1-infected patients has been reported. OBJECTIVE: To investigate the relationship between the decreased in vitro production of IFN-alpha and the plasma level of HIV-1 RNA. STUDY DESIGN: Whole blood samples of 39 healthy subjects and 44 HIV-1-infected patients were incubated in the presence of Sendai virus for 24 h. IFN-alpha contained in supernatants was assayed by using an immunochemical method (DELFIA) and by using an antiviral assay. Plasma HIV-1 RNA was measured by the Amplicor HIV-1 monitor test. RESULTS: The levels of IFN-alpha obtained were significantly lower in cultures from HIV-1 infected patients than in control subjects (P<0.0001). The antiviral activity in supernatants of Sendai virus-activated whole-blood cultures, assayed by protection of MDBK cells against vesicular stomatitis virus (VSV), was significantly lower in cultures from HIV-1 infected patients than in corresponding controls (P<0.0001). IFN-alpha values determined by DELFIA and those determined by bioassay were significantly correlated. In vitro production of IFN-alpha by whole-blood cultures correlated well with the plasma levels of HIV-1 RNA (P<0.001). CONCLUSIONS: In HIV-infected patients an increased rate of HIV-1 replication is associated with reduced responsiveness to induction of IFN-alpha by indicator virus, suggesting that HIV-1 replication causes impaired production of IFN-alpha by blood cells or vice-versa.

Incidence of primary opportunistic infections in two human immunodeficiency virus-infected French clinical cohorts.

BACKGROUND: Clinical guidelines for the prevention of opportunistic infections in human immunodeficiency virus (HIV)-infected individuals have been developed on the basis of natural history data collected in the USA. The objective of this study was to estimate the incidence of primary opportunistic infections in HIV-infected individuals in geographically distinct cohorts in France. METHODS: We conducted our study on 2664 HIV-infected patients from the Tourcoing AIDS Reference Centre and the hospital-based information system of the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine enrolled from January 1987 to September 1995 and followed through December 1995. We estimated: (1) CD4-adjusted incidence rates of seven primary opportunistic infections in the absence of prophylaxis for that specific infection or any antiretroviral drugs other than zidovudine; and (2) CD4 lymphocyte count decline. RESULTS: The highest incidence rates for all opportunistic infections studied occurred in patients with CD4 counts < 200/microl. With CD4 counts < 50/microl, the most common opportunistic infections were toxoplasmic encephalitis (12.6 per 100 person-years) and Pneumocystis carinii pneumonia (11.4 per 100 person-years). Mycobacterium tuberculosis was the least common opportunistic infection (< 5.0/100 person-years). Even with CD4 counts > 300/microl, cases of Pneumocystis carinii pneumonia and toxoplasmic encephalitis were reported. The mean CD4 lymphocyte decline per month was 4.6 cells/microl. There was a significant association between HIV risk behaviour and the incidence of cytomegalovirus infection, between calendar year and the incidence of Pneumocystis carinii pneumonia, toxoplasmic encephalitis and Candida esophagitis, and between geographical area and the incidence of Pneumocystis carinii pneumonia and cytomegalovirus infection. CONCLUSIONS: Geographical differences exist in the incidence of HIV-related opportunistic infections. These results can be used to define local priorities for prophylaxis of opportunistic infections.