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Biomedical subjects

M French

Publications and source records attributed to M French.

At least 19 recordsLinked to original sources
PubMed2001

HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, open-label, multicentre study.

BACKGROUND: Lipodystrophy, dyslipidaemia and insulin resistance often complicate protease inhibitor-containing antiretroviral therapy. The aims of this study were to determine if these are reversible with continued HIV suppression following protease inhibitor substitution. METHODS: Eighty-one HIV protease inhibitor recipients (78 male; mean antiretroviral therapy, 55 months) with predominant peripheral lipoatrophy, HIV RNA < 400 copies/ml plasma for at least the preceding 6 months, and no prior abacavir, non-nucleoside analogue or adefovir therapy were randomized 3 : 2 to continue nucleoside analogues and substitute protease inhibitor(s) with abacavir, nevirapine, adefovir and hydroxyurea (n = 49) or to continue all therapy (n = 32) with an option to switch at week 24. The primary endpoints were total body fat and HIV RNA at week 24. Other assessments were regimen safety, regional body composition, metabolic parameters, quality of life, and CD4 T-lymphocyte counts to week 48. RESULTS: There was a greater decline in total body fat in the switch group than in the continue group (-1.6 and -0.4 kg, respectively at week 24; P = 0.006). This comprised greater declines in limb and subcutaneous abdominal fat, and in intra-abdominal fat of patients with moderate or severe abdominal fat accumulation. Viral suppression was similar, despite 18 (37%) switch group patients ceasing at least one study drug by week 24 because of adverse events. Total cholesterol and triglycerides declined more in the switch group (both P < 0.002). High density lipoprotein cholesterol increased significantly in both groups at week 48 (P < 0.02). There was no change for any glycaemic parameter. CONCLUSIONS: In predominantly lipoatrophic patients, switching from HIV protease inhibitor therapy lead to improved lipids and less intra-abdominal fat, but also to less peripheral fat, and had minimal effect on insulin resistance. Virological control in these heavily pretreated patients was unaffected, despite frequent switch drug cessations.

Adenine↗
PubMed2001

Cerebral mycobacterium avium infection in an HIV-infected patient following immune reconstitution and cessation of therapy for disseminated mycobacterium avium complex infection.

Reported here is a case of cerebral Mycobacterium avium complex infection that occurred in an HIV-infected patient, who had been treated for disseminated infection and had discontinued clarithromycin and ethambutol following a significant rise in his CD4+ T-cell count after starting highly active antiretroviral therapy. He responded well to excision of the lesion and reinstitution of multidrug therapy. Caution should be exercised when considering ceasing maintenance therapy for disseminated Mycobacterium avium complex infection in HIV-infected patients who demonstrate an apparently good immunologic response to highly active antiretroviral therapy, as this response may not necessarily restore protective immunity against all opportunistic pathogens.

AIDS-Related Opportunistic Infections↗
PubMed2000

A randomised, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo1 study.

BACKGROUND: Highly active antiretroviral therapy (HAART) including two nucleoside analogues and a potent protease inhibitor is standard of care initial therapy for HIV-infected adults. The best-tolerated and most potent initial HAART regimen is unknown and was investigated in this study. METHODS: One hundred and nine HIV-infected adults with no prior antiretroviral therapy, and CD4 lymphocyte counts < 500 x 10(6) cells/l or plasma HIV RNA > 30,000 copies/ml were randomized to zidovudine-lamivudine-indinavir (ZDV-3TC-IDV), stavudine-lamivudine-indinavir (d4T-3TC-IDV) or stavudine-didanosine-indinavir (d4T-ddI-IDV) for 52 weeks. The primary endpoints were plasma HIV RNA and drug-related adverse events. Other assessments were overall safety, adherence and adverse events, CD4 lymphocyte counts, cutaneous delayed type hypersensitivity (DTH) responses and quality of life (Euroqol). RESULTS: Only 58% patients had HIV RNA < 50 copies/ml plasma at 12 months, with no significant difference between the three regimes (P = 0.34). Drug-related adverse events sufficiently severe to warrant drug discontinuation were less common (P = 0.06) in patients receiving d4T-3TC-IDV (18%) than in those receiving ZDV-3TC-IDV (34%) or d4T-ddI-IDV (41%). The percentages of patients who remained on their assigned therapy with plasma HIV RNA < 50 copies/ml at 52 weeks were 60% with d4T-3TC-IDV, 53% with ZDV-3TC-IDV and 35% with d4T-ddI-IDV. Virological failure at 52 weeks was more likely in those whose adherence was estimated to be < 100% in the first 4 weeks of therapy (P = 0.02), but not in those who developed grade 3 or 4 drug-related adverse events. At 52 weeks, the mean CD4 lymphocyte count increase was 200 x 10(6) cells/l with only 7% of patients having counts lower than at baseline; DTH responses improved but remained clinically impaired in most patients. Quality of life improved significantly in all groups. CONCLUSIONS: Initial HAART regimens including IDV failed to suppress plasma HIV RNA to < 50 copies/ml in > 40% patients after only 12 months of therapy although there was significant overall improvement immunologically and in quality of life. The type of dual nucleoside combination used was less important in predicting virological failure than was imperfect adherence early in therapy. Consideration should be given to modifying a HAART regimen relatively early in non-adherent patients.

Adult↗
PubMed2000

Ligand-dependent regulation of vascular endothelial growth factor and erythropoietin expression by a plasmid-based autoinducible GeneSwitch system.

We investigated the ability of an improved mifepristone-dependent GeneSwitch system to regulate the expression of genes for two therapeutic proteins: vascular endothelial growth factor (VEGF) and erythropoietin. The GeneSwitch system consisted of two plasmids, one encoding the chimeric GeneSwitch protein, the other an inducible transgene. When the constitutive CMV promoter of the GeneSwitch plasmid was replaced by an autoinducible promoter consisting of four copies of GAL4 DNA binding sites linked to a minimal thymidine kinase promoter, the tightness of transgene regulation was improved by an order of magnitude. Quantitative RT-PCR analysis of GeneSwitch mRNA confirmed that the autoinducible promoter was responsive to mifepristone. We demonstrated the ability of the improved GeneSwitch system to regulate the expression of VEGF or erythropoietin in a biologically relevant manner after delivery of plasmids to the hind-limb muscle of adult mice. This ability of the autoinducible GeneSwitch system to regulate the expression of therapeutic proteins in mice indicates its potential for use in human gene therapy applications.

Animals↗
PubMed2000

Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes.

PURPOSE: To design, synthesize, and test synthetic glycopeptide-based delivery systems for gene targeting to hepatocytes by systemic administration. METHODS: All peptides were synthesized by the solid phase method developed using Fmoc chemistry on a peptide synthesizer. The binding of galactosylated peptides to HepG2 cells and accessibility of the galactose residues on particle surface was demonstrated by a competition assay using 125I-labeled asialoorosomucoid and RCA lectin agglutination assay, respectively. DNA plasmid encoding chloramphenicol acetyl transferase (CAT) gene was complexed with a tri-galactosylated peptide (GM245.3) or tri-galactosylated lipopeptide (GM246.3) in the presence of an endosomolytic peptide (GM225.1) or endosomolytic lipopeptide (GM227.3) to obtain DNA particles of 100-150 nm in size. The plasmid/peptide complexes were added to HepG2 cell cultures or intravenously administered by tail vein injection into normal mice or rats. Plasmid uptake and expression was quantified by qPCR and ELISA, respectively. RESULTS: Multiple antennary glycopeptides that have the ability to condense and deliver DNA plasmid to hepatocytes were synthesized and complexed with DNA plasmid to obtain colloidally stable DNA/peptide complexes. Addition of DNA/GM245.3/GM225.1 peptide complexes (1:3:1 (-/+/-)) to HepG2 cell cultures yielded CAT expression in transfected cells. The transfection efficiency was significantly reduced in the absence of galactose ligand or removal of endosomolytic peptide. Intravenous administration of DNA/GM245.3 peptide complexes (1:0.5 (-/+)) into the tail vein of normal rats yielded DNA uptake in the liver. Substitution of GM245.3 by galactosylated lipopeptide GM246.3 resulted in more stable DNA particles, and a 10-fold enhancement in liver plasmid uptake. CAT expression was detectable in liver following intravenous administration of DNA/GM246.3 complexes. Addition of endosomolytic lipopeptide GM227.3 into the complexes (DNA/ GM246.3/GM227.3 (1:0.5:1 (-/+/-))) yielded a 5-fold increase in CAT expression. Liver expression was 8-fold and 40-fold higher than lung and spleen, respectively, and localized in the hepatocytes only. The transfection efficiency in liver was enhanced by increasing DNA dose and injection volume. The plasmid uptake and expression in liver using DNA/GM246.3/GM227.3 complexes was 100-200-fold higher than DNA formulated in glucose. Tissue examination and serum biochemistry did not show any adverse effect of the DNA/GM246.3/ GM227.3 (1:0.5:1 (-/+/-)) complexes after intravenous delivery. CONCLUSIONS: Gene targeting to hepatocytes was achieved by systemic administration of a well-tolerated synthetic glycopeptide-based delivery system. The transfection efficiency of this glycopeptide delivery system was dependent on peptide structure, endosomolytic activity, colloidal particle stability, and injection volume.

Amino Acid Sequence↗
PubMed2000

A comparison of nonlinear regression and neural network models for ground-level ozone forecasting.

A hybrid nonlinear regression (NLR) model and a neural network (NN) model, each designed to forecast next-day maximum 1-hr average ground-level O3 concentrations in Louisville, KY, were compared for two O3 seasons--1998 and 1999. The model predictions were compared for the forecast mode, using forecasted meteorological data as input, and for the hindcast mode, using observed meteorological data as input. The two models performed nearly the same in the forecast mode. For the two seasons combined, the mean absolute forecast error was 12.5 ppb for the NLR model and 12.3 ppb for the NN model. The detection rate of 120 ppb threshold exceedances was 42% for each model in the forecast mode. In the hindcast mode, the NLR model performed marginally better than the NN model. The mean absolute hindcast error was 11.1 ppb for the NLR model and 12.9 ppb for the NN model. The hindcast detection rate was 92% for the NLR model and 75% for the NN model.

Forecasting↗
PubMed1999

Ligand-dependent regulation of plasmid-based transgene expression in vivo.

As gene therapy advances, the ability to regulate transgene expression will become paramount for safety and efficacy. In this study, we investigate the ability of the mifepristone-dependent GeneSwitch system to regulate the expression of trangenes delivered to mice by nonviral methods. Two plasmids, one encoding the chimeric GeneSwitch protein, the other an inducible transgene for secreted human placental alkaline phosphatase (SEAP), were delivered to the hind-limb muscles of adult mice. Modulation of the level of secretion of the transgene product into serum was achieved by intraperitoneal administration of low doses of the drug mifepristone (MFP). The EC50 for induction of transgene expression by MFP was 0.03 +/- 0.005 mg/kg. The maximal level of transgene expression after induction was equal to or higher than that displayed by a plasmid driven by the CMV enhancer/promoter. The average magnitude of induction was 14- to 19-fold. Multiple rounds of drug-dependent regulation of transgene expression in vivo were demonstrated. In BALB/c mice, the ability to regulate transgene expression persisted for approximately 3 weeks, until the appearance of neutralizing antibodies to the secreted transgene product. In immune-deficient mice, the ability to repetitively regulate transgene expression persisted for at least 5 weeks. Although the dynamic range of regulation needs improvement, the plasmid-based GeneSwitch system has features that are attractive for gene therapy applications.

Alkaline Phosphatase↗
PubMed1999

Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of angiostatic factors should be a viable approach for cancer gene therapy. Endostatin, a potent angiostatic factor, was expressed in mouse muscle and secreted into the bloodstream for up to 2 weeks after a single intramuscular administration of the endostatin gene. The biological activity of the expressed endostatin was demonstrated by its ability to inhibit systemic angiogenesis. Moreover, the sustained production of endostatin by intramuscular gene therapy inhibited both the growth of primary tumors and the development of metastatic lesions. These results demonstrate the potential utility of intramuscular delivery of an antiangiogenic gene for treatment of disseminated cancers.

Animals↗
PubMed1999

The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases.

An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the clearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150-200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA-B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis to the central MHC between HLA-B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1-associated diseases are more closely associated with HLA-DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen-independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co-factor in the diverse immunopathological conditions associated with the 8.1 AH.

Animals↗
PubMed1998

Biodistribution and gene expression of lipid/plasmid complexes after systemic administration.

The objectives of this study were to investigate the influence of physicochemical properties of lipid/plasmid complexes on in vivo gene transfer and biodistribution characteristics. Formulations based on 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and novel biodegradable cationic lipids, such as ethyl dioleoyl phosphatidylcholine (EDOPC), ethyl palmitoyl myristyl phosphatidylcholine (EPMPC), myristyl myristoyl carnitine ester (MMCE), and oleyl oleoyl L-carnitine ester (DOLCE), were assessed for gene expression after tail vein injection of lipid/plasmid complexes in mice. Gene expression was influenced by cationic lipid structure, cationic lipid-to-colipid molar ratios, plasmid-to-lipid charge ratios, and precondensation liposome size. Detectable levels of human growth hormone (hGH) in serum, human factor IX (hFIX) in plasma, and chloramphenicol acetyltransferase (CAT) in the lung and liver were observed with positively charged lipid/plasmid complexes prepared from 400-nm extruded liposomes with a cationic lipid-to-colipid ratio of 4:1 (mol/mol). Intravenous administration of lipid/CAT plasmid complexes resulted in distribution of plasmid DNA mainly to the lung at 15 min after injection. Plasmid DNA accumulation in the liver increased with time up to 24 hr postinjection. There was a 10-fold decrease in the amount of plasmid DNA in the lung at 15 min after injection, when the lipid/plasmid complex charge ratio was decreased from 3:1 to 0.5:1 (+/-). Bright fluorescent aggregates were evident in in vivo-transfected lung with the positively charged pCMV-CAT/DOLCE:dioleyl phosphatidylethanolamine (DOPE) (1:1, mol/mol) complexes, while more discrete punctate fluorescence was observed with a 4:1 molar ratio of cationic lipid:colipid formulations. Preinjection of polyanions such as plasmid, dextran sulfate, polycytidic acid, and polyinosinic acid decreased hGH expression, whereas the preinjection of both positively charged and neutral liposomes had no effect on hGH serum levels. Of the cationic lipids tested, DOLCE was found to be the most effective potentially biodegradable cationic lipid. A correlation between gene expression and cationic lipid:colipid ratios and lipid-to-plasmid charge ratio was also observed for DOTMA- and DOLCE-based formulations.

Animals↗
PubMed1998

Treatment response and durability of a double protease inhibitor therapy with saquinavir and ritonavir in an observational cohort of HIV-1-infected individuals.

OBJECTIVE: To evaluate treatment response, durability and tolerance of a four-drug regimen including saquinavir and ritonavir in combination with either zidovudine/lamivudine or stavudine/lamivudine. DESIGN: Observational cohort of HIV-positive individuals. METHODS: Viral load, CD4+ and CD8+ T lymphocyte counts were assessed at intervals of 1-3 months in subjects commencing therapy between July 1996 and November 1996. Adverse events were evaluated as well as risk factors for therapeutic failures. RESULTS: A group of 56 male patients were included and followed for 48 weeks. Of these, 66% had already taken a protease inhibitor. Viral load dropped by a median 1.98 log10 HIV RNA copies/ml from baseline (interquartile range: 1.49-2.46) and became undetectable (< 400 copies/ml) in 68% of patients. Response varied: 9% were non-responders (HIV RNA reduction < 0.5 log10 copies/ml) and 23% were incomplete responders (nadir of HIV RNA > 400 copies/ml). After 48 weeks, viral load remained undetectable in 49%. Median CD4+ T lymphocyte count increased from 191 x 10(6) to 418 x 10(6) cells/l (range, 241-537 x 10(6) cells/l). Although protease inhibitor and nucleoside pretreatment selected for drug-resistant viral mutants, only the protease inhibitor experience was identified as a risk factor for therapeutic failure. Adverse events occurred in 73% of patients and led to a change of therapy in 9%. CONCLUSION: Despite advanced HIV disease and pretreatment with multiple antiretroviral drugs, a strong initial treatment response to this drug regimen was observed. However, virological failure occurred in 51% of patients after 48 weeks and frequent adverse events complicated therapy.

Adult↗
PubMed1998

Outpatient continuous intravenous interleukin-2 or subcutaneous, polyethylene glycol-modified interleukin-2 in human immunodeficiency virus-infected patients: a randomized, controlled, multicenter study. Australian IL-2 Study Group.

The safety and activity of outpatient-based continuous intravenous interleukin-2 (CIV IL-2) or a slow-release, polyethylene glycol (PEG)-modified IL-2 were studied in human immunodeficiency virus (HIV)-infected persons with CD4 cell counts between 200 and 500/mm3. One hundred fifteen patients were randomized to antiretroviral therapy plus cyclical CIV IL-2 (n = 27), subcutaneous PEG IL-2 (n = 58), or no IL-2 (n = 30). Toxicity withdrawal rates were low (4% for CIV IL-2 and 7% for PEG IL-2). There were median CD4 cell count increases of 359 and 44 cells/mm3 and a decline of 46 cells/mm3 in the 3 groups, respectively, over 1 year (P < .0001 for each intergroup comparison). CD4 cell count increases were greatest in those with lower HIV RNA load. Delayed-type hypersensitivity scores increased and HLA-DR expression on CD8 cells decreased significantly with IL-2 therapy. HIV RNA levels were unaffected. IL-2 therapy may expand the existing immune repertoire but not immediately reconstitute lost immune function.

Adult↗
PubMed1998

Complementary expression of HIP, a cell-surface heparan sulfate binding protein, and perlecan at the human fetal-maternal interface.

The human hemochorial placenta is a structure formed by the invasion of cytotrophoblasts into the uterus. Previous studies from our laboratory have demonstrated a role for heparan sulfate proteoglycans (HSPGs) and their binding proteins in interactions between human trophoblastic and uterine cell lines in vitro. In this study, expression of both mRNA and protein of a novel, cell surface, heparin/heparan sulfate interacting protein (HIP), by human trophoblastic cell lines-i.e., JAR, JEG, and BeWo-and by human cytotrophoblast was examined throughout gestation. Immunohistochemistry of the human fetal-maternal interface demonstrated abundant HIP expression in cytotrophoblast cells, with lesser staining in syncytiotrophoblast and little or no staining in surrounding stromal or decidual cells. Staining with antibodies to the basement membrane HSPG, perlecan, demonstrated a pattern of staining complementary to that of HIP. Cytotrophoblasts in the uterine stroma, not affiliated with attached villi, displayed a less intense deposition of perlecan. In vitro binding studies of 125I-perlecan to a 17-amino acid synthetic peptide sequence of HIP, which has a high affinity and specificity for heparin/heparan sulfate, indicates that perlecan binds to the HIP peptide with high affinity (KDapp = 0.6 nM) and in a heparin-inhibitable manner. Furthermore, HIP antibodies inhibited by 61-88% in vitro invasion by trophoblasts in assays using primary cultures of normal human cytotrophoblasts. Consistent with this was the observation that immunohistochemically detectable HIP expression was greatly reduced in pre-eclamptic cytotrophoblasts, a condition in which trophoblast invasion is abnormally shallow. It is suggested that HIP potentiates human cytotrophoblast interactions with HSPGs, in vivo, and facilitates trophoblast invasion processes.

Antibodies↗
PubMed1998

Coresistance to zidovudine and foscarnet is associated with multiple mutations in the human immunodeficiency virus type 1 reverse transcriptase.

Human immunodeficiency virus type 1 (HIV-1) isolates obtained from a patient with AIDS were assessed for coresistance to foscarnet and zidovudine. An HIV-1 strain (AP20) coresistant to foscarnet and zidovudine was isolated after 20 months of continuous combination therapy. The reverse transcriptase (RT) gene of AP20 had 41 substitutions which were different from the HXB2-D sequence and 9 that were different from the sequence of its foscarnet-sensitive, zidovudine-resistant progenitor virus (AP6). Six of these mutations were nonpolymorphic (T39A, V108I, K166R, K219R, K223Q, and L228R). Both strains had the conventional mutations mediating zidovudine resistance. In vivo selection may result in HIV-1 strains that are coresistant to foscarnet and zidovudine, but coresistance appears to require a complex evolutionary path and multiple RT mutations.

Amino Acid Sequence↗
PubMed1998

Noninvasive detection of allograft rejection in heart transplant recipients by use of Doppler tissue imaging.

BACKGROUND: Allograft rejection in heart transplant recipients is associated with lymphocytic extracellular infiltration and edema resulting in increased myocardial stiffness and abnormal relaxation. We hypothesize that these abnormalities will result in reduced myocardial relaxation velocities. Doppler tissue imaging is a novel noninvasive imaging modality that is capable of quantifying myocardial tissue velocities and may therefore be useful to identify allograft rejection. METHODS: In this observational study, 121 heart transplant recipients underwent pulsed-wave Doppler tissue imaging at the time of their surveillance endomyocardial biopsies. Peak relaxation and systolic velocities were measured from the inferior wall blinded to clinical biopsy. Biopsy results were classified as rejecting (3a, 3b, 4) or nonrejecting (0, 1a, 1b). RESULTS: The peak relaxation velocity in nonrejecting allograft recipients (n = 98) was 0.21 m/sec +/- 0.01. During moderate allograft rejection (n = 16), peak relaxation velocities decreased to 0.14 m/sec +/- 0.01 (p < 0.0001), and subsequently increased to 0.23 m/sec +/- 0.0 after successful treatment (p = 0.0001). Peak systolic velocities did not change during rejection, 0.08 m/sec +/- 0.02 when compared with nonrejecting recipients 0.09 +/- 0.02 (p = NS). With a cutoff value of less than 0.16 m/sec, the sensitivity of peak myocardial relaxation velocities for detection of rejection was 76%. The specificity and negative predictive values were 88% and 92%, respectively. CONCLUSION: Moderate allograft rejection results in reduced myocardial relaxation velocities, which can be detected noninvasively with pulsed-wave Doppler tissue imaging. Hence, Doppler tissue imaging is a useful noninvasive tool to exclude allograft rejection.

Adult↗
PubMed1998

Altered natural history of AIDS-related opportunistic infections in the era of potent combination antiretroviral therapy.

Since potent HIV protease inhibitor drugs became widely available in early 1996, many HIV clinical specialists have noted a marked decrease in the occurrence of AIDS-related opportunistic infections, and some specialists have reported unusual clinical presentations and manifestations of previously common opportunistic infections. In this article, we will review (1) the available data regarding recent trends in AIDS-related opportunistic infections incidence and manifestations, (2) clinical and immunologic evidence that potent combination antiretroviral therapy can alter the natural history of these opportunistic infections, and (3) the implications of these findings for current patient management practice and future clinical and immunologic research. As a preface to this review, however, it is important to acknowledge that any evaluation of the potential benefit of potent combination antiretroviral therapy in reducing the risk of serious opportunistic infections can be confounded by the concomitant use of prophylactic antimicrobial agents co-administered to prevent specific opportunistic infections. For example, it is standard clinical practice to administer trimethoprim-sulfamethoxazole (or another agent if trimethoprim-sulfamethoxazole cannot be tolerated) to patients with an absolute CD4 lymphocyte count < 200 cells/microliters, unexplained chronic fever or a history of oropharyngeal candidiasis. Similarly, specific antimicrobial prophylaxis to prevent disseminated Mycobacterium avium complex (MAC) infection in patients with absolute CD4 counts < 50 cells/microliters is also a widely recommended guideline. Although the relative efficacies of specific antimicrobial prophylaxis regimens in preventing the most common life- and sight-threatening opportunistic infectious complications of AIDS [Pneumocystis carinii pneumonia (PCP), disseminated MAC infection, and cytomegalovirus (CMV) retinitis] are now well established, these relative efficacies were established in the era before potent combination antiretroviral therapies became available and may not be generalizable to the current era. Nevertheless, for perspective, the reported efficacies of prophylaxis for PCP, disseminated MAC infection, and CMV end-organ disease are summarized in Table 1.

AIDS-Related Opportunistic Infections↗