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Charles C J Carpenter

Publications and source records attributed to Charles C J Carpenter.

At least 19 recordsLinked to original sources
PubMed2006

Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel.

CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

Adult↗
PubMed2006

Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India.

OBJECTIVE: To describe reasons for modification and discontinuation of antiretroviral regimens in association with adverse events (AEs), treatment failure, and cost among patients in southern India. METHODS: Secular trends of patients initiating highly active antiretroviral therapy (HAART) between January 1996 and October 2004 at a tertiary HIV referral center in India were analyzed using a previously validated natural history database. RESULTS: All previously antiretroviral therapy-naive patients who initiated HAART (N = 1443) and had at least 1 follow-up visit were evaluated. The median CD4 count at the time of initiating HAART was 108 cells/microL. The most common first-line regimens were stavudine (d4T) plus lamivudine (3TC) plus nevirapine (NVP) (63%), zidovudine (AZT) plus 3TC plus NVP (19%), d4T plus 3TC plus efavirenz (EFV) (9%), and AZT plus 3TC plus EFV (4%). Twenty percent of patients modified their first-line regimen. The most common reason for modifying therapy was the development of an AE (64%), followed by cost (19%) and treatment failure (14%), with median times to modify therapy being 40, 151, and 406 days, respectively. Common AEs were itching and/or skin rash (66%), hepatotoxicity (27%), and anemia (23%). Nine percent of patients discontinued therapy entirely after a median duration of 124 days, primarily because of cost (64%). CONCLUSION: The most common reason for modifying therapy was the occurrence of AEs, whereas cost was the most common reason for discontinuing therapy. Despite increasing access to lower cost generic HAART in India, even less expensive and more tolerable first-line regimens and cost-effective treatment monitoring tools need to be introduced to achieve better treatment outcomes and access in resource-constrained settings.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Rapid viral load suppression following generic highly active antiretroviral therapy in Southern Indian HIV-infected patients.

We prospectively studied the initial results of 6 months of generic efavirenz-based therapy on the plasma viral load in 40 patients at YRG Centre for AIDS Research and Education, a tertiary HIV referral centre in southern India. The median baseline plasma viral load was 259,000 copies/ml and at 6 months 95% of patients had plasma viral loads less than 400 copies/ml. The data support the use of generic non-nucleoside reverse transcriptase inhibitor-based regimens in resource-limited settings.

Adult↗
PubMed2005

It is time to implement routine, not risk-based, HIV testing.

Approximately one-quarter of a million persons in the United States who are infected with human immunodeficiency virus (HIV) do not know it. To decrease the number of such persons, primary care providers should make HIV testing a routine component of health care. HIV testing should also be offered routinely in other settings, such as emergency departments, jails, and substance abuse treatment centers. Currently, the Centers for Disease Control and Prevention and the Infectious Diseases Society of America recommend routine HIV testing only in settings where the prevalence of HIV infection is > or =1%; in settings where the prevalence of HIV infection is <1%, testing should be based on risk assessment. Because of the impracticality of strategies for testing that are based on estimates of prevalence, and because of the inaccuracy of risk assessment, we propose that HIV testing be routinely offered to any person who is sexually active. As an adjunct to the implementation of routine testing programs, counseling practices need to be streamlined, and rapid HIV testing needs to be implemented in the appropriate settings.

Diagnostic Tests, Routine↗
PubMed2004

Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel.

CONTEXT: Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection. OBJECTIVE: To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails. DATA SOURCES: Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management. STUDY SELECTION: Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004. DATA EXTRACTION: Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached. DATA SYNTHESIS: Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel). CONCLUSION: Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.

Adult↗
PubMed2004

Changes in total lymphocyte count as a surrogate for changes in CD4 count following initiation of HAART: implications for monitoring in resource-limited settings.

BACKGROUND: A major obstacle to the administration of highly active antiretroviral therapy (HAART) in resource-limited settings is the high cost of CD4 count testing. The total lymphocyte count (TLC) has been proposed as a surrogate marker to monitor immune response to therapy. OBJECTIVE: To assess, in a developed country setting, the capability and clinical utility of TLC change as a surrogate marker for CD4 count change in monitoring patients on HAART. METHODS: Longitudinal co-variation between changes in TLC and concomitant changes in CD4 count following the initiation of HAART was examined using a retrospective cohort study of 126 HIV-positive patients attending The Miriam Hospital, Brown University, Providence, RI. Analyses included evaluation of the direction of TLC change as a marker for direction of CD4 change, using sensitivity and specificity; evaluation of absolute change in TLC as a marker for benchmark changes in CD4 (> or =50 over 6 months, > or =100 over 12 months), using receiver-operator characteristic (ROC) curves; and a regression model of change in TLC as a function of change in CD4, to understand within-individual variation of longitudinal TLC measures. RESULTS: In the first 24 months of HAART, the sensitivity of a TLC increase as a marker for CD4 count increase over the same time period ranged from 86-94%, and the specificity ranged from 80-85%. The median change in TLC among patients with a CD4 count rise of > or =100 cells/mm at 1 year of HAART was +766 cells/mm while that of patients with a CD4 count rise of <100 cells/m was +100 cells/mm. The area under the corresponding ROC curve was 0.89, suggesting that change in TLC discriminates well between those with 1-year CD4 change of > or =100 vs. those with change <+100. From a regression analysis, we found that mean change in TLC per 1 cell/mm change in CD4 count was 7.3 (SE 1.2, P < 0.001). The degree of this association varied from individual to individual but was positive for all individuals. CONCLUSIONS: Within the first 2 years of HAART, the direction of change in TLC appears to be a strong marker for direction of concomitant change in CD4 count (sensitivity 86-94% and specificity 80-85%, depending on length of interval). Positive and negative predictive values depend on the proportion of CD4 changes that are positive. In this cohort, that proportion is 87.9%, which yields high positive predictive value (96-98%) but lower negative predictive value (43-63%). Findings from the regression model suggest that taking multiple measurements of TLC at more frequent intervals may reduce variability and potentially improve predictive accuracy.

Adolescent↗
PubMed2004

Engineering immunogenic consensus T helper epitopes for a cross-clade HIV vaccine.

Developing a vaccine that will stimulate broad HIV-specific T cell responses is difficult because of the variability in HIV T cell epitope sequences, which is in turn due to the high mutation rate and consequent strain diversity of HIV-1. We used a new Class II version of the EpiMatrix T cell epitope-mapping tool and Conservatrix to select highly conserved and promiscuous Class II HLA-restricted T cell epitopes from a database of 18,313 HIV-1 env sequences. Criteria for selection were: (1) number of HIV-1 strains represented as measured by Conservatrix; (2) EpiMatrix score; and (3) promiscuity (number of unique MHC motifs contained in the peptide). Using another vaccine design tool called the EpiAssembler, a new set of overlapping, conserved and immunogenic HIV-1 peptides were engineered creating extended "immunogenic consensus" sequences. Each overlapping 9-mer of the 20-23 amino acid long immunogenic consensus peptides was conserved in a large number (range 893-2254) of individual HIV-1 strains, although the novel peptides were not representative of any single strain of HIV. We synthesized nine representative peptides. T helper cell responses to the peptides were evaluated by ELISpot (gamma-interferon) assay, using peripheral blood monocytes (PBMC) obtained from 34 healthy long term non-progressor (LT) or moderate-progressor (MP) donors (median years infected = 8.88, median CD4 T cells = 595, median VL = 1044). Nine peptides were tested, of which eight were confirmed in ELISpot assays using PBMC from the LT/MP subjects. These epitopes were ranked by Conservation and EpiMatrix score 1, 2, 3, 5, 7, 11, and 14 out of the set of 9 original peptides. Five of these peptides were selected for inclusion in an epitope-driven cross-clade HIV-1 vaccine (the GAIA vaccine). These data confirm the utility of bioinformatics tools to select and construct novel "immunogenic consensus sequence" T cell epitopes for a globally relevant vaccine against HIV.

AIDS Vaccines↗
PubMed2003

Directly observed antiretroviral therapy to reduce genital tract and plasma HIV-1 RNA in women with poor adherence.

Six women with substance abuse and poor adherence histories received daily antiretroviral directly observed therapy (DOT). Cervicovaginal lavage (CVL) and plasma HIV-1-RNA levels were measured at baseline, 1 month, 3 months, and 6 months. All subjects had undetectable (below 2.6 log10 copies/ml) CVL HIV-1-RNA levels by 3 months and undetectable plasma HIV-1-RNA levels by 6 months. The mean CD4 cell increase was 76 cells/mm3. DOT appears effective and may reduce infectiousness in this high-risk population.

Anti-HIV Agents↗
PubMed2003

Clinical and immunologic progression in HIV-infected US women before and after the introduction of highly active antiretroviral therapy.

OBJECTIVE: To examine factors associated with clinical and immunologic HIV disease progression in a cohort of US women. DESIGN: Analysis of data from a prospective, longitudinal, case-control study of HIV-infected women followed every 6 months for 7 years. SETTING: Four urban clinical centers in the United States. PARTICIPANTS: 648 HIV-infected women who did not have AIDS at time of entry into the study. MEASUREMENTS: Structured clinical and behavioral interviews; protocol-directed physical examinations; CD4 lymphocyte counts; plasma HIV RNA; infectious pathogen serologies. RESULTS With 2304 women-years of follow-up, 46.1% of the women developed AIDS; however, 93.3% of the diagnoses were based on CD4 counts dropping to <200 cells/mm(3). Only 10.6% of the women with CD4 counts <200 cells/mm(3) developed an opportunistic infection. Baseline CD4 count was the strongest predictor of subsequent clinical progression. Illicit substance use, multiple pregnancies, demographic variables, and other infections were not associated with progression. Among women with CD4 counts >500 cells/mm(3) at baseline, those who were anemic or had hepatitis C were more likely to progress to AIDS. By the end of the study, only 52% of the participants were on highly active antiretroviral therapy (HAART). CONCLUSIONS: Despite underutilization of HAART in this multicenter cohort of urban women, opportunistic infections were uncommon, despite CD4 declines.

AIDS-Related Opportunistic Infections↗
PubMed2003

Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women.

BACKGROUND: Data on the incidence and prognostic significance of renal dysfunction in HIV disease are limited. OBJECTIVE: To determine the incidence of proteinuria and elevated serum creatinine in HIV-positive and HIV-negative women and to determine whether these abnormalities are predictors of mortality or associated with causes of death listed on the death certificate in HIV-positive women. DESIGN: The incidence of proteinuria or elevated serum creatinine and mortality was assessed in a cohort of 885 HIV-positive women and 425 at-risk HIV-negative women. SETTING: Women from the general community or HIV care clinics in four urban locations in the United States. OUTCOME MEASURES: Creatinine of >or=1.4 mg/dL, proteinuria 2 or more, or both. Deaths confirmed by a death certificate (92%) or medical record/community report (8%). RESULTS: At baseline, 64 (7.2%) HIV-positive women and 10 (2.4%) HIV-negative women had proteinuria or elevated creatinine. An additional 128 (14%) HIV-positive women and 18 (4%) HIV-negative women developed these abnormalities over the next (mean) 21 months. Relative hazards of mortality were significantly increased (adjusted relative hazard = 2.5; 95% confidence interval: 1.9-3.3), and there were more renal causes recorded on death certificates (24/92 (26%) vs. 3/127 (2.7%), p<.0001) in HIV-infected women with, compared with those without these renal abnormalities. CONCLUSIONS: Proteinuria, elevated serum creatinine, or both frequently occurred in these HIV-infected women. These renal abnormalities in HIV-infected women are associated with an increased risk of death after controlling for other risk factors and with an increased likelihood of having renal causes listed on the death certificate. The recognition and management of proteinuria and elevated serum creatinine should be a priority for HIV-infected persons.

AIDS-Associated Nephropathy↗
PubMed2002

Total lymphocyte count (TLC) is a useful tool for the timing of opportunistic infection prophylaxis in India and other resource-constrained countries.

BACKGROUND: In most resource-constrained countries, CD4 cell count testing is prohibitively expensive for routine clinical use and is not widely available. As a result, physicians are often required to make decisions about opportunistic infection (OI) chemoprophylaxis without a laboratory evaluation of HIV stage and level of immunosuppression. OBJECTIVES To evaluate the correlation of total lymphocyte count (TLC), an inexpensive and widely available parameter, to CD4 count. To determine a range of TLC cutoffs for the initiation of OI prophylaxis that is appropriate for resource-constrained settings. METHODS: Spearman correlation between CD4 count and TLC was assessed in patients attending an HIV/AIDS clinic in South India. Positive predictive value (PPV), negative predictive value (NPV), and sensitivity and specificity of various TLC cutoffs were computed for CD4 count <200 cells/mm3 and <350 cells/mm3. Correlation and statistical indices computed for all patients and for patients dually infected with HIV and active tuberculosis. RESULTS: High degree of correlation was noted between 650 paired CD4 and TLC counts (r = 0.744). TLC <1400 cells/mm3 had a 76% PPV, 86% NPV, and was 73% sensitive, 88% specific for CD4 count <200 cells/mm3. TLC <1700 cells/mm3 had a 86% PPV, 69% NPV, and was 70% sensitive, 86% specific for CD4 count <350 cells/mm3. The cost of a single CD4 count in India is approximately 30 US dollars, whereas the cost of a single TLC is 0.80 US dollars. CONCLUSION: TLC could serve as a low-cost tool for determining both a patient's risk of OI and when to initiate prophylaxis in resource-constrained settings. PPV, NPV, sensitivity, and specificity maximally aggregated at TLC <1400 cells/mm3 for CD4 <200 cell/mm3 and TLC <1700 cells/mm3 for CD4 <350 cells/mm3. Selection of appropriate TLC cutoffs for prophylaxis administration should be made on a regional basis depending on OI incidence, antimicrobial resistance patterns, and availability of the antimicrobials.

AIDS-Related Opportunistic Infections↗
PubMed2002

Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel.

OBJECTIVE: New information warrants updated recommendations for the 4 central issues in antiretroviral therapy: when to start, what drugs to start with, when to change, and what to change to. These updated recommendations are intended to guide practicing physicians actively involved in human immunodeficiency virus (HIV)- and acquired immunodeficiency syndrome (AIDS)-related care. PARTICIPANTS: In 1995, physicians with specific expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care were invited by the International AIDS Society-USA to serve on a volunteer panel. In 1999, others were invited to broaden international representation. The 17-member panel met regularly in closed meetings between its last report in 2000 and April 2002 to review current data. The effort was sponsored and funded by the International AIDS Society-USA, a not-for-profit physician education organization. EVIDENCE AND CONSENSUS PROCESS: The full panel was convened in late 2000 and assigned 7 section committees. A section writer and 3 to 5 section committee members (each panel member served on numerous sections) identified relevant evidence and prepared draft recommendations. Basic science, clinical research, and epidemiologic data from the published literature and abstracts from recent (within 2 years) scientific conferences were considered by strength of evidence. Extrapolations from basic science data and expert opinion of the panel members were included as evidence. Draft sections were combined and circulated to the entire panel and discussed in a series of full-panel conference calls until consensus was reached. Final recommendations represent full consensus agreement of the panel. CONCLUSIONS: Because of increased awareness of the activity and toxicity of current drugs, the threshold for initiation of therapy has shifted to a later time in the course of HIV disease. However, the optimal time to initiate therapy remains imprecisely defined. Availability of new drugs has broadened options for therapy initiation and management of treatment failure, which remains a difficult challenge.

Adjuvants, Immunologic↗
PubMedDate not supplied

Racial differences in serum lipids in HIV+ women treated with protease inhibitor regimens.

PURPOSE: To evaluate cardiovascular risk factors in Caucasian and African American HIV+ women undergoing treatment with HAART including a protease inhibitor (PI). METHOD: Anthropometric measures and fasting blood samples were obtained from 32 Caucasian and 10 African American women. Serum was analyzed for glucose, insulin, and lipid levels. RESULTS: The African American women were significantly older than the Caucasian women. Body mass index (BMI) was higher in the African American women, and 80% of the African American women and 47% of the Caucasian women were overweight. There were no significant differences in fasting insulin, fasting glucose, or HOMA-IR. However, African American women had significantly higher HDL levels, whereas Caucasian women had higher triglycerides and LDL. When age-matched women were compared, total as well as LDL cholesterol was significantly higher in the Caucasian women. The ratio of total cholesterol/HDL cholesterol was 3.4 +/- 1.1 in the African American women and 5.5 +/- 1.6 (p=.021) in the age-matched Caucasian women. CONCLUSION: The differences in lipid levels in HIV+ African American and Caucasian women were greater than those reported in the literature for normal women. Although the sample size is small, the data suggest that the effect of HIV infection and/or HAART on lipid levels may be different in Caucasian and African American women. Large-scale studies will be necessary to confirm these results and clarify the mechanisms involved.

Adult↗