Nevirapine-associated hepatotoxicity was not predicted by CD4 count ≥250 cells/µL among women in Zambia, Thailand and Kenya.

OBJECTIVE: The aim of the study was to determine risk factors for developing severe hepatotoxicity (grade 3 or 4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥ grade 2 hepatotoxicity) among women initiating nevirapine-based antiretroviral therapy (ART). METHODS: The Non-Nucleoside Reverse Transcriptase Inhibitor Response Study was a prospective cohort study carried out in Zambia, Thailand and Kenya. Between May 2005 and January 2007, we enrolled antiretroviral-naïve HIV-infected women initiating nevirapine-based ART. At enrollment and at weeks 2, 4, 8, 16 and 24, participants had serum alanine transferase (ALT) and aspartate transaminase (AST) measured and were evaluated clinically for hepatitis and rash. RESULTS: Nevirapine-based ART was initiated in 820 women and baseline ALT or AST results were abnormal (≥ grade 1) in 113 (14%) women. After initiating nevirapine-based ART, severe hepatotoxicity occurred in 41 (5%) women and rash-associated hepatotoxicity occurred in 27 (3%) women. In a multivariate logistic regression model, severe hepatotoxicity and rash-associated hepatotoxicity were both associated with baseline abnormal (≥ grade 1) ALT or AST results, but not with a baseline CD4 cell count ≥250 cells/µL. Three participants (0.4%) died with symptoms suggestive of fatal hepatotoxicity; all three women had baseline CD4 count <100 cells/µL and were receiving anti-tuberculosis therapy. CONCLUSION: Among women taking nevirapine-based ART, severe hepatotoxicity and rash-associated hepatotoxicity were predicted by abnormal baseline ALT or AST results, but not by a CD4 count ≥250 cells/µL. In resource-limited settings where transaminase testing is available, testing should focus on early time-points and on women with abnormal baseline ALT or AST results.

The acceptability of a directly-administered antiretroviral therapy (DAART) intervention among patients in public HIV clinics in Los Angeles, California.

Directly administered antiretroviral therapy (DAART) is an intensive adherence support strategy for highly active antiretroviral therapy (HAART) that requires patient acceptance to be effective. In one arm of a randomized adherence study, community workers (CW) delivered and observed ingestion of one HAART dose to participants five days a week for six months. We evaluated acceptability by study participation, retention, attendance and a satisfaction survey. Chi-square and nonparametric tests were used to examine differences between participants who did and did not complete DAART. Between November 2001 and March 2004, 416 eligible participants were identified; 250 were enrolled and 166 refused to participate (22 of these (13%) because of DAART specifically). Of the 82 randomized to DAART (70% Latino, 20% African American, 27% female and 69% foreign-born), 65 (79%) completed six months of DAART. Participants attended 6,953/7,390 (94%) appointments. Latinos were more likely to complete DAART compared to African Americans (OR=4.76, 95%CI=1.38, 16.44, p=0.01). In addition, foreign-born participants were more likely to complete DAART than US-born participants (OR=3.38, 95%CI=1.11-10.22, p=0.03). Participants completing DAART reported high rates of satisfaction. Retention, attendance and participant satisfaction suggest that DAART is an acceptable adherence support strategy in this public clinic population, particularly among Latino and foreign-born participants.

Comparison of azathioprine and mycophenolate mofetil for the prevention of acute rejection in recipients of pancreas transplantation.

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events.

Resistance to antiretroviral therapy among patients in Uganda.

OBJECTIVE: To characterize HIV-1 phenotypic resistance patterns and genotypic mutations among patients taking antiretroviral medications in Uganda. METHODS: We reviewed charts and retrieved archived plasma specimens from patients at an AIDS specialty center in Uganda where antiretroviral therapy has been used since 1996. Phenotypic and genotypic resistance testing was done on specimens associated with a viral load of 1000 copies/ml. RESULTS: Resistance testing of specimens was completed for 16 patients. Among 11 specimens collected before initiation of antiretroviral therapy, no phenotypic resistance or primary genotypic mutations were found. Among 8 patients taking lamivudine, phenotypic resistance was found for 9 (90%) of 10 specimens and was associated with an M184V mutation in all nine cases. Among 12 patients taking zidovudine, no phenotypic resistance and few primary mutations were found. For 6 patients who were receiving protease inhibitors, we observed no phenotypic resistance and only one primary genotypic mutation associated with resistance. CONCLUSIONS: The absence of apparent resistance among samples collected before antiretroviral therapy supports the notion that a similar approach to selection of antiretroviral therapy can generally be used against non-B subtypes. A genotypic marker of antiretroviral resistance to lamivudine in HIV-1 subtypes A, C, and D was similar to those in subtype B infections. These results suggest that the methods used for monitoring for the emergence of drug resistance in antiretroviral programs in Africa may be similar to those used in developed settings.

Factors associated with the successful modification of antiretroviral therapy. HIV Outpatient Study Investigators.

OBJECTIVES: To assess the characteristics of medication regimen modification and the influence of a commercial genotypic resistance assay on the short-term (3-12 weeks) viral load response (> or = 0.5 log reduction) in HIV-1-infected patients extensively treated with antiretroviral therapy (ART). METHODS: A nested cohort study was performed in two clinics from the HIV Outpatient Study of 96 persons with a HIV-1 viral load of 10(4) log copies/ml or greater taking at least two antiretroviral medications. RESULTS: Successful modification was associated with adding at least two new medications [relative risk (RR), 1.5; 95% confidence interval (CI), 1.1-2.2], adding a drug from a previously unused class of agents (RR, 2.0; CI, 1.4-2.9), the initiation of a non-nucleoside reverse transcriptase inhibitor (NNRTI) (RR, 1.7; CI, 1.2-2.4), but not substituting a protease inhibitor or the use of a commercial genotypic resistance assay. CONCLUSION: Incorporating a drug from a previously unused class or changing at least two new medications, but, within the confines of this study, not using a commercial genotypic resistance assay, was associated with the successful modification of ART as measured by a reduction in viral load.

Presence of human immunodeficiency virus (HIV) type 1, group M, non-B subtypes, Bronx, New York: a sentinel site for monitoring HIV genetic diversity in the United States.

In the United States, human immunodeficiency virus (HIV) type 1, group M, subtype B is the predominant subtype. A cross-sectional study of HIV-infected patients at the Bronx-Lebanon Hospital Center, Bronx, NY, between September 1997 and February 1998 identified 3 (1. 2%) of 252 persons infected with non-B subtypes: subtypes A and F, 1 each, and 1 potential recombinant subtype B(env)/F(prt). All 3 persons were born in the United States and tested positive for HIV antibodies between 1988 and 1997 while living in the Bronx. None reported travel to other countries, receipt of blood products, or drug injection. This study is among the first to indicate probable transmission of non-B HIV-1 subtypes in the United States. The occurrence of non-B HIV-1 subtypes in long-term US residents without a history of foreign travel may have implications for the evaluation and development of antiretroviral drugs, vaccines, and tests intended for use in the United States to diagnose HIV infection and screen blood.

Adherence to antiretroviral medications in an inner-city population.

Adherence to antiretroviral medications is essential for optimal treatment of HIV infection. We investigated nonadherence to antiretroviral medications in an inner-city population by using a confidential interview and a self-administered anonymous questionnaire. We estimated adherence on the day before and the month before the interview and asked reasons for nonadherence. Of 173 people who were taking antiretroviral medications, all participated in the confidential interview and 101 also completed the anonymous questionnaire. Results of the confidential interview and the anonymous questionnaire revealed rates of 6% and 28%, respectively, for nonadherence to any drug on the preceding day and of 11% and 39%, respectively, in the preceding month. The most common reasons for nonadherence in both methods were forgetfulness, inaccessibility of medications, and perceived or actual toxicity. On 12% of the anonymous questionnaires one reason for nonadherence was perceived or actual lack of drug efficacy: this reason was not given in any of the confidential interviews. Responses about the extent of nonadherence and the reasons for it may differ depending on the method of ascertainment. Interventions to improve adherence should focus on making medication dosages easier to remember, ensuring a continued supply of medications, and circumventing toxicities.

Effect of pharmacist interventions on medication use and cost in hospitalized patients with or without HIV infection.

Pharmacotherapeutic interventions and drug acquisition costs in HIV-positive and HIV-negative patients on a hospital medical service were studied. In November and December 1995, HIV-positive and HIV-negative patients were randomly selected and matched on the basis of admission date. Pharmacotherapeutic interventions were recorded by a pharmacist until the time of discharge. Drug acquisition costs were obtained through records of medications ordered. The two patient groups were compared with respect to length of stay (LOS), number and cost of medications, and number of interventions. HIV-positive patients had significantly more medication orders and required more interventions than HIV-negative patients. Mean LOS was not significantly different. HIV status and number of medications were significantly associated with requiring five or more interventions. Drug acquisition costs were significantly higher in the HIV-positive group. The mean pharmacist-attributed cost saving per patient was $134 for HIV-positive patients and $27 for HIV-negative patients. HIV-positive patients required more interventions and consumed more medication resources than HIV-negative patients. Pharmacist interventions produced drug acquisition cost savings for both groups, with more savings being realized for positive patients.

Evaluating the cost of medications for ambulatory HIV-infected persons in association with landmark changes in antiretroviral therapy.

Costs of medications for ambulatory HIV-infected people increase as knowledge of antiretroviral therapy and therapy for opportunistic infection grows. We evaluated the evolution of drug costs for HIV-infected persons who attend a university clinic in Baltimore, Maryland. Cross-sectional abstracts of a cohort of patients for four periods, corresponding to landmark changes in therapy, who attended the clinic between June 1995 and September 1996 were obtained. Monthly medication costs for all patients were calculated. Mean costs increased significantly (p < .01) from period 1 ($447 U.S.) to period 4 ($1048 U.S.). Multivariate analysis only revealed higher costs for patients with a CD4+ count <200 cells/mm3 (p < .001). The proportion of costs attributable to antiretroviral therapy increased from 34% in period 1 to 53% in period 4. Combination therapy increased >10-fold, from 8% in period 1 to 94% in period 4. Protease inhibitor use also increased significantly, from 4% in period 2 to 53% in period 4. We quantified the increase in costs of medications from mid-1995 to late 1996. Increases in costs appear to be the result of increasing complexity of drug regimens, particularly antiretroviral therapy in combinations.

Systemic hypertension associated with cyclosporine: a review.

Use of the immunosuppressive agent cyclosporine has been associated with an increased incidence of hypertension. The incidence, onset, duration, and severity of the associated blood pressure elevation varies greatly depending on the therapeutic indication for cyclosporine use. This paper reviews the disparity in the reports of cyclosporine-associated hypertension and the factors evaluated for possible association. Possible mechanisms involved in the blood pressure elevation as well as treatment approaches that have been employed are discussed. Further research efforts are needed to clarify conflicting information regarding mechanisms, associated factors, and rational treatment.

Management of Pneumocystis carinii pneumonia in patients with AIDS and other conditions: experience in a Philadelphia University Teaching Hospital.

We reviewed the records of 49 patients who had 55 episodes of Pneumocystis carinii pneumonia (PCP) from January 1984 to January 1987. Thirty-three patients had acquired immunodeficiency syndrome (AIDS), with the risk groups being homosexual/bisexual practices (26), hemophilia (6), and blood transfusion (1). Fourteen patients had a history of malignancy or chemotherapy and two underwent organ transplantation. Overall response to therapy of PCP was 75% (77% of patients with AIDS, 68% of those with other conditions). All six relapses occurred in patients with AIDS. Both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine were associated with a higher rate of toxicity in those patients than in patients with other conditions. A 30% rate of failure due to side effects occurred when TMP-SMX was used as initial therapy, but the combination is considered effective and should be given an adequate therapeutic trial. Pentamidine was an effective alternative for patients who failed with TMP-SMX and for those who failed therapy due to side effects, but was associated with serious toxicities. Our experience was similar in some respects to previous published results from New York and California.