PRINTABLE PAGE

Research Developments in HIV/AIDS

Kiren Mitruka, MD; Brian Boyle, MD
Originally published in AIDS Reader 12(1):12-16, 2002

Introduction

Although at times barely audible to the clinicians who spend busy days caring for HIV-infected patients, the steady drumbeat of progress continues in HIV research. In the past few months, the beat has grown significantly faster and louder, with several important conferences providing new, valuable information regarding the evaluation and treatment of HIV infection and conditions associated with it. This information provides support for the important, and sometimes conflicting, concepts that HAART is extremely effective at controlling HIV and extending the lives of HIV-infected patients but that we must be cautious regarding its use and maintain a watchful eye for the emergence of virologic failure and resistance and for signs and symptoms of potential toxicities. In addition, while we continue to aggressively and effectively treat HIV, we must also remain concerned about other conditions, especially chronic hepatitis C virus and hepatitis B virus infections, that afflict our patients and that may also require antiviral therapy.

This column will provide a brief review of notable studies presented at several conferences over the past few months. We have decided to focus on a few key areas of concern to clinicians. Space requirements limit the extent of the coverage; however, additional information can be obtained from online sites, such as www.medscape.com, www.thebody.com, and www.hivandhepatitis.com.

Drug Resistance

In a study that used a mathematic model to understand and predict the increase in drug-resistant strains in San Francisco from 1996 to 2005, Blower and colleagues1 provided an interesting perspective on the epidemiology of drug resistance. Their objective was to identify the prevalence and transmissibility of drug-resistant strains and predict the relationship of these parameters in the future. They evaluated the relative fitness of 1000 different drug-resistant strains, defined by their transmission potential compared with that of drug-sensitive strains. The authors determined that the vast majority of new drug-resistant cases each year are likely to be due to the conversion of a strain from drug-sensitive to drug-resistant, rather than due to the transmission of drug-resistant strains. Their calculations indicated that the current prevalence of drug resistance is 29% and that this prevalence will continue to increase in the coming years. However, based on their model, the transmission rate of drug resistance is low and will remain low. In the year 2000, 8% of new cases of drug-resistant strains were due to transmission. The authors concluded that the transmission of drug-sensitive strains is a larger public health issue in San Francisco than is the transmission of drug-resistant strains—a finding that also may have implications for developing countries.

Contributing to the concern regarding drug resistance is the issue of low-level viremia that has been found in HIV-infected patients who receive HAART and have an undetectable viral load (below 50 copies/mL). Whether this low-level viremia is a reflection of the development of drug resistance was addressed in a study by Persaud and colleagues.2 These investigators developed a novel method to perform a genotype analysis on patients with viral loads below 50 copies/mL. This technologic advance was used to genotype the HIV-1 in the plasma of patients receiving prolonged HAART who had achieved and maintained a viral load below 50 copies/mL. From a cohort of 20 patients, they amplified 47 independent clones from 10 patients and found a "static and archival pattern" of drug resistance. They found that the virus detected did not have any genotypic mutations as a result of the current HAART regimen and that it was either wild-type or showed resistance mutations to HAART regimens the patient may have previously received. Phylogenetic analysis of HIV-1 pol sequences of virus from CD4+ T cells confirmed that the plasma-derived HIV was patient-specific. Thus, the results of this study support a static rather than a dynamic model of HIV-1 persistence, something that Dr Robert Siliciano from Johns Hopkins has proposed in the past, and the researchers concluded that low-level viremia in suppressed patients is not the result of drug resistance and that in patients with viral loads below 50 copies/mL, drug resistance mutations appear slowly or not at all.

The potential for the presence of dual infection with genetically different HIV-1 in the plasma and the genital tract has had important implications in HIV transmission and in responsiveness to therapies. Weiser and colleagues3 demonstrated that in some female patients, the reservoir of HIV-1 in the genital tract is genetically different from that in the plasma. The researchers studied the pol gene of HIV-1 from serial and paired plasma and genital tract samples from antiretroviral-experienced wom-en in the Women's Interagency Health Study. Five of these women had both parenteral and sexual exposure to HIV. Phylogenetic analysis as well as sequence analysis showed that the 2 compartments (plasma and genital tract) had large differences in their HIV-1 strain and even implied dual infection with different viruses in 3 of 10 women. Response to antiviral therapy also differed in the 2 compartments, with the HIV-1 in the genital tract being more responsive to HAART and with acquisition of fewer resistance mutations.

Adherence and Directly Observed Therapy

The role of directly observed therapy (DOT) in ensuring adherence to tuberculosis and HIV medications has been established in several studies. Mitty and colleagues4 from Brown University explored the effectiveness of DOT in improving adherence to HAART in HIV-positive patients with continuing substance abuse problems. The 22 HIV-positive patients selected for this study were active substance users, had a history of nonadherence, and were receiving HAART. The HAART regimens included combinations of the nucleoside reverse transcriptase inhibitors stavudine, didanosine, and lamivudine with a nonnucleoside reverse transcriptase inhibitor—either nevirapine or efavirenz—or ritonavir and saquinavir. An outreach worker met with the participants daily and observed the intake of therapy for 6 months. At 3 and 6 months, 77% and 50% of the patients, respectively, continued in the program. Viral load data showed that 44% of patients at 3 months and 70% of patients remaining in the study at 6 months achieved a viral load below 50 copies/mL. In this study, DOT was shown to be a feasible option to increase adherence among active substance abusers—a group shown, in some studies, to have poor adherence and high rates of virologic failure. The dropout rate of 50% at 6 months is quite high and disturbing, however, and large-scale studies with long-term outcomes need to be assessed.

Whether DOT for HAART (DOT-HAART) is cost-effective was explored by Fisman and colleagues5 using a mathematic model. They found that in a base-case simulation of 20,000 pregnant, asymptomatic, HIV-positive women in their third trimester, standard HAART based on the guidelines of the US Public Health Service would result in a 5% rate of peripartum transmission, with an average medical cost of $13,800. DOT-HAART decreased the transmission rate to 1.2% and the medical cost to $10,600. Subgroup analysis showed DOT-HAART provided health and economic benefit only to those patients with a viral load greater than 1000 copies/mL. In women with a viral load of 1000 to 10,000 copies/mL, DOT-HAART resulted in a gain of $5700 per quality-adjusted life year.

In several studies, DOT for patients receiving HAART has shown promise in improving outcomes in HIV-infected patients. The studies discussed above reinforce these findings. The study by Fisman and colleagues5 indicates that DOT may actually be a cost-effective means to increase adherence, especially in the most nonadherent patient populations. The difficulty, however, is in implementing DOT, especially in the patients who need it the most—those with an active substance abuse problem and/or psychiatric disease. We hope that future studies, including ongoing pilot DOT programs, will provide more information regarding this potentially valuable approach to therapy.

Opportunistic Infections

In the last 10 years, HAART has significantly changed the clinical spectrum of HIV disease as a result of its impact on the incidence of opportunistic infections (OIs) and their resulting morbidity and mortality.

McNaghten and colleagues6 at the CDC assessed the rates of OIs in a large cohort of 20,455 patients receiving HIV care in 11 US cities from 1995 to 1999. They determined that the rate of OIs declined during that time. However, there has been a leveling in the rate of OIs between 1998 and 1999, with a less significant decline than in the previous years. With the exception of a decrease in the incidence of CNS toxoplasmosis and cytomegalovirus (CMV) retinitis in men, no significant change was noted in the incidence of 26 OIs examined in either gender. This may have implications regarding other factors—such as adherence and resistant HIV strains—that may negate some of the initially observed positive effect of HAART on the incidence of OIs in the mid-1990s. Several abstracts presented new information relating to novel methods of diagnosing OIs. S-adenosylmethionine (AdoMet), a critical biochemical intermediate and a precursor in polyamine synthesis, was assessed as a marker for Pneumocystis carinii—the only known auxotroph of AdoMet.7 AdoMet levels were measured in 15 patients within 24 hours of the start of treatment for P carinii pneumonia (PCP) and compared with the levels in patients with asymptomatic HIV infection, bacterial pneumonia, cryptococcosis, and tuberculosis. The AdoMet levels were found to be significantly depressed in patients who had PCP and were noted to rise with therapy. AdoMet levels in patients with bacterial pneumonia were not depressed and did not change. Persistently low levels of AdoMet were found in patients with PCP who died, possibly implying treatment failure.

The utility of a CMV pp65 antigen test was also evaluated in the diagnosis of concomitant end-organ CMV disease in patients with HIV.8 Retrospective chart reviews of 266 HIV-positive patients who had CMV antigen tests were conducted. A diagnosis of CMV in these patients was based on histopathologic findings, except in cases of retinitis. Concomitant disease was defined as CMV end-organ disease within 30 days of the CMV antigen test. It was found that the CMV antigen test had a high negative predictive value (97%) but that it was relatively insensitive, with its highest positive predictive value (60%) when applied only to those patients with a high likelihood of CMV disease (ie, patients with a CD4+ T-cell count below 100/無 and symptoms suggestive of CMV disease).

Lactate dehydrogenase (LDH) as an adjunctive marker to distinguish between histoplasmosis and PCP was assessed in a retrospective case-controlled study of 150 patients in New Orleans.9 It was found that serum levels of LDH greater than 600 U/L were suggestive of histoplasmosis rather than PCP (odds ratio, 9.41; 95% CI, 3.43, 26.31; P < .01), with a sensitivity of 50% and specificity of 89%.

The efficacy, value, and cost-effectiveness of performing anal Papanicolaou (Pap) smears for the early detection of human papillomavirus-associated anal lesions and carcinoma in HIV-positive men have not been established.10 A large-scale study of 397 HIV-positive men, of whom 60% were men who have sex with men (MSM), was carried out in a community-based HIV clinic. The histopathology of 522 anal Pap smears collected during a 2-year period was reviewed and correlated with clinical outcome. The total number of normal smears was 63%; 22% were inadequate and 15% were abnormal (squamous atypia or low-, moderate-, or high-grade dysplasia). The abnormal Pap smear led to treatment of benign lesions (condylomata or anal warts) in 3.5% of patients and to the treatment of precancerous or cancerous lesions in 1% of patients. There was a large loss of patient follow-up, limiting the full assessment of the clinical significance of performing anal Pap smears. However, the authors felt that anal Pap smears were both practical and well accepted by patients and a more clear benefit from them could be demonstrated by reducing the number of inadequate smears and ensuring follow-up.

Epidemiology

Several studies focused on survival trends since the advent of HAART. Nash and colleagues11 used proportional hazard modeling from time of diagnosis to death for a cohort of HIV-positive patients between 1993 and 1999 to identify predictors of mortality before and after widespread availability of HAART in New York City. Cohort-specific multivariate models were developed by adjusting for variables such as age, sex, borough of residence, HIV-transmission risk category, and time since diagnosis to the beginning of each calendar year. The researchers found that since 1996, disparities in mortality rates have widened between older and younger persons (relative risk [RR] 1995, 1.7; 95% CI, 1.5 to 2 versus RR 1998, 2.9; 95% CI, 2 to 4.1). Similar differences in mortality trends are evolving between injection drug users and MSM populations, with injection drug users having a higher mortality rate than MSM since 1996 (RR 1995, 1.4; 95% CI 1.3 to 1.7 versus RR 1999, 1.9; 95% CI,1.5 to 2.3). The authors point out that these disparities in mortality rates may reflect differences in access to and use of HAART in the different groups and may call for targeted interventions and therapy.

A study of the impact of HIV care and sociodemographic characteristics on survival trends in HIV-positive patients was performed at the University of California, San Diego, Owen Clinic during 1990 to 1999.12 This study found that mortality rates declined markedly from 1990 to 1996 but then became stable or rose slightly thereafter (1990, 68%; 1996, 16.4%; 1998, 17.8%). Controlling for CD4+ T-cell counts and plasma viral load and stratifying on year of entry showed that those at greatest risk for death had the following characteristics: male gender (hazard ratio [HR], 1.8), older age (HR, 1.1 per 10-year increment), injection drug use (reference MSM-HR, 1.3), and African American ethnicity (HR versus whites, 1.3).

These studies show that to continue the downward trend in HIV-related mortality, certain populations will need greater attention to improve their choices regarding, and acceptance of, therapy and their adherence to that therapy. Making a significant impact on these difficult-to-treat populations may require that clinicians carefully focus the approach to therapy to take into account the unique characteristics and needs of each population.

Antiretroviral Therapy Studies

*Atazanavir: an effective protease inhibitor (PI) with fewer lipid problems.

In a study presented at the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection (ECCATHI) meeting (AI424-008) comparing atazanavir-based HAART with a regimen containing nelfinavir, 467 antiretroviral-naive patients were randomized to receive 400 or 600 mg of atazanavir once daily or open-label nelfinavir at 1250 mg twice daily in combination with stavudine and lamivudine.13 In patients who completed the treatment through 48 weeks, the proportions with a viral load below 400 copies/mL were 74%, 75%, and 60% in the 400-mg atazanavir, 600-mg atazanavir, and nelfinavir arms, respectively (P < .05); however, there was no difference in patients who had less than 50 copies/mL, 41%, 42%, and 39%, respectively. Increases in CD4+ T-cell counts were in the 200/無 range and were relatively comparable among the regimens. While the regimens were relatively comparable regarding virologic and immunologic outcomes, patients treated with atazanavir had superior lipid profiles at 48 weeks with significantly lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels than those in the nelfinavir arm. Adverse events in this trial included infection and headache, with similar numbers of incidences in the atazanavir and nelfinavir arms. The nelfinavir arm had a higher incidence of diarrhea (56%) than the 400-mg (20%) and 600-mg (15%) atazanavir arms. Grade 4 hyperbilirubinemia was an uncommon adverse event, occurring in fewer than 2% of patients in the 600-mg atazanavir arm, and was managed by dose reduction.

*Saquinavir-ritonavir effective in PI-experienced patients.

In the Fortovase Genotyping Surveillance Program (Fortogene) trial, Spanish researchers evaluated the efficacy and safety of combination treatment with saquinavir-ritonavir among 144 heavily pretreated—but saquinavir-naive—HIV-positive patients with a mean viral load of 100,047 copies/mL and a mean CD4+ T-cell count of 367/無.14 The investigators also evaluated the utility of genotypic testing and drug level measurement in predicting virologic response. They examined data on 102 patients after the patients had completed 24 weeks of combination treatment that included 1000 mg of saquinavir plus 100 mg of ritonavir. Seventy-six patients (75%) experienced a greater than 1 log10 copies/mL decline in viral load, and 61 patients (60%) achieved a viral load below 50 copies/mL. In the multivariate analysis, both genotypic testing and measurement of drug levels were predictive of a favorable response to therapy.

*Once-daily therapy with efavirenz-based HAART.

In ANRS 091—an open-label pilot study that enrolled 40 antiretroviral-naive patients who were treated with efavirenz plus didanosine EC plus emtricitabine—34 (85%) of 40 patients maintained a viral load below 400 copies/mL, and 32 (80%) of 40 had a viral load below 50 copies/mL at 96 weeks.15 In addition, 8 (89%) of 9 patients with a baseline viral load greater than 100,000 copies/mL achieved a viral load below 400 copies/mL at 96 weeks. The median increase in CD4 cell count observed at week 96 was 272/無. The most common treatment-related adverse events occurred during the first 24 weeks of the study and consisted of mild to moderate CNS symptoms in 73% of patients, diarrhea in 37%, and rashes in 10%. There were 22 serious adverse events reported in 16 patients, 4 of which were possibly treatment-related. Only 3 patients discontinued treatment because of an adverse event.

*Efavirenz-based HAART superior to nevirapine-based HAART in a cohort study.

A HAART regimen containing efavirenz appears to be superior to nevirapine in treatment-naive patients, according to results of another study presented at the 8th ECCATHI.16 In this study, involving a cohort of 1078 antiretroviral-naive patients, those treated with a regimen containing efavirenz experienced lower rates of treatment failure (37.1%) over a longer duration of time compared with a regimen containing nevirapine (59.4%) (P < .001). This study also demonstrated a shorter time to treatment failure (307 days) in the nevirapine arm than in the efavirenz arm (589 days). These data are consistent with data from 2 other recently presented cohort studies, which also found efavirenz to be superior to nevirapine.17,18

*Kaletra highly effective in antiretroviral-naive patients.

M97-720, a phase 2, double-blind trial of lopinavir-ritonavir (Kaletra), stavudine, and lamivudine in antiretroviral-naive patients, was the first trial of Kaletra and provides the longest duration of follow-up.19 Under an on-treatment and intent-to-treat analysis at 156 weeks of therapy, 99% and 75% of patients, respectively, achieved a viral load below 400 copies/mL, and 96% and 76%, respectively, below 50 copies/mL. The mean CD4 cell count increased 356/無. Kaletra was well tolerated, with only 5 (5%) of the 100 enrolled patients discontinuing therapy as a result of a Kaletra-related adverse event. The most common adverse events and grade 3 to 4 laboratory abnormalities were diarrhea (25%), nausea (16%), cholesterol level above 300 mg/dL (17%), and triglyceride level above 750 mg/dL (16%).

*Tenofovir-drug interactions.

Studies presented at the 8th ECCATHI provided information regarding potential drug-drug interactions with tenofovir.20,21 Tenofovir pharmacokinetics were unaffected by lamivudine and efavirenz, while indinavir increased the maximum inhibitory concentration (Cmax) (14%) of tenofovir without affecting the area under the curve (AUC), and Kaletra moderately increased both the Cmax (30%) and AUC of tenofovir. None of these changes was considered clinically significant. Tenofovir was not found to have any interaction with efavirenz; however, it was found to cause a slight delay in the time to maximal concentration of lamivudine and a decrease (24%) in the Cmax of lamivudine without altering the AUC; a lowered Cmax of indinavir (11%) without a change in AUC; a lowered Cmax and AUC (15%) for Kaletra, while maintaining the Kaletra minimum inhibitory concentration and inhibitory quotient; and an increase in the AUC and Cmax of didanosine by 40% and 28%, respectively. With the exception of the tenofovir and didanosine interaction, none of the changes appear to be clinically significant. There were no significant adverse events associated with the combination of tenofovir with any of the studied drugs. And so the acquisition of knowledge and the improvement in therapeutic options for HIV-infected patients continues. While we continue to confront morbidity and mortality in our patients, and while there are many challenges ahead, we can take heart in the progress we have made—and in the lives that have been, and will be, saved.

References

  1. Blower S, Aschenbach AN, Gershengorn HB, Kahn JO. Predicting the unpredictable: the transmission of drug resistant HIV. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 655.
  2. Persaud D, Hermankova M, Ruff C, et al. Arresting HIV-1 evolution with highly active antiretroviral therapy (HAART). In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 778.
  3. Weiser B, Burger H, Chappey C, et al. HIV-1 in plasma and genital tract of women: dual infection and drug resistance in different compartments. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 782.
  4. Mitty JA, Macalino GE, McKenzie M, et al. Directly observed therapy (DOT) among HIV seropositive substance users: a pilot study. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 707.
  5. Fisman D, Cosgrove SE, Perencevich EN, et al. Cost-effectiveness of directly observed highly active antiretroviral therapy in pregnant women with asymptomatic HIV infection. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 794.
  6. McNaghten AD, Hanson DL, Nakashima AK, Swerdlow DL. Incidence of AIDS-defining opportunistic illnesses in the US may be leveling form 1998 to 1999. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 751.
  7. Skelly M, Hoffman J, Fabbri M, et al. Changes in S-adenosylmethionine levels in the course of treatment of human Pneumocystis carinii pneumonia (PCP): a potential aid in rapid diagnosis In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 19.
  8. Skiest DJ, Crosby C. CMV pp65 is of limited utility in the diagnosis of concomitant CMV disease in HIV+ patients. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 771.
  9. Butt AA, Michels S, Greer D, et al. Serum LDH level as a clue to the diagnosis of histoplasmosis. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 773.
  10. Fine SM, Corales RB, Christie ML, et al. Anal Pap smears in 397 HIV+ men at a community based clinic. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 763.
  11. Nash D, Lee LM, Sackoff J, et al. Predictors of mortality among persons living with acquired immunodeficiency syndrome before and after the widespread availability of highly active antiretroviral therapy—New York City, 1993-1999. In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 17.
  12. Mathews WC, Barber RE. Outcomes of HIV care: survival trends and variation after entering care at UCSD Owen Clinic (1990 - 1999). In: Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco. Abstract 728.
  13. Pantaleo G, Sanne I, Cahn P, et al. Atazanavir (BMS-232632): 48-week safety and efficacy vs nelfinavir, each in combination with stavudine and lamivudine, in treatment-naive, HIV-positive subjects (AI424-008). In: Program and abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; October 28-31, 2001; Athens, Greece. Abstract 223; Oral presentation 11.
  14. Carosi G, Moroni M, Angarano G, et al. Fortogene program: saquinavir sensitivity in Italian experienced HIV+ patients. In: Program and abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; October 28-31, 2001; Athens, Greece. Abstract 251.
  15. Molina JM, Ferchal F, Journot V, et al. Once-daily combination therapy with emtricitabine, didanosine and efavirenz in treatment naive HIV-infected adults: 96-week follow-up of the ANRS 091 trial. In: Program and abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; October 28-31, 2001; Athens, Greece. Abstract 221.
  16. Keiser P, Nassar N, Visnegarwala F, White C. Comparison of efavirenz containing regimens to nevirapine containing regimens in anti-retroviral naive HIV infected patients: a cohort study. In: Program and abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; October 28-31, 2001; Athens, Greece. Late Breaker 22.
  17. Philips AN, Pradier C, Lazzarin A, et al. Virological and clinical outcome of NNRTI-containing regimens for 1932 patients in EuroSIDA. In: Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago. Abstract 324.
  18. Matthews GV, Sabin SA, Mandalia S, et al. Comparison of first-line antiretroviral therapy success in a cohort analysis of over 1000 patients (protease inhibitor vs non-nucleoside reverse transcriptase inhibitor). In: Program and abstracts of the 7th Annual Conference of the British HIV Association; April 27-29, 2001; Brighton, England. Abstract 03.
  19. Thompson M, Brun S, King M, et al. Kaletra (lopinavir/ritonavir) in antiretroviral-naive HIV+ patients: 3 year follow up. In: Program and abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; October 28-31, 2001; Athens, Greece. Abstract 225.
  20. Kearney BP, Flaherty J, Wolf J, et al. Lack of clinically relevant drug-drug interactions between tenofovir DF and efavirenz, indinavir, lamivudine and lopinavir/ritonavir in healthy subjects. In: Program and abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; October 28-31, 2001; Athens, Greece. Abstract 171.
  21. Kearney BP, Flaherty J, Wolf J, et al. Coadministration of tenofovir DF and didanosine: pharmacokinetic drug-drug interaction and safety evaluations. In: Program and abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; October 28-31, 2001; Athens, Greece. Abstract 172.

Dr. Mitruka is a fellow and Dr. Boyle is assistant attending physician and assistant professor of medicine in the department of international medicine and infectious disease, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York.

Copyright © 2002 Cliggott Publishing, Division of SCP Communications.