The recent approval of two fixed-dose coformulated nucleoside analog reverse transcriptase inhibitor (NRTI) combinations, Truvada (tenofovir DF + emtricitabine) and Epzicom (abacavir + lamivudine), has probably succeeded in narrowing rather than expanding options for initial therapy in treatment-naïve individuals. There is now little reason to start therapy with an NRTI backbone other than Combivir or one of these two newer fixed dose combinations (FDCs).
HIV is primarily thought of as a young person’s disease; however, the prevalence of HIV infection in people over the age of 50 years is growing. The reasons for this change include increased longevity due to HAART as well as a growing number of older patients becoming infected with HIV through high risk exposures. The number of AIDS cases reported in adults 50 years and over quintupled between 1990 and 2001 from 16,288 to 90,513. As a result, the number of HIV-infected persons over 65 years has grown 10-fold in the past 10 years.
Department of Health and Human Services Guidelines for the Treatment of Opportunistic Infections have been approved by the guidelines committee; they are in press at the MMWR and will available at http://AIDSInfo.nih.gov. These guidelines are a supplement to the existing OI prevention guidelines (2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with HIV - November 28, 2001).
Those of us attending the "Track B" clinical sessions couldn't help but feel that we were on the sidelines, missing out on the real "action" of the conference. That is, the politics, the epidemiology, and the discussions of treatment delivery in the developing world: what's working, what's not, and what remains to be done.
Adriana Andrade, M.D., M.P.H. and Charles Flexner, M.D.
During the 11th CROI in San Francisco, two studies investigated a possible role for genetic differences as the basis for developing EFV toxicity. Both abstracts presented data from Adult AIDS Clinical Trials Group (AACTG) Protocols 5095/5097, in which HIV-infected antiretroviral-naïve subjects were randomized to receive either efavirenz (EFV) plus zidovudine/lamivudine/abacavir (Trizivir) or Trizivir alone.
The 11th CROI was marked by two "firsts": It was the first time CROI was blessed with glorious weather, and it was the first time that many of the more clinically focused participants felt they were walking away somewhat empty-handed. There were certainly important basic science data presented, as well as some compelling data on drug resistance, prevention of mother-to-child transmission, and treatment of HIV/HCV coinfection. But for the most part, the large randomized trials of antiretroviral therapy either were not submitted, were not accepted, or were relegated to poster sessions.
In summary, many metabolic complications have been found to be more common in HIV-infected persons, although the data do not consistently support that that these manifestations are directly related to antiretroviral therapy. However, antiretroviral toxicity may contribute to cumulative or additive risk of developing a complication. In addition to considering an agent's potency and durability, careful consideration must be given to factors that may place a patient at increased risk of a complication. Harris' study is an excellent reminder that we should always consider estimated creatinine clearance before for any agent that is cleared through the kidney.
Joel N. Blankson M.D., Ph.D. and Joel E. Gallant, M.D., M.P.H.
Many studies have shown that this response plays a key role in helping cytotoxic T-lymphocytes control viral infections [Reviewed by Kaech and Ahmed, Science 2003;300:263]. Thus treatment during primary infection, followed by therapeutic vaccination when available, may be a viable strategy for improving long-term immune control of viral replication.
conclusion, while encouraging treatment data were presented at CROI, including data suggesting improved sustained virologic responses with the new PEG-INFs, the reality of more liver-related deaths, and the lack of progress in HCV vaccine development was sobering.
A number of abstracts at the 11th CROI meeting focused on long-term complications of HIV treatment. Although there were excellent basic science reports, I will focus here on the clinical studies.
Deborah Persaud, M.D. and Joel E. Gallant, M.D., M.P.H.
These results are not particularly surprising given what we know about NNRTI pharmacokinetics and the permanent nature of drug resistance. The conservative assumption has always been that resistance is clinically relevant, regardless of whether it occurs in the setting of primary infection, HAART, or PMTCT. The implications for resource poor countries are less clear, however, since single dose NVP is a practical and cost-effective way to reduce perinatal transmission.
Forty-eight-week data from BMS 045 continued to show similar virologic efficacy of ATV/RTV and LPV/r in treatment experienced patients, with better lipid parameters in the former group. This suggests that boosting drug concentrations well above the viral IC50, reasonable dosing and pill burdens, and tolerability are the main factors currently driving the overall effectiveness of PI-based regimens. Adding ABC to IDV-based regimens was not associated with any durability benefit in patients with suppressed viral loads, and continuing 3TC in the presence of M184V was not associated with benefit in minimally to moderately antiretroviral-experienced patients initiating a salvage regimen. Finally, additional basic science and clinical research has shed light on the K65R resistance mutation and how its effects on NRTI incorporation and excision lead to different net effects for different drugs, particularly in combination with M184V.
Another revision of the DHHS "Guidelines for the Use of Antiretroviral Agents in HIV- 1-Infected Adults and Adolescents" was published, in draft form for public comment, on November 10, 2003. This represents a new style for the Guideline Panel, intended to address relevant issues in a more timely fashion and to permit "audience participation". This reflects the velocity of changes that take place in this field, which was forced, in part, by the introduction of 4 new antiretroviral agents in 2003.
Petros C. Karakousis, M.D., Kathleen R. Page, M.D., and William R. Bishai, M.D., Ph.D.
Paul A. Volberding, M.D., University of California at San Francisco and William G. Powderly, M.D., Washington University conducted a review of literature and conference presentations on the important new findings in HIV. The review was presented as part of “Symposium: What’s Hot: Review of Recent HIV and ID Literature” at the 41st IDSA meeting held in San Diego this fall and is summarized in this article.
The IDSA and the ACTG recently updated their guidelines for management of dyslipedemia, which were published as “Guidelines for the Evaluation and Management of Dyslipidemia in Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy: Recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group”
Since its availability in 1996, the use of highly active antiretroviral therapy (HAART) to treat HIV-infection has led to declines in U.S. AIDS mortality rates and increases in the number of persons living with HIV. For HIV-infected individuals, drug resistance is a major concern, but it is unknown whether resistance is an inevitable consequence of long-term HAART use. HAART can be inherently complex if it involves taking many pills at specific times or with food restrictions, or if it is associated with side effects.
Extensive analysis of the Boeringer-Ingelheim database by the company has indicated a high risk of hepatotoxicity in women with CD4 counts >250 cells/mm3 who have been treated with nevirapine.
This year marks the 20th anniversary of the Moore Clinic and the beginning of the Johns Hopkins AIDS Service. The Moore Clinic had it’s origins in 1915 as a clinic for the treatment of syphilis. Over the ensuing years the Moore Clinic served people with a variety of chronic and hereditary disorders. In January 1984, Dr. Frank Polk and Dr. John G. Bartlett set aside one half day a week in the Clinic to take care of a small group of gay men with AIDS. This was at a time when the viral origin of AIDS was only hypothesized and there was little medical intervention except treatment of opportunistic infections.
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