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5 December 2005
TMC125 is safe and effective in patients with NNRTI resistance
 
The new non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125 is safe, well-tolerated and effective in HIV-positive patients with NNRTI and protease inhibitor resistance, according to data from two studies presented last week at the Tenth European AIDS Conference / European AIDS Clinical Society in Dublin. This indicates that TMC125 could be the first NNRTI that can be used after the development of resistance to other members of this drug class.

The currently available NNRTIs efavirenz (Sustiva) and nevirapine (Viramune) are potent anti-HIV drugs that can reduce viral loads and increase CD4 cell counts when used in combination with other antiretroviral agents. However, a disadvantage of these drugs is that only one mutation is required for HIV to become resistant to them, and that resistance to one drug leads to resistance to both drugs, preventing either from being used in the future.

TMC125 or etravirine is under development by the Belgian pharmaceutical company Tibotec and was designed to be active against HIV with pre-existing resistance to other NNRTIs. Previous studies have shown that TMC125 taken alone can reduce viral loads in patients with NNRTI resistance mutations.

For the studies presented in Dublin, investigators from Tibotec wished to assess the safety and efficacy of TMC125 in combination with other antiretroviral drugs in patients with substantial HIV treatment experience.

Safety and tolerability

In TMC125-C203, the first of two studies presented, the researchers randomised 240 patients to receive TMC125 at a dose of 400, 800 or 1200mg twice daily, or to receive placebo. TMC125 or the dummy pills were taken alongside an optimised background regimen consisting of at least two active antiretroviral drugs, which were chosen for each patient individually.

All of the patients had taken at least one drug from the three major classes of anti-HIV drugs for three months or more and were failing their current treatment regimen with viral loads above 1000 copies/ml.

The study was double blind, meaning that neither the patients nor the investigators knew which dose of TMC125 each patient was taking.

Overall, the patients taking TMC125 had comparable rates of side-effects to those taking placebo (92 vs. 91%). The commonest side-effects were diarrhoea (25 vs. 38%), headache (19 vs. 17%), rash (17 vs. 11%) and nausea (17 vs. 23%). None of these differences were statistically significant (p > 0.05).

The investigators found no significant differences in the rates of severe (grade 3 or 4) side-effects or laboratory abnormalities between the TMC125 and placebo groups, although the investigators were unable to conclude from the data available whether pancreatitis was associated with TMC125 or not due to the low number of cases they saw.

There were also no observable differences in the rate of side-effects between the three doses of TMC125 tested. However, the design of the study led to the patients receiving the highest dose of 1200mg twice a day being followed up for a median of 24 weeks, in contrast to 47 weeks for the 400mg group, 32 weeks for the 800mg group and 40 weeks for the placebo group. The shorter follow-up in the group receiving the highest dose may have led to an underestimation of the drug’s adverse effects at this dose.

The researchers wished to examine the incidence of rash and of nervous and psychiatric disorders in more detail, as these are major side-effects of the other available NNRTIs, nevirapine and efavirenz, respectively.

In contrast to nevirapine, TMC125 was not associated with an increased risk of rash across the three doses and in comparison to placebo, and the rate of rash was not different in men and women or in patients with different CD4 cell counts at the start of the study. The investigators concluded that only 8% of the patients had rash that was possibly related to TMC125, and these were generally mild or moderate in nature.

Similarly, the incidence of psychiatric disorders was similar in TMC125 and placebo groups (13 vs. 11%), as were the rates of nervous disorders such as headache, dizziness and insomnia.

“TMC125 was generally safe and well tolerated at doses up to 1200mg twice a day,” the researchers concluded. “No significant patterns of [liver toxicity] or neuropsychiatric disorders were detected.”

Efficacy and tolerability

The second study, TMC125-C223, set out to compare the antiviral efficacy of the 400 and 800mg twice-daily doses of TMC125 in patients with NNRTI resistance and three or more protease inhibitor resistance mutations.

The investigators randomised 199 patients to receive one of these doses in combination with a background regimen, or ‘active control’: the best available regimen from licensed antiretroviral agents. As in the first study, all of the patients were failing their current antiretroviral drug regimen, with a median viral load of 50,100 copies/ml and CD4 cell count of 99 cells/mm3.

After 24 weeks, the median reduction in viral load was 1.04 log10 for the 400mg group and 1.18 log10 for the 800mg group, under the assumption that the patients who did not complete the study experienced failure of the treatment regimen. In contrast, the patients taking the active control regimen had viral loads a median of 0.19 log10 below baseline. This was significantly less than in both TMC125 groups (p < 0.05).

These changes in viral load were mirrored by increases in CD4 cell count. While patients taking the active control regimens had a median increase of 10 cells/mm3, the patients taking TMC125-based regimens had increases of 47 and 48 cells/mm3.

“TMC125 is the first NNRTI to show significant activity in patients with prior NNRTI failure,” the investigators concluded. “TMC125 has the potential to be the first NNRTI to enable sequencable use of this drug class.”

The investigators also analysed the incidence of side-effects in this study. They repeated the findings of the earlier safety and tolerability study, finding no significant differences between TMC125 doses.

Comparisons between patients taking TMC125 and the active control could not be made due to many of the patients in the active control group stopping their assigned treatment early. After 24 weeks, 95% of the active control group had left the study, compared to 25% of those taking TMC125, with most of these being due to virological failure (75 vs. 6%).

Patients in the active control group who discontinued their assigned treatment went on to be offered TMC125 as part of a roll-over study.

Future directions

Based on the findings of these two studies, Tibotec selected the 800mg twice a day dose for future work. However, Julio Montaner and Jeffrey Nadler, presenting, revealed that the company has developed a new 200mg twice-daily formulation of TMC125. This tablet produces similar drug levels to the 800mg formulation used in these studies.

The new formulation is currently being studied in phase III trials of TMC125. Phase III trials are large, multicentre studies comparing a drug to a placebo or to the current standard of care. These trials usually form the final stage necessary before the drug’s developers can apply for its approval. Once the phase III trials of TMC125 are complete, they will indicate whether the drug will live up to its expectations by providing a new treatment option for patients who have experienced failure of NNRTI-based regimens.

References

Montaner J et al. Safety and tolerability of TMC125 in 3-class-experienced HIV-infected patients: 24-week primary analysis of trial TMC125-C203. Tenth European AIDS Conference / European AIDS Clinical Society, Dublin, abstract LBPS3/7B, 2005.

Nadler JP et al. Efficacy and tolerability of TMC125 in HIV patients with NNRTI and PI resistance at 24 weeks: TMC125-C223. Tenth European AIDS Conference / European AIDS Clinical Society, Dublin, abstract LBPS3/7A, 2005.

 
23 June 2005

Tipranavir (Aptivus) Approved by US Food and Drug Administration

 

On June 22, 2005, the US Food and Drug Administration (FDA) granted accelerated approval of APTIVUS (tipranavir), a protease inhibitor. APTIVUS, co-administered with 200 mg of ritonavir, is indicated for use as part of combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors.

FDA reviewed and approved APTIVUS within a six month time frame.


Clinical Study Results
The approval of APTIVUS/ritonavir is based on analyses of plasma HIV-1 RNA levels in two controlled phase III studies of APTIVUS/ritonavir of 24 weeks duration.  Both studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV­1 replication despite ongoing antiretroviral therapy. The results of the two phase III studies showed a statistically significant greater percentage of HIV-positive patients taking APTIVUS/ritonavir achieved treatment response versus the comparator group (40% vs. 18%). Treatment response was defined as a confirmed 1 log10 or greater decrease in HIV RNA from baseline.


Dosage and Administration
The approved dose of APTIVUS is 500 mg taken with 200 mg of ritonavir, twice daily with food. APTIVUS must be co-administered with 200 mg of ritonavir to exert its therapeutic effect. Failure to correctly co-administer APTIVUS with ritonavir will result in reduced plasma levels of tipranavir that will be insufficient to achieve the desired antiviral effect. Taking the drug with food improves absorption.


Usage Information:
The following points should be considered when initiating therapy with APTIVUS/ritonavir:

·       The use of other active agents with APTIVUS/ritonavir is associated with a greater likelihood of treatment response.

·       Genotypic or phenotypic resistance testing and/or treatment history should guide the use of APTIVUS/ritonavir.  The number of baseline primary protease inhibitor mutations affects the virologic response to APTIVUS/ritonavir.

·       Because APTIVUS can cause serious liver toxicity, liver function tests should be performed at initiation of therapy with APTIVUS/ritonavir and monitored frequently throughout the duration of treatment

·       Use caution when prescribing APTIVUS/ritonavir to patients with elevated transaminases,  Hepatitis B or C co-infection, or other underlying hepatic (liver) impairment

·       APTIVUS used with low-dose ritonavir has many drug interactions. Therefore, patients should report to their health care provider the use of any other prescription, non-prescription medication or herbal products, particularly St. John's Wort.  Certain medicines such as antiarrhythmics (medicines that treat irregular heart beats), antihistamines,  ergot derivatives (found in some medicines to treat migraine headaches), medicines that speed up the digestive tract, herbal products,  some medicines that lower cholesterol levels, and  medicines to treat mental problems should never be given with APTIVUS plus ritonavir because serious side effects could occur. 

Patients receiving estrogen-based birth control pills or patches should be instructed that additional or alternative forms of birth control should be used when taking APTIVUS. 

The extensive drug-drug interaction potential of APTIVUS/ritonavir when co-administered with multiple classes of drugs must be considered prior to and during APTIVUS/ritonavir use.

·       The risk-benefit of APTIVUS/ritonavir has not been established in treatment-naïve adult patients or pediatric patients.

·       There are no study results demonstrating the effect of APTIVUS/ritonavir on clinical progression of HIV-1.


Safety Information:
The most commonly (> 3%) reported adverse reactions were diarrhea, nausea, fatigue, headache and vomiting. The most commo nly reported laboratory abnormalities were elevated liver enzymes, cholesterol and triglycerides.

 

Hepatotoxicity
The APTIVUS label includes a Black Box warning regarding hepatoxicity. Specifically, APTIVUS co-administered with low dose ritonavir has been associated with reports of clinical hepatitis and hepatic decompensation, including some fatalities. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of hepatotoxicity.

All patients should be followed closely with clinical and laboratory monitoring, especially those with chronic hepatitis B or C co-infection, as these patients have an increased risk of hepatotoxicity.  Liver function tests should be performed prior to initiating therapy with APTIVUS/ritonavir, and frequently throughout the duration of treatment.

In addition, APTIVUS is contraindicated in patients with moderate and severe (Child-Pugh Class B and C, respectively) hepatic insufficiency .

Sulfa Allergy
APTIVUS should be used with caution in patients with a known sulfonamide allergy. Tipranavir contains a sulfonamide component. The potential for cross-sensitivity between drugs in the sulfonamide class and tipranavir is unknown.

Rash
Mild to moderate rashes including urticarial rash, maculopapular rash, and possible photosensitivity have been reported in subjects receiving APTIVUS/ritonavir.   In Phase 2 and 3 trials rash was observed in 14% of females and in 8-10% of males receiving APTIVUS/ritonavir.  Additionally, in one drug interaction trial in healthy female volunteers given a single dose of ethinyl estradiol (a hormonal contraceptive) followed by APTIVUS/ritonavir, 33% of subjects developed a rash.  Rash accompanied by joint pain or stiffness, throat tightness, or generalized pruritus (itching) has been reported in both men and women receiving APTIVUS/ritonavir.

Ongoing Clinical Trials
Boehringer Ingelheim agreed to continue to evaluate the safety and efficacy of APTIVUS in the following patient populations:

·       Pediatric patients
·       Treatment-naïve adults
·       HIV-positive women
·       Hepatitis co-infected patients

Additional drug-drug interaction studies are planned.

Currently there are seven other protease inhibitors approved by FDA for the treatment of HIV infection. These medications work at the final stages of viral replication and attempt to prevent HIV from making new copies of itself by interfering with the HIV protease enzyme. As a result, the new copies of HIV are not able to infect new cells

The manufacturer of APTIVUS is Boehringer Ingelheim Pharmaceuticals.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

 

See site information on tipranavir.
26 May 2005
Fortovase (soft-gel capsule form of saquinavir) To Be Discontinued February 15, 2006

 

Roche Pharmaceuticals, of Nutley, New Jersey, has issued a Dear Health Care Provider letter to inform the clinical community that commercial distribution of Fortovase, the 200-mg soft-gel formulation of saquinavir, will be discontinued by February 15, 2006.

The letter cites decreased demand for Fortovase as the reason for the product's discontinuation.

Invirase, another formulation of saquinavir manufactured by Roche Pharmaceuticals, will continue to be available in 200-mg and 500-mg formulations. 

Roche suggests that physicians refrain from starting Fortovase treatment in their HIV-positive Patients at this time, and encourages prescribing health care providers to discuss appropriate alternative treatment regimens with patients currently receiving Fortovase.

The complete Dear Health Care Provider letter is available at http://www.invirase.com/pdf/FTVDearDoctorFINAL.pdf
 

Source: FDA
20 May 2005

FDA Antiviral Drugs Advisory Committee Recommends Accelerated Approval for Experimental Protease Inhibitor Tipranavir (Aptivus)

 

Boehringer Ingelheim Pharmaceuticals, Inc. announced today that the US Food and Drug Administration’s (FDA) Antiviral Drugs Advisory Committee has recommended approval of the company’s experimental HIV protease inhibitor tipranavir (Aptivus). Although the FDA is not bound to accept the recommendations of its advisory committees, it almost always does.

 

Tipranavir is a non-peptidic protease inhibitor that requires “boosting” with low-dose ritonavir (Norvir) and must be used in combination with other antiretroviral agents.

 

Following are excerpts for the text of the company’s announcement about today’s recommendation of approval for tipranavir:

“We are pleased with the committee’s recommendation and commend its thorough discussion of the tipranavir clinical data,” said Burkhard Blank, M.D., Senior Vice President, Medical and Drug Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.  “We look forward to working with the FDA on the comments raised by the Advisory Committee and on the next steps of the application review process.”

 

The committee's positive recommendation is based on data from two large, well-controlled Phase 3 clinical trials, RESIST-1 and RESIST-2, conducted in protease inhibitor (PI)-resistant treatment-experienced patients.  These patients had taken three classes of anti-HIV drugs and were failing their PI-based regimen at the time of study entry.  These trials examine the treatment response of tipranavir boosted with ritonavir (TPV/r) versus a comparator group in which patients received one of several marketed ritonavir-boosted PIs.  In addition, patients in both arms received an optimized background regimen of other antiretroviral drugs.

 

Following the expected official approval of tipranavir, Boehringer Ingelheim will continue to provide the drug to eligible patients prior to its commercial availability through a Compassionate Use Program, which is being run as an Expanded Access Program in the U.S.
18 May 2005
On May 12, 2005, FDA approved new labeling for Viread (tenofovir disoproxil fumarate/TDF). The label was updated to include results from Study 903, specifically, the 144 week efficacy and safety data in treatment-naïve patients. Study 903 fulfills part of the requirement for traditional approval by confirming long-term efficacy in treatment-naïve patients and by providing long-term safety information with respect to bone effects.
 
The following changes were made to the package insert:
 
Description of Clinical Studies
 

The 144-week efficacy data from Study 903 was added. Sixty-eight percent of patients who received Viread in combination with Epivir (lamivudine) and Sustiva (efavirenz) achieved and maintained confirmed HIV RNA < 400 copies/mL at Week 144 compared to 62% of patients who received Zerit (stavudine) in combination with Epivir and Sustiva.
 
New text describing the genotypic analysis performed during Study 903 was added as follows:
 
"Genotypic analyses of patients with virologic failure showed development of efavirenz-associated and lamivudine-associated mutations to occur most frequently and with no difference between the treatment arms. The K65R mutation occurred in 8 patients on the Viread arm and in 2 patients on the stavudine arm. Of the 8 patients who developed K65R in the VIREAD arm through 144 weeks, 7 of these occurred in the first 48 weeks of treatment and one at week 96. Other mutations resulting in resistance to VIREAD were not identified in this study."
 
Precautions
 
The Bone Effects subsection was updated with Study 903 data through 144 weeks of dosing as follows:
 
In study 903 through 144 weeks, decreases from baseline in bone mineral density (BMD) were seen at the lumbar spine and hip in both arms of the study. At week 144, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in patients receiving VIREAD + lamivudine + efavirenz (-2.2% ±3.9) compared with patients receiving stavudine + lamivudine + efavirenz (-1.0% ±4.6).

Changes in BMD at the hip were similar between the two treatment groups (-2.8% ±3.5 in the VIREAD group vs. -2.4% ±4.5 in the stavudine group). In both groups, the majority of the reduction in BMD occurred in the first 24-48 weeks of the study and was sustained through Week 144. Twenty-eight percent of VIREAD-treated patients vs. 21% of the stavudine-treated patients lost at least 5% of BMD at the spine or 7% of BMD at the hip.

Clinically relevant fractures (excluding fingers and toes) were reported in 4 patients in the VIREAD group and 8 patients in the stavudine group. In addition, there were significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide and urinary N-telopeptide) in the VIREAD group relative to the stavudine group, suggesting increased bone turnover. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in the VIREAD group.

Except for bone specific alkaline phosphatase, these changes resulted in values that remained within the normal range. The effects of VIREAD-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown.
 
Bone monitoring should be considered for HIV infected patients who have a history of pathologic bone fracture or are at risk for osteopenia. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected then appropriate consultation should be obtained."
 
A new paragraph, "Immune Reconstitution Syndrome," was added. This paragraph will be incorporated into the labels of all antiretroviral drugs.
 
"Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including VIREAD. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis), which may necessitate further evaluation and treatment."
 
Adverse Reactions
 
Text and tables displaying Selected Treatment-Emergent Adverse Events (Grades 2-4) and Grade 3/4 Laboratory Abnormalities in Study 903 were updated with data through 144 weeks of dosing.
 
In the Post Marketing Experience section, increased amylase, increased liver enzymes, hepatitis, and nephrogenic diabetes insipidis were added to the list of reported disorders.
 
 Source
 US Food and Drug Administration
11 May 2005

Abbott Applies for FDA Approval of New Formulation of Lopinavir/Ritonavir (Kaletra)
 

Abbott announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for the approval of a new, more convenient tablet formulation of its protease inhibitor (PI) lopinavir/ritonavir (Kaletra).

 

The tablet was developed using a proprietary novel melt-extrusion technology intended to allow patients to take fewer tablets per dose as part of their treatment regimen. In addition, the tablet would not require refrigeration, as the current soft-gel capsule formulation does. Following is the text of the Abbott announcement:

 

“If approved, the new tablet will provide patients with a tablet composed of 200 mg lopinavir and 50 mg ritonavir, as compared to the current soft-gel capsule, which contains 133.3 mg lopinavir and 33.3 mg ritonavir. It also reduces the number of Kaletra pills patients need to take per day from six to four as part of their HIV treatment regimen. The tablet formulation would also eliminate the need for refrigeration of the medication.

 

"As an HIV treatment educator and a patient, I know that patients continue to have many unmet needs related to their treatment regimens," said Octavio Vallejo, faculty, The UCLA Pacific AIDS Education and Training Center. "We are pleased that Abbott is striving to enhance Kaletra, which has been an important part of HIV treatment regimens for the past several years."

 

“The submission package included data from bioequivalence studies. The company has plans to conduct clinical trials in patients living with HIV.”

 

Source
Abbott Laboratories. ABBOTT SUBMITS APPLICATION TO U.S. FDA FOR A NEW, MORE CONVENIENT FORMULATION OF KALETRA® (LOPINAVIR/RITONAVIR). Press Release. May 3, 2005.
29 April 2005
Kaletra (lopinavir/ritonavir co-formulation) Approved for Once-A-Day Dosing in Antiretroviral Naïve Patients

 

FDA today approved the use of KALETRA 800/200mg once-daily administration for the treatment of HIV-infection in therapy-naïve adult patients, based on review and analysis of two clinical trials comparing safety and efficacy of lopinavir (LPV)/ritonavir (RTV) 800/200 mg once daily (qd) and LPV/RTV 400/100 mg twice daily (bid), for a duration of at least 48 weeks in antiretroviral-naïve HIV-1 infected subjects.

At this time, once daily Kaletra is not approved for treatment experienced patients because trough concentrations of lopinavir are approximately 60% than that observed in the twice daily regimen and because there are no clinical studies comparing the two dosing schedules in treatment-experienced individuals. [from the FDA listserv]
7 April 2005
New DHHS Treatment Guidelines for Adolescents & Adults released
http://www.aidsinfo.nih.gov/guidelines/adult/AA_040705.pdf
or
http://www.aidsinfo.nih.gov/guidelines/default_db2.asp?id=50

 

6 March 2005
CROI 2005

 

Clinical Care Options has posted an excellent summary of the recent 12th Conference on Retroviruses and Opportunistic Infections February 22-25, 2005 in Boston.


 http://clinicaloptions.com/hiv/conf/croi2005/

 

18 February 2005
The 500 mg form of saquinavir hard gel capsule (Invirase) became available in the U.S. today.

 

23 December 2004
A 500 mg form of saquinavir hard gel capsule (Invirase) was approved by the FDA today.
6 December 2004
New Patient Information and Handouts on sister site HIVInfo.us:

 

A new handout was developed for "The Relationship With Your Healthcare Provider".   

Drug interactions were added to most of the protease inhibitor information sheets.

The staphylococcal infection info sheet was edited.
Extensive symptom management guidelines were published.

 

All are available in PDF format for printing and offline viewing.
3 December 2004
Generic didanosine delayed-release formulation approved by FDA.

 

The Food and Drug Administration (FDA) today (December 3, 2004) approved a generic formulation of Didanosine (ddI) Delayed Release capsules, 200 mg, 250 mg, and 400 mg for use in combination with other antiretroviral agents in the treatment of HIV-1 infection in adults. The product, manufactured by Barr Laboratories, Inc. of Pomona, NY will be available for use within the United States and foreign countries. It is the first approval in the United States of a generic antiretroviral product to treat HIV/AIDS.
2 December 2004
HIVManagement.org has added a new pain control and palliative care page which will be expanding as time goes on.

 

Palliative care and pain control are important topics in any area of medicine, but HIV/AIDS is associated with several uniquely painful situations.  Persons with HIV/AIDS are living longer and in some cases they are progressing into painful conditions.  The new pain control and palliative care page will hopefully provide simplified guidelines for management of these issues.

 

http://hivmanagement.org/palliative.html

 

13 November 2004
Glaxo and the FDA has announced the possible inferiority of the following specific combination of antiretrovirals:

 

efavirenz or nevirapine + tenofovir + didanosine-EC

 

or

 

Sustiva or Viramune + Viread + Videx-EC

 

The cause of the poor performance is unclear, but the problem does not appear to lie with the NtRTI/NRTI backbone. 

 

Until further notice this regimen should be avoided.  Patient's already on this regimen should probably be switched to alternative regimens as a variety of significant resistance mutations are associated with failure including K65R, M184V, K103N, etc.  Unfortunately I cannot find further info on this problem at this time.

 

30 October 2004
Newly revised Dept of Health and Human Services "Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents" released on October 30, 2004. 

 

Changes including demoting stavudine to an alternative NRTI and recommending tenofovir plus either lamivudine or emtricitabine as preferred therapy.

 

You can download the new guidelines here:
http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50

 

Or from this site at
http://hivmanagement.org/dhhsguideadultoct2004.pdf

 

Also there is an Adherence supplement:

http://hivmanagement.org/adherenceoct2004.pdf
10 October 2004
Thrombotic Complications in Patients Infected with HIV in the HAART Era [hivandhepatitis.com]

 

Researchers at the University of Washington School of Medicine in Seattle and Beth Israel Deaconess Medical Center in Boston identified 30 patients from an HIV outpatient clinic (treatment population, 650 persons) who had had a total of 43 venous or arterial thromboses during 1996-2002. Data pertaining to demographic characteristics, medical history, thrombosis presentation, and clinical outcomes were abstracted from patient medical records.

 

http://www.hivandhepatitis.com/recent/malignancies/100604_d.html
Tenofovir/FTC edges ahead of Combivir in head to head study at week 24 [aidsmap.com]

 

Gilead Sciences has revealed that a preliminary 24 week analysis of a study comparing tenofovir/FTC/efavirenz to AZT/3TC/efavirenz shows a significant advantage to the tenofovir/FTC arm, with a higher proportion of patients in this arm achieving and maintaining a viral load below 400 copies/ml at week 24...

 

http://www.aidsmap.com/en/news/60A006F7-996C-4290-81DB-D170281167A0.asp
Micafungin (parenteral) as effective as fluconazole for esophageal candidiasis [aidsmap.com]

 

A new antifungal drug called micafungin (Mycamine) is just as effective as fluconazole in the treatment of esophageal candidiasis in HV-positive people, according to findings from a randomized, double-blind study published in the September 15th edition of Clinical Infectious Diseases.

http://www.aidsmap.com/en/news/EBB1ACCD-DEE1-42B6-9D31-B040A8955BDE.asp
Viagra should carry HIV warning, say San Francisco health officials [aidsmap.com]

 

Anti-impotence drugs such as Viagra and Levitra should not be marketed without clear warnings about an increased risk of HIV and sexually transmitted infections, the San Francisco Department of Public Health said yesterday in a complaint to the US Food and Drug Administration

 

http://www.aidsmap.com/en/news/738382FC-7D93-4A90-9A34-4F61D315AFE7.asp

 

27 September 2004
An announcement letter was written to HIV care providers that the 150 mg gel caps of amprenavir (Agenerase) would be discontinued from manufacturing by the end of 2004.  The 50 mg caps and the solution will continue to be made.  The likely cause of this change is the availability of the superior prodrug, fosamprenavir.

 

7 September 2004
Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America were published in Clinical Infectious Diseases and on the WWW

 

http://www.journals.uchicago.edu/CID/journal/issues/v39n5/34135/34135.html or PDF HERE.

 

29 August 2004
Tenofovir/FTC edges ahead of ZDV/3TC in comparison trial [aidsmap.com]
 

Gilead Sciences has revealed that a preliminary 24 week analysis of a study comparing tenofovir/FTC/efavirenz to AZT/3TC/efavirenz shows a significant advantage to the tenofovir/FTC arm, with a higher proportion of patients in this arm achieving and maintaining a viral load below 400 copies/ml at week 24....

 

http://www.aidsmap.com/en/news/60A006F7-996C-4290-81DB-D170281167A0.asp
Pegylated interferon can cause serious eye problems in HIV/HCV coinfected patients [aidsmap.com]

 

Treatment with pegylated interferon alpha-2b (PegIntron) and ribavirin can cause serious eye problems in individuals coinfected with HIV and hepatitis C virus according to an article published in the September 3rd edition of AIDS.The US investigators recommend that patients coinfected with HIV and hepatitis C and treated with pegylated interferon and ribavirin receive regular ophthalmic monitoring...
 

http://www.aidsmap.com/en/news/52F9ED92-DEF3-47EE-AB4D-1E298ADABA88.asp
Hepatitis C and HIV: genotype 1 is not a lost cause, report Spanish doctors [aidsmap.com]

 

Spanish researchers have reported the best ever response to pegylated interferon and ribavirin in people coinfected with HIV and hepatitis C genotype 1 (the most difficult to treat variant). In a randomized study given fast track publication in the September 3rd edition of AIDS, the Barcelona group report that almost half the genotype 1 patients who received pegylated interferon showed a sustained response to treatment.
 

http://www.aidsmap.com/en/news/48DAD871-F308-40C5-B0EE-326672AB1830.asp
Risk Factors for Hepatic Decompensation in Patients with HIV-HCV Coinfection and Liver Cirrhosis During Interferon-based Therapy   

 

Hepatic decompensation was reported from two recent trials (APRICOT and RIBAVIC ) assessing interferon (IFN)-based treatment of hepatitis C virus (HCV) in HIV-HCV-coinfected patients. The current study, published in AIDS (September 3, 2004), identifies risk factors associated with hepatic decompensation in APRICOT.

 

http://www.hivandhepatitis.com/hiv_hcv_co_inf/082704_a.html

Lung Cancer in Patients with HIV Infection [hivandhepatitis.com]

 

The improved survival of patients since the use of HAART has led to the reporting of non-AIDS defining tumors, such as lung cancer (LC).

This study consisted of an analysis of the records of 22 HIV-infected patients with LC diagnosed in three hospitals located in the Paris area (France).

 

http://www.hivandhepatitis.com/recent/ois/lung/082704_c.html
Stavudine-Related Hyperlactemia Resolves after NRTI Switch [hivandhepatitis.com]

 

Stavudine-related hyperlactatemia does not recur after changing to another nucleoside reverse transcriptase inhibitor (NRTI), according to a report in the August 1st issue of the Journal of Acquired Immune Deficiency Syndromes.  "Patients who have symptomatic hyperlactatemia do not have to abandon the NRTI class," Dr. J. Tyler Lonergan from University of California at San Diego Medical Center, San Diego, California told Reuters Health. "Instead, they can safely switch to other NRTIs with less potential to induce mitochondrial toxicity."

 

http://www.hivandhepatitis.com/recent/switch/082704_e.html
New on HIVinfo.us: Dapsone info and rifabutin info page and PDFs posted. 

 

 

22 August 2004
L-acetyl-carnitine effective for AIDS drug-related neuropathy! [hivandhepatitis.com]
 

Acetyl-L-carnitine is a safe, well-tolerated agent that reverses nerve damage caused by nucleoside reverse transcriptase inhibitors (NRTI) treatment of HIV, British investigators report.  Acetyl-L-carnitine (ALCAR) relieves pain in patients with distal symmetrical polyneuropathy due to antiretroviral therapy, Dr. Mike Youle and his associates note in their report, published in the July 23rd issue of AIDS. However, it was unclear if the agent has an effect on neuronal regeneration...


http://www.hivandhepatitis.com/hiv_and_aids/neuropathy/081104_a.html

 

Two possible sources of L-acetyl carnitine are the following: (the purity may not be necessarily up to FDA standards)
 Jarrow's Acetyl L-Carnitine 500 mg #60 19.95
Drugstore.com/GNC Acetyl L-Carnitine  500 mg #30 29.99
Scientists discover new approaches to purging HIV reservoir [aidsmap]

 

Researchers at the National Cancer Institute (NCI), part of the United States National Institutes of Health, have discovered new information about how HIV could evade eradication from the body. In a study published in the August 16th, 2004 Journal of Virology, NCI HIV and AIDS Malignancy Branch scientists identified several possible gene targets and two drugs to flush out long-lasting HIV reservoirs that current treatments do not affect. They also established a connection between HIV and several other genes not previously associated with the virus and found new possible targets for blocking HIV replication...

 

http://www.aidsmap.com/en/news/6B6DC32A-B85E-4461-8592-6075406EA72C.asp
HAART alone is not enough for treatment of moderate-severe KS [aidsmap]

 

Individuals with moderate or advanced Kaposi’s sarcoma (KS) have much higher rates of partial or complete remission of lesions when highly active antiretroviral therapy (HAART) is combined with the liposomal chemotherapeutic agent, pegylated liposomal doxorubicin (PLD; Caelyx) than with HAART alone, according to a letter by Spanish researchers in the most recent issue of the journal AIDS. This is the first randomised study to assess the direct effect of HAART on HIV-related KS regression, and suggests that, unlike previous studies, HAART alone is not sufficient when KS is moderate or severe...
 

http://www.aidsmap.com/en/news/CC924910-E238-4CEE-885F-0F250D34063A.asp
Overview of antiretroviral clinical trials from Bangkok International AIDS Meeting  [hivandhepatitis.com]

 

http://www.hivandhepatitis.com/2004icr/aids2004/dos/0730/080604_a.html
New on HIVinfo.us: Clarithromycin, azithromycin, fluconazole, and rifabutin info pages and PDF posted.  Truvada and Epzicom were also added.

 

3 August 2004
Two NEW FDA drug approvals!

 

Epzicom: abacavir 600 mg + lamivudine 300 mg co-formulated, administered once a day for persons in whom full-dose abacavir and lamivudine are appropriate

Truvada: tenofovir 300 mg + emtricitabine 200 mg co-formulated, administered once a day for persons in whom full-dose tenofovir and emtricitabine are appropriate

 

Both drugs have been added to the fixed dose combination NRTI section of the NRTI info page on this site or click Epzicom or Truvada.
New on HIVinfo.us: Sulfamethoxazole/trimethoprim information sheet and PDF posted.  Truvada and Epzicom will be added later today.

 

 

25 July 2004
New on this site:  The antiretroviral tables were updated and links were added from the tables for adjusting NRTIs in the setting of nephropathy.
New on HIVinfo.us: Adherence pages/handouts, HIV transmission information pages, and prevention for positives information/handouts were added.
Medscape continues their history of excellent conference coverage with extensive summaries of the XV International AIDS Conference in Bangkok July 11-16.  CME is available.

 

http://www.medscape.com/viewprogram/3248

 

6 July 2004
New on this site:  Adherence information was expanded dramatically.  Also investigational drugs were updated.
The http://www.hiv-druginteractions.org/ has published summaries of key pharmacokinetic data on double boosted protease inhibitors.  This is an important read.  Triple or quadruple drug interactions cannot be accurately predicted in some cases.

 

http://www.hiv-druginteractions.org/frames.htm?new/Content.asp?ID=168
Sister site HIVInfo.us now has PDF drug handouts for each of the antiretroviral medications that are available as well as handouts on HIV 101, staph infections, lab test interpretation, vaccinations, and prevention for positives.  The handouts can be downloaded by the patient or provider from

 

http://hivinfo.us/pdf.html

 

 

27 June 2004
New on this site:  NRTI renal and hepatic dosing information is now found on the NRTI Info page, and there is a new look for the whole site in terms of colors and some formatting.  Also loads of information corrections and new information on almost every page.  Also this HIV information updates page was launched.
Infection with drug-resistant HIV has little effect on CD4 cell counts in the absence of therapy [aidsmap.com]
 

Infection with a drug-resistant strain of HIV slightly accelerates CD4 T-cell decreases in the first year after seroconversion, but causes no difference in CD4 cell counts thereafter, according to a research letter published in the July 2nd edition of AIDS.


http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2765
Evaluation of a new TB test highlights ongoing dilemmas of TB/HIV management [aidsmap.com]

 

A new prototype test for TB lacks sufficient sensitivity as a sole test for TB in a predominately HIV-infected population in Botswana, according to a study published in July 1st edition of Clinical Infectious Diseases. Five other commercially available serodiagnostic TB tests evaluated in this study were also found to be insufficiently sensitive as sole diagnostics.

 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2762
Risk of severe liver toxicities if nevirapine used in HAART in pregnant women with CD4 above 250 [aidsmap.com]

 

Anti-HIV therapy based on the non-nucleoside (NNRTI) nevirapine (Viramune) is associated with an increased incidence of serious liver toxicities in HIV-positive pregnant women with a CD4 cell count above 250 cells/mm3, according to a study published in the July 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The study was designed to compared the safety and efficacy of HAART regimens based on either the NNRTI nevirapine or the protease inhibitor nelfinavir (Viracept) in HIV-positive pregnant women, however the study was stopped early because of a higher than expected incidence of serious side-effects in the nevirapine arm.

 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2762
Harmless virus slows HIV progression by stimulating chemokine release [aidsmap.com]

 

A harmless hepatitis virus slows the progression of HIV by stimulating the release of chemokines, according to a study presented in the June 19th edition of The Lancet. The authors suggest that the hepatitis G virus, also known as GBV-C, could be developed as a treatment to slow the progression to AIDS.

 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2758
Over a quarter of HIV-positive children on treatment have lipodystrophy in European study [aidsmap.com]

 

Over a quarter of HIV-positive children and adolescents had body fat redistribution and over a third had elevated blood lipids according to a European study published in the July 2nd edition of AIDS. An AIDS diagnosis, female sex, and the use of a protease inhibitor or d4T were all independently associated with body fat redistribution and abnormal blood fats in the children and adolescents.

 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2760
Black Americans respond less well to interferon treatment for HCV [aidsmap.com]

 

In the United States the rate of HCV infection among blacks is estimated at 2-3 times higher than the rate seen in whites, and blacks appear less likely to naturally clear the virus. Several retrospective studies with small numbers of black participants have shown that blacks do not respond as well as whites to interferon-based therapy. Two new prospective studies confirm this finding.

 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2757
New technique enables diagnosis of HIV within a week of infection, measures viral load to 2 copies [aidsmap.com]

 

A new diagnostic technique has been developed which allows for the diagnosis of HIV within less than one week of infection. The new tool makes possible the detection of HIV viral load as low as two copies/ml, considerably lower than the limit of detection available with the RNA PCR tests currently used to measure viral load. The development of these improved testing methods is reported in the July edition of the American Journal of Clinical Pathology, which is now available on-line.

 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2756
Rectal secretions from men who have sex with men contain more HIV than blood or semen [aidsmap.com]

 

Levels of HIV RNA in rectal mucosa secretions from men who have sex with men (MSM) are higher than those in blood and semen, according to a study presented in the July 1st edition of The Journal of Infectious Diseases. The results suggest that unprotected insertive anal intercourse may involve exposure to higher levels of free virus than previously believed, even where the receptive partner's plasma viral load is undetectable on HAART.

 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2753

 

 

17 June 2004

Tipranavir may reduce levels of other protease inhibitors [aidsmap.com]
 

After the addition of tipranavir in BI 1182.51 at week 2 levels of the (other) protease inhibitors fell sharply. When PK parameters for each of the protease inhibitors after the addition of tipranavir are expressed as a ratio of the pre-tipranavir levels the extent of the effect is clear:

  • Amprenavir: AUC and Cmin 0.5, Cmax 0.6
  • Lopinavir: AUC 0.5, Cmax 0.6, Cmin 0.4
  • Saquinavir: AUC 0.3, Cmax 0.3, Cmin 0.2

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2751
Hepatitis B can flare up even during lamivudine treatment in HIV-positives [aidsmap.com]

 

Use of antiretroviral therapy can lead to immune reconstitution hepatitis in HIV/HBV-coinfected patients even if they are taking lamivudine, according to a pair of case reports in the July 1st edition of Clinical Infectious Diseases.
 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2750
HAART is effective in prisoners, but benefit may be lost upon release [aidsmap.com]

 

Inmates respond well to anti-HIV therapy during incarceration, but this benefit is often lost after release, according to an American study published in the June 15th edition of Clinical Infectious Diseases. The results suggest the need for effective community-based programs to assist former prisoners after they are released.


http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2749
Double-boosted saquinavir/atazanavir study lays ground for PI-only regimen [aidsmap.com]

 

A 32-day study of the pharmacokinetics (PK) of the protease inhibitors (PIs) hard-gel saquinavir (Invirase) and atazanavir (Reyataz), boosted by 100mg of ritonavir (Norvir) has found that the plasma concentrations of saquinavir and ritonavir were significantly enhanced, and that atazanavir further enhanced the boosting effect of ritonavir on saquinavir.


http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2745
Study finds that 8% of newly diagnosed HIV patients in US have drug resistance [aidsmap.com]

 

Resistance testing of individuals recently diagnosed with HIV before the initiation of HAART would identify a substantial number of patients with mutations causing resistance to HIV drugs, according to a US study published in the June 15th edition of The Journal of Infectious Diseases. The investigators also established that gay men, whites and patients whose partners were taking HAART, were the groups of recently diagnosed patients most likely to have drug-resistant mutations prior to initiating treatment with anti-HIV drugs.
 

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2754

 

 

16 June 2004
Atazanavir significantly reduces lipids 12 weeks after switching from nelfinavir [aidsmap.com]

 

Switching from nelfinavir-based HAART to atazanavir (Reyataz) returns lipids to pre-treatment levels after three months and maintains viral suppression for at least 36 weeks after the switch, according to the results of a Bristol-Myers Squibb-sponsored study published in the June 1st issue of the Journal of Acquired Immune Deficiency Syndromes.

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2730
Delaying HAART until CD4 counts are below 200 cells/mm3 results in poorer outcome [aidsmap.com]

 

HIV-positive patients beginning antiretroviral therapy after their CD4 counts have fallen to below 200 cells/mm3 are less likely to exhibit full immune reconstitution than those who start with more CD4 T-cells, according to findings presented in the June 1st edition of the Journal of Acquired Immune Deficiency Syndromes. However, the study confirms that suppression of viral load is the best indicator of successful therapy.

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2728
HCV coinfection does not hasten HIV disease progression finds pre-HAART study [aidsmap.com]

 

Coinfection with hepatitis C virus does not hasten HIV disease progression, according to a retrospective analysis of data gathered in the pre-HAART era and published in the May edition of HIV Medicine. Investigators from the CAESAR study also found that injecting drug use and abnormal liver function were the strongest predictors of HCV coinfection, and that few gay men appeared to have been infected with HCV through sex.

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2727
The http://www.hiv-druginteractions.org/ website announces release of the PDA versions of its HIV drug interaction charts.  They are available in Palm and Pocket PC formats free of charge with registration.