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Research Focus: Recent Developments in HIV Therapeutics


Research Focus: Recent Developments in HIV Therapeutics

Dr Boyle is associate professor, department of international medicine and infectious diseases (Courtesy), New York Presbyterian Hospital–Weill Medical College of Cornell University, New York. Dr Elion is associate professor of clinical medicine, George Washington University Medical Center, Washington, DC. Dr Cohen is research director, Community Research Initiative of New England, Springfield, Mass, and clinical instructor, Harvard Medical School, Boston. Dr Moyle is associate director of HIV research and associate specialist in HIV/GU medicine at Chelsea & Westminster Hospital, London.

New developments continue to unfold in HIV therapeutics. This column will review some of the more important recent developments, ie, those that are likely to influence prescribers regarding antiretroviral choices and could potentially influence guideline recommendations in 2007.

The current International AIDS Society(IAS)-USA panel treatment recommendations for adults with HIV infection and the Department of Health and Human Services (DHHS) guidelines for the use of antiretroviral agents in HVI-1-infected adults and adolescents both recommend efavirenz as the initial NNRTI in antiretroviral-naive patients, except in the first trimester of pregnancy or in sexually active women with child-bearing potential who are not using effective contraception.1,2 In fact, the strength of the data surrounding efavirenz has grown so that for most clinicians the decision is not which NNRTI to use but whether to start therapy with efavirenz or a ritonavir-boosted protease inhibitor (PI).

Until recently, the decision to start antiretroviral therapy with an NNRTI was affected to some extent by the limited data comparing an NNRTI with a ritonavir-boosted PI and establishing NNRTI efficacy in patients with low CD4 counts or high HIV RNA levels. Over the past year, however, studies have demonstrated that efavirenz is more effective than lopinavir/ritonavir (lopinavir/r) in antiretroviral-naive patients and is equipotent across all CD4-count and HIV RNA-level spectra.

A large AIDS Clinical Trials Group (ACTG) study, ACTG 5142, compared, inter alia, efavirenz plus 2 NRTIs with lopinavir/r plus 2 NRTIs in antiretroviral-naive patients and found that in many respects lopinavir/r was inferior to efavirenz. Compared with the efavirenz arm, the lopinavir/r arm had a significantly shorter time to virological failure, had significantly fewer patients achieve an HIV RNA level below 50 copies/mL at 96 weeks, and tended to have a shorter time to regimen completion (combination of virological failure or toxicity-related discontinuation). While the efavirenz arm did not achieve quite as robust a CD4 count increase as the lopinavir/r arm, it is unlikely that these small differences are clinically relevant.3 The expected differences in resistance in patients with incomplete suppression were observed in an interim analysis, and it remains an ongoing debate whether the differences are sufficient to alter the overall conclusion about superior response rates with efavirenz.

The recently presented TEQUILA and SUSKA studies support the findings of ACTG 5142. In the TEQUILA study, 1160 patients who started either of these 2 regimens (efavirenz, 665; lopinavir/r, 495) with a variety of NRTI backbones were retrospectively evaluated.4 At baseline, the patients had very advanced HIV disease, with a median CD4+ cell count of 35 to 37/µL and an HIV RNA level of 5.26 to 5.30 log10 copies/mL. After more than 3 years of therapy, the virological and immunological outcomes were relatively similar in the 2 arms, except for a significant difference in time to treatment discontinuation for any cause, which significantly favored efavirenz.

The SUSKA study retrospectively evaluated 1532 patients with less advanced disease but still with a median CD4+ cell count of less than 200/µL and a median HIV RNA level greater than 5 log10 copies/mL.5 It found that the lopinavir/r arm had significantly shorter times to virological failure than the efavirenz arm (884 vs 1407 days; P =.007); this finding persisted even in patients with a baseline HIV RNA level greater than 5 log10 copies/mL, a baseline CD4+ cell count of less than 100/µL, history of an AIDS event, or coinfection with hepatitis C virus. Thus, these studies in the real world of clinic-based cohorts appear to reinforce and expand the findings of ACTG 5142, which established that in antiretroviral-naive patients, efavirenz is at least as good as, if not better than, lopinavir/r.

Moreover, a subanalysis of ACTG 5095 has provided data that definitively demonstrate that efavirenz is effective across the spectrum of HIV RNA levels and CD4 counts.6 The efficacy of 2 efavirenz arms at 3 years was assessed across different levels of HIV RNA (less than 30,000 to 300,000 or more copies/mL) and CD4+ cell counts (500 or more to less than 50/µL) in the 765 patients randomized to those arms, and efavirenz was found to be equally effective across all HIV RNA levels and CD4 count strata.

In sum, studies to date indicate that efavirenz is superior to lopinavir/r--the ritonavir-boosted PI considered the gold standard of efficacy with regard to PI therapy--in antiretroviral-naive patients and that there is no CD4 count or HIV RNA level that appears to limit the effectiveness of efavirenz. These data would certainly seem to favor efavirenz-based therapy as the preferred initial antiretroviral treatment for most patients. This is especially so when the other benefits of efavirenz are considered, which include good tolerability, low toxicity, and the ultimate in simplicity: an entire regimen--efavirenz plus tenofovir plus emtricitabine--in a single tablet, once daily.

Both the current IAS-USA recommendations and DHHS guidelines now list multiple ritonavir-boosted PIs as "recommended" or "preferred" for antiretroviral-naive patients.1,2 Two recently reported studies, discussed at length in a previous column,7 led to changes in the guidelines and will be mentioned here only briefly.

The KLEAN study, which compared fosamprenavir/ritonavir (fosamprenavir/r) with lopinavir/r in 878 antiretroviral-naive patients, led to fosamprenavir/r being added as a recommended PI in the IAS-USA recommendations and a preferred PI in the DHHS guidelines.8 Referring to the KLEAN study, the DHHS committee stated, "In this study of treatment-naive subjects, twice-daily ritonavir-boosted fosamprenavir was noninferior to twice-daily lopinavir/ritonavir, and this supports the recommendation of twice-daily ritonavir-boosted fosamprenavir as a preferred PI component."2

While atazanavir/ritonavir (atazanavir/r) has been a recommended PI in the IAS-USA recommendations since 2004, because of a lack of comparative data, until recently it was not even an alternative PI in the DHHS guidelines. Study AI424-089 comparing atazanavir/r with unboosted atazanavir in 200 antiretroviral-naive patients changed that.9 AI424-089 was specifically cited by the DHHS committee when it added atazanavir/r to its preferred list, stating that the "comparative virologic efficacy to unboosted atazanavir in treatment-naive patients, the improved pharmacokinetics with ritonavir-boosting, and the experience of atazanavir plus ritonavir in treatment-experienced patients [citation omitted] supports its designation as a preferred regimen."2

While there has been significant evolution of the guidelines, especially the DHHS guidelines, in the past year, further changes may still need to be made. Recently reported studies, if confirmed, may eventually lead to the addition of saquinavir/ritonavir (saquinavir/ r) to the DHHS guidelines as a preferred, or at least an alternative, agent and the addition of fosamprenavir/r (1400/100 mg) as preferred or alternative once-daily therapy.

One notable difference between the IAS-USA recommendations and the DHHS guidelines is that while saquinavir/r is a recommended PI in the IAS-USA recommendations, it is not even listed as an alternative agent in the DHHS guidelines. In fact, in the DHHS guidelines, saquinavir/r is listed under "Other PI Options--Inferior to Preferred or Alternative PI Components."

Data presented at the 8th International Congress on Drug Therapy in HIV Infection, if confirmed in the entire cohort at 48 weeks, should change that. The GEMINI study is a prospective, randomized, multicenter, open-label study comparing saquinavir/r 1000/100 mg twice daily with lopinavir/r 400/100 mg twice daily in 337 antiretroviral-naive patients.10 In this study, the 500-mg film-coated tablet of saquinavir (3 pills twice a day including ritonavir) and the soft-gel capsule formulation of lopinavir/r (3 pills twice a day) were used, and both boosted PIs were given with an NRTI backbone of coformulated tenofovir/emtricitabine once daily.

The primary end point of the GEMINI study is the percentage of patients with an HIV RNA level below 50 copies/mL at 48 weeks; however, data from a planned interim analysis of the first 150 patients completing 24 weeks of treatment were presented at the 8th International Congress on Drug Therapy in HIV Infection. At baseline, those patients had mean HIV RNA levels of 5.1 and 5.2 log10 copies/mL (43% and 57% greater than 100,000 copies/mL) and CD4+ cell counts of 121 and 134/µL (47% and 56% less than 100/µL), respectively. At week 24, the virological and immunological responses were similar in the 2 groups, using either an intent-to-treat (Table 1) or an as-treated analysis.

Seven patients were considered to have experienced virological failure (5 with saquinavir/r; 2 with lopinavir/r), with adherence issues appearing to be the most common causative factor. At virological failure, the only new mutation found was M184V (n = 2); all of the other patients had either only the mutations present at baseline
(n = 3) or wild-type HIV (n = 2). Notably, there were no new primary PI mutations seen in either group, consistent with other studies with virological failures in the setting of boosted PIs, and there were no K65R mutations.

The 2 regimens had similar tolerability, except for an increased number of grade 2 to grade 4 GI events in the lopinavir/r arm (14 in saquinavir/r vs 23 in lopinavir/r). The 2 arms were similar with regard to mean changes in lipid values, another common issue with boosted-PI regimens, except that the lopinavir/r arm had a significantly greater mean increase in triglyceride levels (+88 vs +29 mg/dL; P =.020). In addition, it should be noted that the saquinavir/r arm had fewer patients with a cholesterol level of 200 mg/dL or greater (21% in saquinavir/r vs 38% in lopinavir/r; P = .036) or a triglyceride level of 400 mg/dL or greater (1% vs 13%; P =.009).

These preliminary data indicate that saquinavir/r is comparable to lopinavir/r regarding efficacy and better in some respects regarding tolerability and lipid levels. These data, if confirmed, may validate the decision of the IAS-USA committee to include saquinavir/r in its recommended agents and cause the DHHS committee to revisit this issue, much as this committee did recently with data supporting the addition of atazanavir/r and fosamprenavir/r to those guidelines.

While the IAS-USA recommendations do not specifically define the preferred dosing frequency, the DHHS guidelines list atazanavir/r as the only preferred once-daily PI, with lopinavir/r and fosamprenavir/r preferred as twice daily and an alternative for once daily either because of potency (fosamprenavir/r) or tolerability (lopinavir/r) concerns. Two recently reported trials indicate that fosamprenavir/r (1400/100 mg) may merit some attention, especially if larger comparative trials bear out what these relatively small trials have demonstrated.11,12 Because the trials have similar findings, only 1, ALERT, will be discussed here.

ALERT is a relatively small (N = 106), open-label, prospective study, sponsored by GlaxoSmithKline, comparing fosamprenavir 1400 mg plus ritonavir 100 mg once daily versus atazanavir 300 mg plus ritonavir 100 mg once daily, both given with fixed-dose tenofovir/emtricitabine. Thus, the dosing strategy being tested with fosamprenavir includes 100 mg less of ritonavir than the current FDA-approved dosing strategy. This dose was tested because earlier pharmacokinetic data suggested that decreasing the ritonavir dose to 100 mg did not lead to clinically significant changes in fosamprenavir levels but may improve tolerability and lessen the impact of the regimen on lipid levels.

The study enrolled 53 participants in each arm, with a median baseline HIV RNA level of 4.88 log10 copies/mL and a median baseline CD4+ cell count of 172/µL. The results at week 24, by an intent-to-treat, missing/discontinuation-equals-failure analysis and an on-treatment analysis are shown in Table 2.

Both regimens were well tolerated overall. At week 24, the changes in cholesterol levels were relatively similar in the 2 arms, but triglyceride level increases were higher in the fosamprenavir/r arm (44 vs 6 mg/dL). Hyperbilirubinemia associated with atazanavir was the most common laboratory adverse event.

Notably, despite this population having relatively poor renal function at baseline (61% with a baseline glomerular filtration rate [GFR] of between 50 and 90 mL/min by modification of diet in renal disease [MDRD]) and the use of relatively strict criteria for study discontinuation as a result of renal clearance decreases (either an estimated GFR change of more than 25% below baseline or a confirmed estimated GFR less than 50 mL/min), only 2 of the 106 patients had their regimen discontinued as a result of renal issues. While based on only 24 weeks, these preliminary data are in line with previous data demonstrating the safety of tenofovir with ritonavir-boosted PIs and suggest that this may be true even in patients with a somewhat decreased creatinine clearance at baseline.

This small trial indicates that fosamprenavir/r 1400/100 mg once daily may have potency similar to that of atazanavir/r 300/100 mg once daily. However, there was a difference reported in the implications of not achieving full suppression: new PI mutations developed in 2 patients in the fosamprenavir arm, while 1 patient with rebound in the atazanavir arm had no PI mutations. Although the numbers are small, these data do raise a concern about the potential impact of decreasing the effect of boosting when lowering the ritonavir dose. There still may be a difference in lipid level effects between these 2 regimens, with the edge going to atazanavir, but these differences appear to have been reduced.

Finally, data from a recent study demonstrate that tipranavir/ritonavir (tipranavir/r) should not be used in antiretroviral-naive patients.13 In this study, 2 tipranavir/r dosing arms (500 mg/200 mg twice daily and 500 mg/100 mg twice daily) were compared with lopinavir/r (400/100 mg twice daily), all given with a backbone of tenofovir and lamivudine. This 3-arm trial enrolled 558 patients, with a baseline median CD4+ cell count of 207/µL and a median HIV RNA level of 5 log10 copies/mL. About 16% of the enrolled patients were coinfected with hepatitis B or hepatitis C virus.

At week 48, there was a similar suppression rate to below 50 copies/mL noted in all arms: tipranavir/r 100, 65.8%; tipranavir/r 200, 66.7%; lopinavir/r, 69.2%. The protocol defined suppression as a confirmed HIV RNA level of less than 50 copies/mL, so the results were extended to include the week-60 results (because some achieved less than 50 copies/mL only by week 48). Based on these additional data, the lower limit of the 97.5% confidence interval for the difference between tipranavir/r 100 and lopinavir/r was 15.03, just below the prespecified cutoff of a 15% difference defined as noninferior. The trial ended with the conclusion that the tipranavir/r 100 arm could not be considered noninferior to the standard-of-care arm (lopinavir/r), and additional follow-up ended.

It is important to note, however, that the arm with tipranavir/r 200 (the dose used in treatment-experienced patients) was stopped because of a higher rate of grade 3/4 alanine aminotransferase elevations (17.7%) than that in the tipranavir/r 100 arm (5.9%) or the lopinavir/r arm (3.4%). There was no report of clinical hepatitis or hepatic failure, but the higher rate of alanine aminotransferase elevations was statistically significantly worse for the higher dose.

The authors concluded from these data that there is no recommended role for tipranavir/r at either tested dose in antiretroviral-naive patients who are infected with wild-type HIV. Thus, this trial, which attempted to extend the use of tipranavir to antiretroviral-naive patients, demonstrated instead that tipranavir, because of lack of efficacy or increased toxicity, should not be used in that patient population.

The IAS-USA and DHHS guidelines now list only fixed-dose, coformulated NRTIs as initial therapies of choice. The IAS-USA guidelines "recommend" zidovudine/ lamivudine, abacavir/lamivudine, or tenofovir/emtricitabine as the initial NRTI backbone, while the "preferred" NRTI combinations under the DHHS guidelines are zidovudine/lamivudine or tenofovir/emtricitabine, with abacavir/lamivudine listed as an alternative because of "the potential for serious abacavir-associated hypersensitivity reactions in 5% to 8% of patients."1,2

Recently reported studies have made it clear that there are many differences between the NRTI backbones recommended or preferred under these guidelines. In one report, Pozniak and colleagues14 described the 2-year follow-up data in GS 934, a comparison of efavirenz plus coformulated zidovudine/lamivudine and efavirenz plus tenofovir plus emtricitabine. The week-96 virological and immunological outcomes are shown in Table 3 and demonstrate overall superiority of the tenofovir plus emtricitabine arm over the zidovudine/lamivudine arm.

In addition to the differences noted above, significant differences also occurred with regard to:

• The number of patients with virological failure eligible for resistance testing (29 in the zidovudine/lamivudine arm vs 14 in the tenofovir/emtricitabine arm; P =.017).
• Rates of M184V at virological failure, with higher rates in the zidovudine/lamivudine arm (9 vs 2; P =.036).
• Rates of adverse events (11% vs 5%; P =.023) and, in particular, anemia (6% vs 0%; P < .001), both of which were higher in the zidovudine/lamivudine arm.
• GFR as measured by MDRD (108 vs 100: P =.006) but not Cockcroft-Gault (118 vs 119; P =.51), with no patients in the tenofovir/emtricitabine arm and 2 patients in the zidovudine/lamivudine arm experiencing a grade 1 or grade 2 change in serum creatinine level.

One of the most critical differences of the trial was the continued divergence of the amount of limb fat seen with dual energy x-ray absorptiometry scans at 48 and 96 weeks, with patients receiving tenofovir plus emtricitabine maintaining relatively normal subcutaneous fat levels, while the patients receiving zidovudine/lamivudine had significant losses (Figure).

The results of this trial reaffirm and expand the data previously presented from GS 903 in which tenofovir-treated patients maintained normal subcutaneous fat levels for 3 years, while those receiving stavudine had significant losses. Based on these 2 trials, it is reasonable to conclude that tenofovir is less likely to cause lipoatrophy than either of the thymidine analogues, stavudine or zidovudine.

These data indicate that in every important clinical end point, tenofovir plus emtricitabine is superior to zidovudine/lamivudine. In addition, tenofovir plus emtricitabine is now combined with efavirenz as a once-daily, single-tablet regimen, which may have benefits for adherence over twice-daily zidovudine/lamivudine. If these data are reaffirmed by long-term follow-up and other trials, there may be some impetus for the guideline committees to demote zidovudine/lamivudine to an alternative therapy to be used only in patients intolerant of or not suitable for treatment with preferred agents, such as tenofovir/emtricitabine or, as discussed below, perhaps abacavir/lamivudine.

Finally, as noted above, the DHHS committee lists abacavir/lamivudine as an alternative therapy because of concerns about the abacavir hypersensitivity reaction (HSR). Further studies may establish HLA-B*5701 screening as a clinical tool for avoiding abacavir HSR and may allow promotion of abacavir/lamivudine to preferred.

Retrospective case-control studies identified HLA-B*5701, together with some linked alleles, as closely associated with abacavir HSR, and a molecular mechanism for this association has been described.15 Retrospective studies suggested that the test may have a negative predictive value for HSR approaching 100%. Several cohort studies have been reported that suggest that the prospective use of HLA-B*5701 testing may have a significant impact on the observed HSR event rate with abacavir.16

Prospective use of this test was introduced to the Chelsea & Westminster Hospital in London in August 2005. The experience of the first 11 months of this program was compared with a retrospective case note review of all persons beginning therapy with abacavir during the past 12 months.17 Over the first 11 months of testing, 739 tests were performed with only 4 test failures.

Fifty-four (7.3%) of 735 tests were HLA-B*5701-positive, with similar rates observed in men and women. Positive tests were reported in persons classified as white (7.6%, n = 523) and as black (9%, n = 134). Two persons who had positive HLA-B*5701 results began abacavir therapy; HSR developed in both. One hundred ninety-nine HLA-B*5701-negative persons began abacavir therapy, 47 as part of their first antiretroviral therapy regimen. Eight persons discontinued abacavir during the first 3 months of treatment, 4 for a suspected HSR, with the signs and symptoms experienced by these persons consistent with abacavir HSR. Two patients agreed to skin-patch testing for abacavir HSR, and 1 person had a positive skin-patch test. Further evaluation of this person is ongoing.

In the year before the introduction of HLA-B*5701 testing, 10 (7.5%) of 134 persons had discontinued abacavir use because of a possible HSR. After the introduction of prospective HLA-B*5701 testing, the event rate was 4 (2%) of 199, a statistically significant reduction in the event rate (P =.03).

While these data are clearly insufficient to change clinical practice or guidelines, the PREDICT-1 study will be the first randomized prospective study to assess the clinical utility of screening for HLA-B*5701 in HIV-1-infected adults.18 The results are expected in 2007. If the investigators find that this testing is useful, it may become the standard of care. Clinicians should note, however, that abacavir HSR can occur in patients who are HLA-B*5701-negative. The value of this test will be in excluding patients at high risk for abacavir HSR, ie, those who are HLA-B*5701-positive; warnings regarding abacavir HSR must still be given to all patients, and the clinician must maintain continued vigilance for abacavir HSR, even when the patient is HLA-B*5701-negative.

Developments in HIV therapeutics continue to occur at a rapid pace. As this is written, the 14th Conference on Retroviruses and Opportunistic Infections is just a few weeks away. One can expect that this conference will bring further information and surprises--some pleasant and some not.

Dr Boyle reports having received grant support from Bristol-Myers Squibb, Gilead Sciences, Pfizer, and Tibotec and speaking fees and honoraria from Bristol-Myers Squibb and Gilead Sciences. Dr Elion reports having received grant or research support from Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Roche Laboratories, Theratechnologies, and Tibotec; consulting fees from Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline; speaking fees from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, and ViroLogic; and honoraria from all of the above. Dr Cohen reports having received consulting fees and grant or research support from Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Roche Laboratories, and Virco Lab; speaking fees from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Pfizer, Roche Laboratories, and Tibotec; and honoraria from all of the above. Dr Moyle reports having received grant or research support from AnorMED, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmith-
Kline, Neurogesx, Theratechnologies, and Tibotec; consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Incyte, Merck, Monogram Biosciences, Pfizer, Roche Laboratories, Tanox, and Tibotec; speaking fees from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Pfizer, Roche Laboratories, and Tibotec; and honoraria from all of the above. No other potential conflict of interest relevant to this article was reported.


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2. Department of Health and Human Services. Adult and adolescent guidelines. Available at: http://aidsinfo.nih.gov/Default.aspx. Revised October 10, 2006. Accessed February 8, 2007.
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4. Pulido F, Arribas J, Moreno S, et al. Similar virologic and immunologic response to efavirenz or lopinavir/ritonavir-based HAART in a large cohort of antiretroviral-naive patients with advanced HIV infection. 8th International Congress on Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Abstract P9.
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6. Ribaudo H, Kuritzkes D, Lalama C, et al. Efavirenz (EFV)-based regimens are potent in treatment-naive subjects across a wide range of pre-treatment HIV-1 RNA (VL) and CD4 cell counts: 3-year results from ACTG 5095 (A5095). XVI International AIDS Conference; August 13-18, 2006; Toronto. Abstract THLB0211.
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8. Eron J Jr, Yeni P, Gathe J Jr, et al. The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial. Lancet. 2006;368:476-482.
9. Malan N, Krantz E, David N, et al. Efficacy and safety of atazanavir-based therapy in antiretroviral naive HIV-1 subjects, both with and without ritonavir: 48-week results from AI424-089. 13th Conference on Retroviruses and Opportunistic Infection; February 5-8, 2006; Denver. Abstract 107LB.
10. Slim J. Saquinavir/r bid vs lopinavir/r bid plus emtricitabine/tenofovir qd in ARV-naive HIV-1 infected patients: GEMINI study. 8th International Congress on Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Oral PL 2.5
11. Smith K, Weinberg W, DeJesus E, et al. Once-daily boosted fosamprenavir (FPV/r) or atazanavir (ATZ/r) with tenofovir/emtricitabine in antiretroviral naive HIV-1 infected patients: 24-week results from COL103952 (ALERT). 8th International Congress on Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Abstract P1.
12. Hicks C, DeJesus E, Sloan L, et al. Efficacy and safety of once-daily boosted fosamprenavir/ritonavir with abacavir/lamivudine fixed dose combination in antiretroviral naive HIV-1 infected patients: 24-week results from COL100758. 8th International Congress on Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Abstract P2.
13. Cooper D, Zajdenverg R, Ruxrungtham K, Chavez RL. Efficacy and safety of two doses of tipranavir/ritonavir versus lopinavir/ritonavir-based therapy in antiretroviral-naive patients: results of BI 1182.33. 8th International Congress on Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Abstract PL13.4.
14. Pozniak A, Gallant J, DeJesus E, et al. Efficacy and safety of tenofovir DF (TDF), emtricitabine (FTC) and efavirenz (EFV) compared to fixed dose zidovudine/
lamivudine (CBV) and EFV through 96 weeks in antiretroviral treatment-naive patients. 8th International Congress on Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Abstract P6.
15. Mallal S, Nolan D, Witt C, et al. Association between the presence of HLA-B*5701, HLA-DR7 and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir. Lancet. 2002;359:727-732.
16. Rauch A, Nolan D, Martin A, et al. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study. Clin Infect Dis. 2006;43:99-102.
17. Waters L, Gritz A, Maitland D, Nelson M. HLA-B5701 testing and abacavir hypersensitivity: a single centre experience. 8th International Congress on Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Abstract PL9.2.
18. Hughes S, Parry-Billings K, Givens N, et al. PREDICT-1: description of a novel randomised prospective study design to determine the clinical utility of prognostic screening for HLA-B*5701 (study CNA106030). 8th International Congress of Drug Therapy in HIV Infection; November 12-16, 2006; Glasgow, UK. Abstract P118.

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