Table of Contents

• Introduction
• Atazanavir Versus Lopinavir/Ritonavir
• Abacavir/Lamivudine Versus Tenofovir/Emtricitabine
• Efavirenz Versus Maraviroc
• Maraviroc Concentrations in the Female Genital Tract
• An Analysis of the Effect of Baseline Factors on Treatment Outcome in ACTG 5142
• The SMART Study Revisited
• Footnotes

Introduction

The Conference on Retroviruses and Opportunistic Infections (CROI) is the most important conference regarding HIV therapeutics in the United States, and I think it is a really important opportunity for us, as the HIV-treating community, to come together. I'm going to share with you some of my impressions from this premier conference. Every CROI is chock-full of a lot of information. The challenge is for each person attending this conference to distill from the mass of oral presentations and posters the most salient data to take home to their clinic, to their practice and to their research.

The one thing about CROI is that it has never disappointed. I think that's true for this year's conference, as well. There are many big studies, but there are also jewels of small studies that can be very instructive.

What I'll do is try to categorize some of the data so that they are a little bit easier to understand. I'll try to create a theme, or a story, when we look at more than one study together.

I'll start with studies of antiretroviral therapy in treatment-naive individuals. There were two important clinical trials that were presented at CROI that help us understand how well one commonly used and popular regimen does against another regimen that is also very popular and commonly used.

Atazanavir Versus Lopinavir/Ritonavir

Click to enlarge For additional slides from this study, click here. For the poster, click here.

The first of these studies is a long-awaited trial that looked at two of the most popular protease inhibitors that we have available, and that are used clinically.¹ One is lopinavir/ritonavir [LPV/r, Kaletra]. The other is atazanavir [ATV, Reyataz] boosted with ritonavir [RTV, Norvir]. Both of these protease inhibitor giants were compared head to head in a very nice, well-powered study containing 883 individuals. Trial participants were also assigned to take tenofovir [TDF, Viread] and emtricitabine [FTC, Emtriva] as part of their regimen. This study was designed as a one-to-one randomization. It was done largely outside of the United States, but there were some centers in the United States. Like most of these studies, the idea was to see which regimen got people down to less than 50 copies/mL after a year of therapy.

This is a non-inferiority study, which means that it is a study attempting to prove that one regimen is not significantly worse than another regimen. Before a study like this is done, there are some parameters established, which are designed to help understand how much of a difference is acceptable in order to be able to say that there's not a big difference between the two study arms. This is a very commonly employed trial design in this type of research.

For atazanavir boosted with ritonavir, we really didn't have a lot of data prior to thisstudy, even though it is considered a preferred initial regimen for antiretroviral-naive persons according to the U.S. Department of Health and Human Services [DHHS] guidelines.² Certainly, we haven't had a lot of data about the combination of tenofovir, emtricitabine and atazanavir boosted with ritonavir in such a setting, in large numbers of people. So this is a wonderful opportunity to see how atazanavir boosted with ritonavir performs, relative to what certainly many consider to be a very potent regimen of lopinavir/ritonavir combined with tenofovir and emtricitabine.

The bottom line was that, after one year, both regimens did fantastically well. In an intent-to-treat analysis, 78% of patients on atazanavir boosted with ritonavir and 76% of those on lopinavir/ritonavir saw their viral loads fall to below 50 copies/mL.¹ As you can see, the difference between those two arms was not great. Non-inferiority was achieved -- meaning that one regimen was not considered inferior to the other. This shows that these two regimens basically perform very similarly.

Similarly, when you look at the proportion of people whose baseline viral load was greater than 100,000, both drugs performed rather well, with 72% to 74% of people achieving a viral load that was less than 50 copies/mL. This is very reassuring data for those of us who do prescribe atazanavir boosted with ritonavir, and have done so almost sort of based on faith.

Interestingly, the trial investigators conducted a type of analysis that I had not previously seen. The analysis looked at trends in virologic response based upon baseline CD4+ cell count. Interestingly, when you looked at the persons who were on atazanavir boosted with ritonavir, it didn't seem to matter if the patients had a baseline CD4+ cell count of less than 50 cells/mm³, or 50 to 100 cells/mm³, or 100 to 200 cells/mm³, or greater than 200 cells/mm³. There was no trend for change in response, based upon baseline CD4+ cell count.

However, in the lopinavir/ritonavir arm, if the patients' CD4+ cell count was lower at baseline, the response seen was less. There are a couple of important things to mention here. One is that this study looked at lopinavir/ritonavir using the old capsule formulation, and not the new tablet formulation. So for the first 48 weeks of the study, people used the old formulation; and that arguably may be less well tolerated than the new formulation. It's conceivable that some of the people in the lower CD4+ cell count strata who didn't respond as well to lopinavir/ritonavir were people who dropped out of the study due to toxicity, and not necessarily due to virologic failure. That's what I pretty much think is the case.

Otherwise, the adverse events were pretty much as you'd expect. There were more cases of jaundice among the patients who got atazanavir boosted with ritonavir. For those who were on lopinavir/ritonavir, there were more gastrointestinal side effects. Again, that might be driving what we saw with the CD4+ cell count trends that were differentiated.

Interestingly, lipid levels increased basically no matter which regimen patients were on. So if there was any sort of wishful thinking that atazanavir combined with ritonavir, tenofovir and emtricitabine doesn't raise lipid levels, that should be debunked right now. You do see increases in lipid levels.

Increases in non-HDL cholesterol levels were greater with lopinavir/ritonavir. So that was something that clearly differentiated the two regimens. There were higher triglyceride levels and higher total cholesterol levels among patients receiving lopinavir/ritonavir, and I don't think that surprises too many people.

I think this was an interesting study. It shows that the atazanavir boosted with ritonavir and the lopinavir/ritonavir arms are both really potent regimens, that people did fantastically well, as is expected with studies of this type nowadays, and that there are some things that might differentiate these drugs in the context of tenofovir and emtricitabine -- namely, their adverse event profile, and also their effect on lipids. I think this allows for more individualization of care. So those who use atazanavir boosted with ritonavir will be reassured. Those who use lopinavir/ritonavir will be reassured. It allows us to at least understand that there is parity here, where as before, we just had to guess about that.

Abacavir/Lamivudine Versus Tenofovir/Emtricitabine

Click to enlarge For additional images from this study, click here.

Another study that I think also is very similar in many ways is the HEAT study.³ This study looked at initial therapy with two regimens, both of which have some traction in terms of popularity and clinical practice.

In one arm, patients were randomized to tenofovir and emtricitabine in fixed-dose combination [TDF/FTC, Truvada], along with lopinavir/ritonavir. The other arm received abacavir [ABC, Ziagen] and lamivudine [3TC, Epivir] in fixed-dose combination [ABC/3TC, Epzicom, Kivexa], along with lopinavir/ritonavir. Importantly, lopinavir/ritonavir was administered once daily. This was a double-blind, placebo-controlled study. Almost 700 people enrolled in this study, and they all had to be treatment naive. The study was mostly done in the United States and Puerto Rico.

The interesting thing about this study, of course, is that there has been this nucleoside battle -- abacavir versus tenofovir -- going on for a number of years. This was a nice way to look at this, head-to-head, and find out what are the differences, if any, between these two regimens.

Again, as we've seen in other trials of very potent regimens, both arms did very well at achieving virologic suppression at 48 weeks. In this study, about 70% of people achieved a viral load of less than 50 copies/mL by week 48 using an intent-to-treat analysis. This is a little bit less than we've seen in other studies, but it's hard to compare from study to study. Importantly, CD4+ cell count increases were very similar in both arms. There really wasn't much to differentiate between these two drugs.

If you look at the resistance that developed among patients in this trial, again, there were not too many cases of virologic failure. So we're not talking about great numbers, but of the patients who did develop identifiable resistance mutations, the researchers reported 14 cases of M184V or mixtures of mutations in the tenofovir/emtricitabine arm, compared to seven in the abacavir/lamivudine arm.

This is an unusual way to present these data and I'm not really sure exactly what they mean. There is some buzz at the conference that these mixtures, of course, include non-M184V mutations, meaning other types of mutations at that same codon -- for instance, M184I, which can confer resistance to emtricitabine and lamivudine, and even M184A. There is still a little controversy about whether M184A really does lead to resistance to those two drugs. So this has to be fleshed out. Unfortunately, this presentation didn't enumerate and describe these mixtures very well. We have to take that with a grain of salt right now, and not be too concerned about it.

Otherwise, these two regimens were quite identical in most regards.

Fortunately, in this trial, hypersensitivity reactions were fairly rare. There was a pretty aggressive strategy for identifying reports of abacavir hypersensitivity reaction. A clinician would then follow up by contacting the sites to confirm the reactions and discuss them. That helped a lot in keeping the actual hypersensitivity reaction rate fairly low, with only 4% of the persons who were in the abacavir arm being diagnosed with abacavir hypersensitivity reaction. HLA-B*5701 testing was not done in this study.

Overall, I think that this is reassuring. We see that these two regimens perform very well, and that this, again, adds to some confidence regarding the use of either drug. Recently, abacavir was added to the DHHS guidelines as a preferred nucleoside for initial therapy.² Certainly, this study adds a little bit of weight to that recommendation.

There are other data about abacavir that we'll talk about in a little bit that I think are also interesting in the context of this study and the DHHS recommendations. But this is, I think, an important comparison.

Efavirenz Versus Maraviroc

Another category of trials that I think is interesting to think about are the protocols that have already been completed, but are now being revisited. The purpose of doing these secondary analyses is to understand the results that were obtained. In the specific case of the MERIT trial, this study compared efavirenz [EFV, Sustiva, Strocin] to maraviroc [MVC, Selzentry, Celsentri] in people also receiving zidovudine/lamivudine [AZT/3TC, Combivir].

This was a very interesting study, because maraviroc is an exciting compound. It is a CCR5 antagonist. Many people are interested in looking at CCR5 antagonists early in the course of HIV therapy, because that's when virus that is tropic for CCR5 is more dominant.

In this study, which has been presented previously, a large number of patients were studied for at least 48 weeks.⁴ What was the surprise story from this particular trial was that, when you looked at the numbers of patients who achieved a viral load of less than 400 copies/mL, which was the primary endpoint, maraviroc and efavirenz were equivalent, and that was reassuring.

However, when you looked at the numbers of patients who achieved a viral load of less than 50 copies/mL, which was, admittedly, a secondary endpoint, there was a difference and non-inferiority was not achieved. Maraviroc was thus considered not to be non-inferior to efavirenz, since 65.3% of people who were randomized to maraviroc and zidovudine/lamivudine achieved a less than 50-copies/mL viral load at that time point, compared to almost 70% of patients who received the combination of zidovudine/lamivudine and efavirenz.

Click to enlarge

The investigators who ran that trial were very interested in understanding these results, and so they conducted a series of analyses to try to better understand the data.⁵

What they looked at specifically was the tropism of the virus among people who were in the study. Everyone was screened, of course, to be R5. Patients had to have a Trofile test and it had to indicate that they had only R5 virus. We know from several studies now that the timeframe can have a big effect on what happens subsequent to that screening test.

Specifically, we know that for a percentage of people whose screening test shows R5 virus, by the time they enter a study they will have already developed a non-R5-tropic virus, meaning they could have a dual or a mixed population, or even an R4 virus. Now, whether this is a progression or an evolution of the virus within their bodies in this short period of time, or whether the test initially did not pick up the R4 or dual/mixed populations, is not completely clear. But it seems it's more likely the latter than the former.

In the MERIT study, 25 people, almost 4% of the population studied, had a dual/mixed viral population at baseline. This means they had both R4- and R5-tropic virus, even though they had screened for R5 only earlier. So when you look at these folks, they are different.

In people who were strictly R5 at screening and baseline, there was no difference seen between the maraviroc and efavirenz as far as getting viral loads to less than 50 copies/mL at 48 weeks. However, when you look at the people who had the dual/mixed viral population, 54.6% of the patients who were taking efavirenz were able to get to undetectable, compared to only 7.1% of those who were on maraviroc.

The bottom line: It kind of goes in the "duh" category that, if patients have dual/mixed-tropic virus -- in other words, if they don't have purely R5-tropic virus -- maraviroc is just not going to work. That's a really important lesson for us, and it may help us understand the MERIT results and help us understand that these two drugs, in people who truly do have R5 virus only, are probably not much different.

Another component of the study that was presented at CROI examined the lipid profile of patients who received maraviroc versus those who received efavirenz in the MERIT study.⁶ As has been reported previously,^7,8 it looks like maraviroc does not have much of an adverse lipid profile and we certainly have accumulating data⁹ that indicate that efavirenz plus two nucleosides does have an impact.

Reassuringly, we see that in this treatment-naive study maraviroc really had minimal impact on triglyceride levels, and levels of LDL and HDL cholesterol. The analysis that was done that I think is most interesting is that when you look at people who had at baseline elevated lipid levels -- in this case, LDL -- those who were taking efavirenz experienced even greater increases in their LDL levels, compared to those who received efavirenz who had lower a LDL level at baseline. In contrast, in patients taking maraviroc, you actually saw a trend towards the opposite, where no matter what the patients' LDL level was at baseline, you didn't see much of a gain. If anything, in the few people who had a high LDL level at baseline, we saw an actual decrease in their LDL level after they started on maraviroc.

So, nice data indicating that probably the potency is there, where as before we weren't able to fully comprehend that since the tropism of the patient's virus was not known at the time he or she entered the study and began taking maraviroc. Regarding the lipid profile: again, these are additional data that help us understand that maraviroc is probably a fairly lipid-friendly drug.

Maraviroc Concentrations in the Female Genital Tract

Click to enlarge For additional slides from this study, click here.

Maraviroc has some other characteristics that might make it more attractive in other settings than the salvage setting. Particularly, there was a very nice study on maraviroc concentrations in the vaginal fluid of women who were receiving it.¹⁰ Comparing those concentrations to those of other drugs, we see that maraviroc really does seem to concentrate in the genital tract.

There was a 400% increase in the concentration of maraviroc in the vaginal fluid, compared to that in blood plasma. When you look at other HIV drugs, very few even come close to this.¹¹ Lamivudine does, but most other drugs achieve half the vaginal concentration level of maraviroc. Indinavir [IDV, Crixivan], maraviroc as mentioned, lamivudine and emtricitabine concentrate in the vaginal fluid, , but there are many drugs, such as many of our protease inhibitors, whose concentration in the vaginal fluid is a fraction of their concentration in blood plasma. Lopinavir [LPV], atazanavir, saquinavir [SQV, Invirase], ritonavir and amprenavir [APV, Agenerase] have lower concentrations in the cervical vaginal fluid than they do in blood plasma.

This opens up the possibility of using maraviroc in situations in which you would want to have a lot of drug present in the vaginal fluid, for instance, as a sexual post-exposure prophylaxis, or even as a pre-exposure prophylaxis. This is really intriguing data that open up avenues for further investigation.

An Analysis of the Effect of Baseline Factors on Treatment Outcome in ACTG 5142

In the same vein, another analysis conducted of a previously reported study was a presentation on ACTG 5142. This is a very famous study -- well known, well reported -- that compared efavirenz versus lopinavir/ritonavir, both with two nucleosides, versus a third arm that included lopinavir/ritonavir and efavirenz together, sparing nucleosides. I think that everyone who is reading this appreciates that ACTG 5142 was a hallmark study that was particularly notable for its finding that efavirenz produced better virologic responses, while lopinavir/ritonavir yielded increased CD4+ cell count gains over efavirenz,¹² and that the metabolic profiles of these drugs were not that dissimilar.⁹ In fact, if anything, in the efavirenz arm of the study, we saw more lipoatrophy.

Click to enlarge

So, a very important study. What the investigators of ACTG 5142 did now is go back to the data to try to determine which kind of patient is more likely to not do well on these regimens.¹³

They analyzed a bunch of different factors. They found that virologic failure was more likely to occur in people who had a lower CD4+ cell count at baseline, as well as among African Americans, those who were younger, and those who were female. The trend towards women not doing as well was pretty slight. It just achieved statistical significance. That's important, because several other studies have shown that women actually do better virologically in clinical trials.^14,15

Click to enlarge

However, many studies have also indicated that African Americans don't do as well, either in the clinic or in clinical trials.^16,17 So I think this reaffirms that this is occurring and, again, lends credence to the idea that we have to really think hard about what's going on among African-American study participants and patients in order to explain why they are not doing as well as persons of other races and ethnicities.

In this analysis of ACTG 5142, women had a longer time to virologic failure, however, and treatment-limiting toxicity, when they were taking the lopinavir/ritonavir and efavirenz together. These are people who did not get nucleosides. This suggests that perhaps women are more susceptible to nucleoside-related toxicities. That has been suggested in other studies, and I think it's very interesting -- not that we're going to use the data to say that we shouldn't give nucleosides to women. It just indicates that there is likely to be more toxicity to that particular class of drugs occurring in women than men.

In all three regimens, patients achieved a CD4+ cell count over 200 cells/mm³ in similar time, even among those who had a baseline CD4+ cell count of less than 50 cells/mm³. Again, women were more likely to experience or report symptoms, though the proportion of men and women with treatment-limiting toxicity overall in this study was very similar.

I don't think there's anything in this study that's going to help us in determining which patients should be given which therapy, but I do think it raises some red flags, particularly with regards to the racial differences that were seen. In addition, we are reminded that we have to be very careful when we analyze these studies and make sure that we take into account gender differences in outcomes.

The SMART Study Revisited

Last in this series of studies that we're looking at in which investigators revisited their data to try to make heads and tails of what they found, is the SMART study. I've argued, as many have, that this is one of the most important trials that has ever been conducted in the field of HIV. Most of the people reading this are very well aware of the study design and the results: namely, that this was a strategy study, looking at continuing on antiretroviral therapy for patients who had largely already begun antiretroviral therapy, versus the strategy of conserving patients' exposure to antiretrovirals by performing intermittent treatment interruptions, guided by CD4+ cell count, such that when the CD4+ cell count rose to more than 350 cells/mm³, antiretroviral therapy would stop. When the CD4+ cell count dropped below 250 cells/mm³, therapy would be reinitiated.¹⁸

The study enrolled more than 5,400 people across the planet. It was stopped early, with only 16 months of follow-up, when it became very clear during a Data and Safety Monitoring Board review that the strategy of drug conservation -- or intermittent treatment interruptions -- was leading to more adverse outcomes, including mortality, as well as other morbidity, including cardiovascular disease, renal disease and hepatic disease, when compared to those who continued on HIV therapy. This really put the nail in the coffin for treatment interruptions subsequently.

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The investigators from the SMART study have continued to work hard to try to find out exactly what was going on in this study. In addition, they have been able to continue to follow participants in the study to understand what's gone on after the study was modified and stopped, back in January of 2006.¹⁹

Very soon after the news of the stopping of the study was released, the majority of people on the drug discontinuation arm were started on HIV therapy. So by three months, about 70% of those people were now on antiretroviral therapy. At 18 months, 84% were now on HIV therapy. This compares to the continuous therapy arm, which maintained about 95% HIV treatment rates throughout the course of this study.

Click to enlarge

This is an opportunity to look at what happens when you take somebody who was basically doing OK on his or her HIV therapy, stop it, and then, after a period of time, restart it again. Are there any lasting effects of that treatment interruption? This is a major question that I think can now be answered, given the follow-up time.

The answer is that there is some residual damage from the interruption. Even though the rates of HIV therapy in the two groups at the end of 18 months are not exactly superimposable, we do see that, among the patients who are getting treated, there are some residual problems with maintaining a CD4+ cell count climb.

Specifically, among the patients who are in SMART and discontinued their therapy, those who even achieved a viral load of less than 400 copies/mL after reinitiating their therapy just cannot seem to get the same kind of responses that they had before. The percentage of patients with a viral load less than 400 copies/mL, and those who have a CD4+ cell count that is increased, is different between the two study arms and this persists out to 18 months.

At the 18-month time point, 84% of people who were maintained on HIV therapy in the viral suppression arm had a viral load of less than 400 copies/mL, compared to only 73% of those in the discontinuation arm. Similarly, when you look at the mean CD4+ cell counts between the two arms, it was 648 cells/mm³ among those who maintained HIV therapy, versus 507 cells/mm³ among those who had stopped and largely had reinitiated therapy by the time that this analysis was done.

I think that these are sobering data. There is some reversal of what had gone on when therapy was stopped, however, there does seem to be some lingering problems with patients who had interrupted therapy achieving a viral load of less than 400 copies/mL and/or being able to manifest an increase in CD4+ cell count as you would expect to have had if therapy was maintained. So this study continues to provide a lot of intriguing data, and I think it really does make it clear that treatment interruptions are to be avoided, especially lengthy ones as was seen in this particular trial.

This transcript has been edited for clarity.

Footnotes

1. Molina J-M, Andrade-Villanueva J, Echevarria J, et al. Efficacy and safety of once-daily atazanavir/ritonavir compared to twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine in ARV-naive HIV-1-infected subjects: the CASTLE study, 48-week results. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 37.
   View poster: Download PDF
   View slides: Download PDF
2. The DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Office of AIDS Research Advisory Council, US Dept of Health and Human Services; January 29, 2008.
3. Smith K, Fine D, Patel P, et al. Efficacy and safety of abacavir/lamivudine compared to tenofovir/emtricitabine in combination with once-daily lopinavir/ritonavir through 48 weeks in the HEAT study. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 774.
   View poster: Download PDF
4. Saag M, Ive P, Heera J, et al. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine [ZDV]/lamivudine [3TC]), for the treatment of antiretroviral naive patients infected with R5 HIV 1: week 48 results of the MERIT study. In: Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Abstract WESS104.
   View slides: Download PowerPoint
5. Heera J, Saag M, Ive P, et al. Virological correlates associated with treatment failure at week 48 in the phase 3 study of maraviroc in treatment-naive patients. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 40LB.
6. DeJesus E, Walmsley S, Cohen C, et al. Fasted lipid changes after administration of maraviroc or efavirenz in combination with zidovudine and lamivudine for 48 weeks to treatment-naive HIV-infected patients. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 929.
   View poster: Download PDF
7. Lalezari J, Goodrich J, DeJesus E, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results of a phase 2b/3 study in the US and Canada. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Abstract 104bLB.
8. Nelson M, Fätkenheuer G, Konourina I, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1 in Europe, Australia, and North America: 24-week results. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Abstract 104aLB.
9. Haubrich RH, Riddler S, DiRienzo G, et al, and the AIDS Clinical Trials Group 5142 Study Team. Metabolic outcomes of ACTG 5142: a prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Abstract 38.
10. Dumond J, Patterson K, Pecha A, et al. Maraviroc (MVC) pharmacokinetics (PK) in blood plasma (BP), genital tract (GT) fluid and tissue in healthy female volunteers. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 135LB.
    View slides: Download PDF
11. Min SS, Corbett AH, Rezk N, et al. Protease inhibitor and nonnucleoside reverse transcriptase inhibitor concentrations in the genital tract of HIV-1-infected women. J Acquir Immune Defic Syndr. December 15, 2004;37(5):1577-1580.
12. Riddler SA, Haubrich R, DiRienzo G, et al, and AIDS Clinical Trials Group 5142 Study Team. A prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection -- ACTG 5142. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract THLB0204.
    View slides: Download PowerPoint
13. Riddler S, Haubrich R, DiRienzo G, et al, and AIDS Clinical Trials Group 5142 Study Team. Effect of baseline characteristics on treatment outcomes in ACTG 5142: a prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 776.
14. Collazos J, Asensi V, Carton JA, for the Grupo Espanol para el Estudio Multifactorial de la Adherencia (GEEMA). Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART. AIDS. April 23, 2007;21(7);835-843.
15. Nicastri E, Leone S, Angeletti C, et al. Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review. J Antimicrob Chemother. October 2007;60(4):724-732.
16. Schackman BR, Ribaudo HJ, Krambrink A, Hughes V, Kuritzkes DR, Gulick RM. Racial differences in virologic failure associated with adherence and quality of life on efavirenz-containing regimens for initial HIV therapy: results of ACTG A5095. J Acquir Immune Defic Syndr. December 15, 2007;46(5):547-554.
17. Anastos K, Schneider MF, Gange SJ, et al, for the Women's Interagency HIV Study Collaborative Group. The association of race, sociodemographic, and behavioral characteristics with response to highly active antiretroviral therapy in women. J Acquir Immune Defic Syndr. August 15, 2005;39(5):537-544.
18. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. November 30, 2006;355(22):2283-2296.
19. El-Sadr W and SMART Study Group. Re-initiation of ART in the CD4-guided ART interruption group in the SMART study lowers risk of opportunistic disease or death. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 36.