Treating Antiretroviral-Naïve HIV-1 Infected Patients

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Treating AntiretroviralNa誰ve HIV-1 Infected Patients Also Inside:

Overcoming Challenges in HIV Therapy Stacking the Deck Against HIV Considering Gender Differences in HIV

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Data from the CASTLE study indicate that atazanavir sulfate/ritonavir has non-inferior antiviral efficacy as compared with lopinavir/ritonavir. Response rates were comparable between the regimens regardless of the qualifying viral load.

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ntiretroviral therapy for patients with HIV is intended to improve and/or preserve immune function and reduce HIV-associated morbidity and mortality. According to guidelines from the Department of Health and Human Services (DHHS), which were updated November 3, 2008, antiretroviral therapy should be initiated in patients with a history of an AIDS-defining illness or with a CD4+ T-cell count less than 350 cells/mm3. The data supporting this recommendation are stronger for those with CD4+ T-cell counts of less than 200 cells/mm3 and with a history of AIDS than for those with CD4+ T-cell counts between 200 cells/mm3 and 350 cells/mm3.

The updated DHHS guidelines note that antiretroviral therapy should also be initiated in pregnant women, patients with HIV-associated nephropathy, and patients coinfected with hepatitis B virus when treatment is indicated, regardless of CD4+ T-cell count. The guidelines also recommend that antiretroviral therapy be considered in some patients with CD4+ T-cell counts higher than 350 cells/ mm3.

Discuss Adherence to Drug Regimens Patient commitment to life-long therapy is an important factor to consider when discussing treatment with patients infected with HIV, especially those who are treatment-na誰ve. The DHHS guidelines recommend that patients and clinicians have in-depth discussions about the necessity for patient adherence to long-term drug regimens. Potential barriers to adherence should be identified and addressed before therapy is initiated.

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Several factors should be taken into consideration when selecting drug regimens (Table 1), and clinicians are recommended to establish potential influences on decisions for treatment-naïve patients. The DHHS guidelines note that regimen selections should be individualized based on patient characteristics. Clinicians should also seize opportunities to discuss initiation of prophylactic medications for opportunistic infections associated with HIV.

Indications for Atazanavir Sulfate Atazanavir sulfate is a protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. The indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from controlled studies of 48 weeks duration in antiretroviral-naïve and antiretroviral-experienced adult and pediatric patients (aged 6 and older).

DHHS: Factors to Consider When Selecting an Initial Regimen Table 1

Regimen selection should be individualized, taking into consideration a number of factors, including: • Comorbidity or conditions such as tuberculosis, liver/renal disease, psychiatric disease, cardiovascular disease, and chemical dependency • Patient adherence potential • Dosing convenience, including pill burden, dosing frequency, and food/fluid considerations • Potential drug interactions with other medications • Pregnancy or pregnancy potential • Results of genotypic drug resistance testing • Gender and pretreatment CD4+ T-cell count if considering nevirapine • HLA B*5701 testing if considering abacavir Source: DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, November 3, 2008. Available at: www.aidsinfo.nih.gov/ contentfiles/AdultandAdolescentGL.pdf. Accessed March 18, 2009.

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CASTLE Data In the August 23, 2008 issue of The Lancet, data from the CASTLE study were published. It was an openlabel, randomized, 96-week, non-inferiority study to determine the comparative clinical efficacy and safety of atazanavir sulfate/ritonavir and lopinavir/ritonavir regimens in treatment-naïve HIV-1-infected adult patients. Patients were required to have a screening HIV1 RNA of ≥5,000 copies/mL, and there was no CD4+ cell-count restriction. A total of 883 patients were randomized, 440 to atazanavir sulfate/ritonavir and 443 to lopinavir/ritonavir. Baseline characteristics were well balanced between the regimens. About 31% of patients were female and 4% to 5% had a pre-existing AIDS diagnosis. The median baseline viral load was about 5 log10 copies/mL; approximately one half of the patients had viral loads ≥100,000 copies/mL. The median CD4+ count was about 200 cells/mm3 with about 12% having <50 cells/mm3. Most patients (66%) were infected with HIV subtype B.

Primary Efficacy Endpoint: ITTConfirmed Virologic Response (NC=F) Figure 1

Percentage of Respondents (SE)

100 80

Atazanavir sulfate/ritonavir regimen (n=440) Lopinavir/ritonavir regimen (n=443)

60

HIV-1 RNA <50 copies/mL (78% atazanavir sulfate/ritonavir vs 76% lopinavir/ritonavir)

40

Estimated difference: 1.7% (95% CI, -3.8% to 7.1%)

20 0

As treated analysis: HIV-1 RNA <50 copies/mL* Atazanavir sulfate/ritonavir 78%, Lopinavir/ritonavir 77% (n=441 and 437, respectively)*

Baseline 4

12

24

36

48

Weeks Atazanavir sulfate/ritonavir regimen has non-inferior antiviral activity compared with lopinavir/ritonavir regimen.

Supporting Analyses: • ITT-TLOVR: HIV-1 RNA <50 copies/mL: atazanavir sulfate/ritonavir 78%, lopinavir/ritonavir 76%, 1.9% (95% CI, -3.6% to 7.4%) * REYATAZ Full Prescribing Information.

250 m3)

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Source: Molina JM, et al. Lancet. 2008;372:646-655.

Atazanavir sulfate/ritonavir regimen (n=440) Lopinavir/ritonavir regimen (n=443)

The CASTLE study demonstrated durable virologic suppression and safety of an atazanavir sulfate/ritonavir-based regimen in treatment-na誰ve patients.

In the CASTLE study, the dosing regimen for the comparator groups was atazanavir sulfate/ritonavir 300/100 mg once daily or lopinavir/ritonavir 400/100 mg twice daily (BID), both given with fixed-dose TDF/ FTC 300/200 mg once daily. Lopinavir/ritonavir was given as capsules through Week 48; the lopinavir/ritonavir tablet was allowed in the second year of the study where available commercially.

Comparable Efficacy & Safety The CASTLE study demonstrated durable virologic suppression and safety of an atazanavir sulfate/ritonavirbased regimen in treatment-na誰ve patients. The primary endpoint of the study was an intention-to-treat (ITT) confirmed virologic response (CVR). As assessed by the principal analysis of the ITT-CVR analysis, atazanavir sulfate/ritonavir was shown to have non-inferior antiviral efficacy compared with lopinavir/ritonavir (Figure 1). According to the CVR endpoint, 78% of patients in the atazanavir sulfate/ritonavir group achieved an HIV-1 RNA of less than 50 copies/mL compared with 76% of patients in the lopinavir/ritonavir group (estimated difference, 1.7%; 95% CI, -3.8 to 7.1). This was confirmed by the supportive analyses using an ITT analysis based on time to loss of virologic response with the primary endpoint of an HIV-1 RNA of <50 copies/mL. According to CASTLE data, response rates were comparable between atazanavir sulfate/ritonavir regimens and lopinavir/ritonavir regimens, regardless of the qualifying viral load. For patients with HIV RNA <100,000 copies/mL, the response rates were 82% and 81% for atazanavir sulfate/ritonavir and lopinavir/ritonavir,

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70

Percentage of Respondents (<50 c

ity

60 50

ITT-CVR (NC=F) by Qualifying HIV Viral Load

vir 78%,

Figure 2

100

HIV RNA <100,000 copies/mL

Percentage of Respondents (<50 copies/mL)

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cells/mm3: onavir) and avir)

82%

30 20

HIV RNA ≥100,000 copies/mL

10

81%

80

74%

0

72%*

70

217

n=

60

Atazanavir sulfate/rit

50

*As treated values: n=222,

40 30 20 10 0

n=

217

218

223

Atazanavir sulfate/ritonavir regimen

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40

225

Lopinavir/ritonavir regimen

*As treated values: n=222, percent responders=73%.

cells/mm3

Sources: Molina JM, et al. Lancet. 2008;372:646-655. REYATAZ Full Prescribing Information.

Figure 3

Response Rate by Baseline CD4+ Cell Co

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78%

6%

80%

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78%

76%

75%

70 60 50 40 30

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10 0

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Percentage of Respondents (<50 copies/mL)

Percentage of Respondents (<50 copies/mL)

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80%

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106

78%

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60 Atazanavir sulfate/ritonavir regimen

58

69%

50 3 ≥200 cells/mm

50-<100 cells/mm3

100-<200 cells/mm3

<50 cells/mm3

40

63%

A direct comparison of efficacy within each 30 CD4+ cell-count subgroup cannot be made between the two regimens because the study was not designed for such an analysis.

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58

r regimen

20 10 0

n=

228

134

29

48

Lopinavir/ritonavir regimen

50-<100 cells/mm3

≥200 cells/mm3

50-<100 cells/mm3

<50 cells/mm3

100-<200 cells/mm3

<50 cells/mm3

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70

60

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respectively (Figure 2). In patients with HIV RNA â&#x2030;Ľ100,000 copies/mL, the corresponding rates were 74% and 72%, respectively. In addition, response rates across baseline CD4+ cell count subgroups were consistent with the primary endpoint for those patients on an atazanavir sulfate/ritonavir regimen (Figure 3).

40

30

20

10 0

n=

217

218

223

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Both the atazanavir sulfate/ritonavir and lopinavir/ritoAtazanavir sulfate/ritonavir regimen Lopinavir/ritonavir regimen navir regimens were also associated with an increase in eated values: n=222, percent responders=73%.

CD4+ cell counts from baseline through Week 48 (Figure 4). The mean increase at Week 48 was 203 cells/ mm3 in the atazanavir sulfate/ritonavir regimen and 219 cells/mm3 in the lopinavir/ritonavir regimen.

Treatment Efficacy & Gender Findings from the CASTLE study also demonstrated that the efficacy of treatment with either atazanavir sulfate/ritonavir or lopinavir/ritonavir regimens was similar for both men and women involved in the study.

Virologic response rates and mean CD4+ cell count

ount 100 Percentage of Respondents (<50 copies/mL)

90 80%

80

78% 69%

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63%

60 50 40 30 20 10 0

n=

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134

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Lopinavir/ritonavir regimen â&#x2030;Ľ200 cells/mm3

50-<100 cells/mm3

100-<200 cells/mm3

<50 cells/mm3 Source: Molina JM, et al. Lancet. 2008;372:646-655.

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Figure 4

CD4+ Mean Change

CD4+ Mean Change (cells/mm3)

250 200

Atazanavir sulfate/ritonavir regimen (n=440) Lopinavir/ritonavir regimen (n=443)

150 Increase in mean CD4+ cells/mm3: 203 (atazanavir sulfate/ritonavir) and 219 (lopinavir/ritonavir)

100 50 0

Baseline 4

12

24

36

48

Weeks The median increase from baseline in CD4+ cell count was 191 cells/mm3 for the atazanavir sulfate/ritonavir arm and 200 cells/mm3 for the lopinavir/ritonavir arm.

Source: Molina JM, et al. Poster #37 presented at CROI 2008.

Addressing Adverse Events

Percentage of Respondents (<50 copies/mL)

change were consistent with the overall study population for both male and female patients. For patients receiving an atazanavir sulfate/ritonavir regimen, 76% of women and 79% of men had HIV RNA levels of less than 50 copies/mL at Week 48. For those receiving a lopinavir/ritonavir regimen, 73% of women and 78% of men had HIV RNA levels of <50 copies/mL at Week 48. The average CD4+ cell-count change from baseline was also similar for both men and women.

The CASTLE study results reflect demonstrated tolerability and safety, with a low incidence of discontinuation due to adverse events (AEs) for an atazanavir sulfate/ritonavir regimen in treatment-na誰ve patients.

Serious AEs and Grade 2-4 treatment-emergent AEs were summarized in the CASTLE study and included events of possible, probable, certain, or unknown relationship to the treatment regimen selected. Grade 2-4 jaundice occurred in 4% of atazanavir sulfate/ritonavir patients and in no lopinavir/ritonavir patients. Nausea was found in 4% of the atazanavir sulfate/ritonavir group and 8% for lopinavir/ritonavir patients. Diarrhea occurred in 2% of atazanavir sulfate/ritonavir recipients and 11% of those receiving lopinavir/ritonavir. Rash occurred in 3% and 2% of atazanavir sulfate/

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100 90

8

80 70 60 50 40 30 20 10 0

n=

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ritonavir and lopinavir/ritonavir patients, respectively.

One discontinuation due to a renal AE occurred in each treatment regimen arm; Fanconi syndrome occurred in the atazanavir sulfate/ritonavir arm and proteinuria occurred in the lopinavir/ritonavir arm. Adverse events within gender subgroups were generally consistent with the overall study population.

Data have also studied select Grade 3-4 laboratory abnormalities with use of atazanavir sulfate/ritonavir and lopinavir/ritonavir regimens. Total bilirubin elevations occurred more frequently in the atazanavir sulfate/ritonavir arm, with 34% of patients having 2.6 Ă&#x2014;ULN bilirubin or higher. Clinicians are recommended to review the rates of elevations in transaminases, total cholesterol, and triglycerides as reported. Also of note was the change from baseline at 48 weeks in renal function: the mean change in serum creatinine was 0.5 mg/L of less for both regimens and the median calculated creatinine clearance was a 1% decrease in both regimens. Laboratory abnormalities within gender subgroups were generally consistent with the overall study population.

In addition, lipid profiles for both atazanavir sulfate/ ritonavir and lopinavir/ritonavir regimens have also been described. The atazanavir sulfate/ritonavir regimen had a low impact on lipids, but it should be noted that the clinical impact of these findings has not been demonstrated, and values obtained after initiation of lipid-lowering agents were not included.

Information on Patient Counseling When prescribing medications, clinicians should inform their patients that these drugs are not a cure for HIV infection, and patients may continue to develop opportunistic infections and other complications associated with HIV disease. There are currently no data demonstrating that therapy with atazanavir sulfate/ ritonavir and lopinavir/ritonavir combination therapy can reduce the risk of transmitting HIV to others through sexual contact.

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Patients should also be counseled about dosing instructions with combination therapies for HIV, drug interactions, and risks for cardiac conduction abnormalities, rash, hyperbilirubinemia, and fat redistribution.

An understanding of drug-drug interactions between protease inhibitors and hormonal contraceptives, such as ethinyl estradiol and norgestimate or norethindrone, is also important. Last but not least, patients should be reminded about how they should take their HIV medications. These therapies should be taken exactly as prescribed, with consideration to taking them with food and at specific times during the day. Patients should be instructed to continue their medications as directed and educated on what to do if doses are missed.

Readings and Resources Panel on Antiretroviral Guidelines for Adults and Adolescents.

Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.

November 3, 2008; 1-139. Available at www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed March 18, 2009.

Molina JM, Andrade-Villanueva J, Echevarria J, et al; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study.

Lancet. 2008;372:646-655. Available at: www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61081-8/fulltext.

REYATAZ Full Prescribing Information. Available at: http://packageinserts.bms.com/pi/pi_reyataz.pdf.

Molina JM, Andrade-Villanueva J, Echevarria J, et al. Efficacy and safety of once-daily atazanavir/ritonavir compared to twicedaily lopinavir/ritonavir, each in combination with tenofovir and emtricitabinein ARV-naive HIV-1-infected subjects: the CASTLE study, 48-week results. Conference on Retroviruses and Opportunistic Infections. Boston, Massachusetts; February 3-6, 2008: Poster #37.

Available at: www.retroconference.org/2008/Abstracts/31137.htm.

Absalon J, Uy J, Yang R, Mancini M, McGrath D. Gender-based differences in ARV-na誰ve patients treated with boosted protease inhibitors (PIs): results from the CASTLE study (AI424138). XVII International AIDS Conference. Mexico City, Mexico; August 3-8, 2008: Poster TUPE0062.

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Overcoming Challenges in HIV Therapy Eric S. Daar, MD Chief, Division of HIV Medicine Los Angeles Biomedical Research Institute at Harbor-UCLA Professor of Medicine David Geffen School of Medicine at UCLA

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ver the past few years, HIV treatment regimens have continued to improve, and the number of options and overall antiviral activity of these options is higher than ever. The likelihood of patients achieving undetectable levels of HIV and preventing the emergence of drug-resistant virus is also at an all-time high. Based on clinical trial data and clinical experience, the current expectation is that approximately 80% of patients starting therapy for the first time will achieve undetectable levels of HIV within a few months of initiating treatment and are likely to sustain viral suppression over many years.

Unprecedented advances in HIV have occurred over the past year, including the development of new drugs and the emergence of new data for managing treatmentexperienced patients. Several new medications that were developed for treatment-experienced patients with multidrug-resistant virus have become available; theyâ&#x20AC;&#x2122;re providing new treatment options for patients with highly drug-resistant virus and/or intolerance to previously available agents.

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Tolerability & Virologic Failure Although the tolerability of antiretroviral drugs varies from person to person, currently available HIV treatment regimens are generally easy to take and well tolerated. Clinicians have historically made efforts to address tolerability but were left with the decision to either have their patients deal with these drug side effects or not be treated. For­tunately, newer treatment options have minimized the effect of tolerability concerns.

Although no single regimen will be tolerable by every patient, clinicians who work closely with their patients are more likely than ever to find an effective regimen with minimal side effects. When one regimen is intolerable, clinicians can now offer several different options without the potential for the development of multidrug-resistant virus. It should be noted that when tolerability issues become severe, virologic failure may result. Clinicians need to assess the reason behind the virologic failure so that appropriate treatment adjustments can be made.

Patients with tolerability issues often won’t take their HIV medications as directed because the side effects are too great a burden. In addition, they may miss doses for a variety of other reasons, such as having an important meeting at work or attending a social function. In other scenarios, underlying psychiatric, social problems or drug abuse can reduce adherence to medications.

Regardless of the circumstances, the key for clinicians is to talk openly with patients before and during treatment. It’s critical to find out about the patient’s personal situation and circumstances before therapy is initiated.

Patients also need to understand that available treatment options may help them overcome some of their life obstacles.

Individualize Approaches Clinicians should strive to identify patients at

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risk for tolerability issues or poor adherence before initiating therapy in order to reduce the risk for developing multidrug-resistant virus while on therapy. This requires having a regular dia­logue with patients; they should be informed about the efficacy of therapy and cautioned that no one regimen is perfect for everyone. It’s critical to get “buy in” from patients; they need to believe that their provider will listen to them, work with them, and make changes to treatment regimens if necessary. A greater emphasis should also be made to have patients understand the goals of therapy. We’re aiming to provide them with therapies that they’ll completely tolerate on a regular basis to achieve undetectable levels of virus.

To achieve long-term success, establishing individualized approaches and carefully balancing tolerability with efficacy and the potential for drug resistance are paramount.

Financial Disclosure Statement Eric S. Daar, MD, has indicated to Physician’s Weekly that he has received grants and/or research support from Abbott, Boehringer Ingelheim, Gilead, GlaxoSmithKline, and Merck. He has also disclosed that he has served on the speaker’s bureau for and/ or served as a consultant to Abbott, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Pfizer, Tibotec,Pathway Diagnostics, Oncolysis and Monogram.

Readings and Resources Hammer SM, Eron JJ Jr, Reiss P, et al. International AIDS SocietyUSA. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel.

JAMA. 2008;300:555-570.

Lagnese M, Daar ES. Antiretroviral regimens for treatmentexperienced patients with HIV-1 infection. Expert Opin Pharmacother. 2008;9:687-700.

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Stacking the Deck Against HIV Joel E. Gallant, MD, MPH Professor of Medicine and Epidemiology Division of Infectious Diseases Johns Hopkins University School of Medicine Professor of Epidemiology Johns Hopkins Bloomberg School of Public Health Associate Director Johns Hopkins AIDS Service Director Garey Lambert Research Center

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ne of the issues in the Department of Health and Human Services (DHHS) guidelines still being explored and researched is the decision on when to start therapy. In years past, the prevailing thought was that delaying therapy until CD4+ counts reached a certain benchmark could benefit patients by allowing them to avoid side effects while also protecting them from developing resistance issues later during treatment. However, there has been a shift in thinking regarding the deferral of therapy. Emerging data have shown that there appears to be survival benefits when patients are started on HIV medications early. According to the DHHS guidelines, patients should receive treatment any time their CD4+ counts are below 350 cell/mm3. Now, clinicians have more evidence suggesting that treating patients when their CD4+ counts are higher than this threshold can also impact mortality.

Take the Best Shot First Experts in infectious disease have long believed that the first drug regimen selected to treat HIV is often the most successful. By developing an appropriate initial treatment plan, the risk for cross resistance can be minimized.

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Second- and third-line drug regimens are also showing efficacy as the medications for HIV have improved substantially in the past several years. However, it’s important to individualize initial treatments because selecting the right first regimen may enable patients to switch regimens less frequently, thus avoiding side effects and resistance issues that often accompany such switches.

Considerations When Initiating Treatment Several factors should be considered when selecting initial treatment regimens. For example, clinicians need to consider whether or not female patients plan to get pregnant or if they will be using contraception. Side effect profiles are also important because they can affect adherence. If adherence to specific drug regimens is questionable, it may behoove clinicians to select treatment plans associated with lower adherence risks, especially those involving lower pill burdens.

Some benefits of reduced pill burdens in HIV emerged from data in the CASTLE study. In this investigation, researchers demonstrated that once-daily protease inhibitor (PI) regimens for HIV were as effective as PI regimens that were taken twice daily. A side note to the CASTLE data is that adherence may improve since the pill burden is less. This information can be especially helpful when selecting initial PI regimens.

How to Motivate Patients When selecting initial treatment plans, clinicians should pay attention to patients’ willingness and capability to take regimens being prescribed to them as these issues can lead to poor adherence. Stacking the deck against HIV will only be beneficial if patients are motivated to take their medications as directed. The DHHS guidelines note that informing patients about the ramifications of poor adherence—including increased mortality from heart disease and other comorbidities, for example—can help further motivate patients to adhere to their regimens.

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Patients shouldn’t simply take their medications just to please their clinicians. They need to be informed about why they’re being put on specific drug regimens and understand their risks for resistance if they fail to take their HIV drug regimens as prescribed.

Clinicians can reinforce motivational strategies by addressing these issues proactively. Furthermore, clinicians should elicit adherence issues from patients and design regimens that promote adherence. Ask openended questions and avoid being judgmental. It’s not enough to know what percentage of doses patients take; clinicians also need to know their patterns of taking medications.

Financial Disclosure Statement Joel E. Gallant, MD, MPH, has indicated to Physician’s Weekly that he has received research support from Gilead, GlaxoSmithKline, Merck, Pfizer, Roche, and Tibotec. He has served on advisory boards for Bristol-Myers Squibb, Gilead, Merck, Panacos, Pfizer, Schering-Plough, and Tibotec, and has been a consultant for Abbott, GlaxoSmithKline, and Vertex. He has served on the data and safety monitoring board for Abbott, Gilead Sciences, and Koronis, and has received honoraria from Abbott, Gilead, GlaxoSmithKline, Monogram Biosciences, and Tibotec.

Readings and Resources Panel on Antiretroviral Guidelines for Adults and Adolescents.

Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.

November 3, 2008; 1-139. Available at www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed March 18, 2009.

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Considering Gender Differences in HIV Kathleen E. Squires, MD Professor of Medicine Jefferson Medical College of Thomas Jefferson University Director, Division of Infectious Diseases and Environmental Medicine Thomas Jefferson University Hospital

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IV has long been considered a disease restricted to homosexual men and injection drug users, but research has shown that heterosexual women account for more than 25% of all new HIV and AIDS diagnoses in the United States. This figure represents a significant increase from the 7% new diagnosis rate observed in 1985. Although homosexual activity is still a major reason for transmission of the infection, the most common way women contract the infection is through heterosexual activity. HIV is now appearing in women of all ages, but most often among those of reproductive age. Despite these climbing rates among women, many doctors still talk about HIV as if it’s a male disease.

Wanted: Open Dialogue Misconceptions among physicians and providers regarding gender and HIV are a significant concern.

For example, infected women—particularly those in monogamous relationships—may not be tested promptly, which can delay an HIV diagnosis. Even when women present with symptoms of HIV, physicians often won’t think to administer an HIV test, and women won’t ask for one. For physicians, it’s important to move away from the notion that HIV only affects certain kinds of women. The bottom

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line is that if a woman is sexually active, she should be considered for HIV testing. The communication lines need to open so that the social stigma associated with the infection can be overcome.

The CDC now recommends that all pregnant women—regardless of risk-factor status—be offered HIV testing. If other common risk factors are present, then more frequent testing may be required. Although women who are newly diagnosed with HIV are not typically planning to get pregnant in the near future, providers must remember that these feelings can change over time.

The risk of transmitting HIV from mother to baby can reach less than 1% with aggressive treatment and good prenatal care. By bringing up the topic of pregnancy early and revisiting it throughout treatment, physicians can help ensure that their patients will make the necessary changes to minimize their chances of passing the infection to their fetus. When assessing women with HIV who are of childbearing age, there should be a full discussion about the management of their reproductive potential, their hopes and aspirations, and whether or not they need to be on medication. If and when treatment is initiated, it’s important to follow current guidelines and consider drug-drug interactions between antiretroviral therapy and other medications—including oral contraceptives—when selecting treatment regimens.

Think About Side Effects Many people with HIV don’t start medication as soon as the diagnosis is made because there are risks and benefits for existing therapies. However, women planning to get pregnant in the near future can consider starting therapy early to help control viral replication. The goal is to get the viral load as low as possible to decrease the risk of HIV transmission to the fetus. All drug options and associated side effects should be discussed with women so that they make informed choices. Women need to

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be told about HIV medications that can lower the effectiveness of oral contraceptives. They also should understand that the risk of lipo­dystrophy and lactic acidosis is higher in women taking some antiretro­viral regimens. The key is to recognize warning signs of these potential complications and to discuss them so that patients know what to expect.

Financial Disclosure Statement Kathleen E. Squires, MD, has indicated to Physician’s Weekly that she has received grant/research support from Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Koronis, Merck, Schering-Plough, and Tibotec. She has also been on the scientific advisory board for Abbott, Boehringer-Ingelheim, BristolMyers Squibb, Gilead Sciences, GlaxoSmithKline, Koronis, Merck, Pfizer, Schering-Plough, Tibotec, and Tobira, and has been a consultant at Merck.

Readings and Resources Squires KE. Gender differences in the diagnosis and treatment of HIV. Gend Med. 2007;4:294-307.

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