CASE #1

Ms. J. is a 47-year-old Black woman who presents with fever, oral ulcers, pharyngitis, and cervical lymphadenopathy.Work-up to date is negative, though Ms. J. elected to opt out of HIV testing because she feels that she is not at risk. She states that she has never used illicit drugs of any sort and has had a monogamous sexual partner (though he never uses condoms). After further discussion, Ms. J. agrees to HIV testing and is found to have a positive rapid test and an indeterminate Western Blot.

COMMENT: Though Ms. J. presents with symptoms suggestive of acute retroviral syndrome, these symptoms are also consistent with a number of other diagnoses. In a prospective cohort study, Hecht et. al found that fever (Odds ratio 5.2; 95% CI 2.3-11.7) and rash (Odds ratio 4.8; 95% CI 2.4-9.8) were strongly associated, by multivariate analysis, with the presence of acute retroviral infection.¹ The Western Blot should be repeated in several weeks, and HIV RNA testing may be helpful in defining likely presence of HIV infection.

The CDC recently estimated that:

• 56,300 HIV new infections occur annually in the U.S., a more accurate estimate than previous approximations of 40,000 annual new U.S. infections.²
  
  
• Noteworthy is that 27% of U.S. infections now occur in women,³ an increase from 20 years ago. Black women are disproportionately affected, constituting 66% of US women with HIV infection in 2005, but only 13% of the US female population.^4,5
  
  
• Many women perceive themselves to be at “low risk” for HIV infection as does Ms. J. In a survey of obstetricians and gynecologists, Gray, et al. reported that the major reason women decline HIV testing is that they reportedly believe themselves to be at low risk for HIV acquisition.⁶
  
  
• Black women without high risk behaviors may be at increased risk for HIV acquisition compared with their white counterparts.
  
  
• Hallfors, et al., in a study population of 8,706 non-Latino blacks and whites 18-26 years of age, found that in a subgroup of individuals with low risk behaviors, both Black men and women were 25 times more likely than their white counterparts to acquire a sexually transmitted infection (STI) and/or HIV infection. These data suggest that the risk of STI and HIV infection is not only associated with their behaviors but also with the risk behaviors of their partners or other unmeasured factors.⁷
  

CASE #2

Ms. L. is a 33-year-old woman who comes to your office for routine HIV follow-up. She has been aware of her HIV infection for the past year and has been followed at another clinic. She advises you that she has never had any opportunistic infections; however, she has been told that she should consider starting antiretroviral therapy. Physical examination is normal, hermost recent CD4+ count is 320 cells/mm,³ and her HIV RNA viral load is 110,000 copies/ml. You and she decide that it is time to start antiretroviral therapy.

Which of the following do you choose?

1. Efavirenz + zidovudine/lamivudine as a fixed dose combination
   because current data suggest that efficacy is better than the alternatives.
2. Efavirenz/tenofovir/emtricitabine as a fixed dose combination
   because recent data indicate that time to virologic failure is longer with
   this combination compared with alternatives.
3. Lopinavir/ritonavir (fixed dose combination) + abacavir/lamivudine
   because the incidence of lipoatrophy is less than with efavirenz-based
   regimens.
4. Darunavir + ritonavir + tenofovir/emtricitabine because recent
   96-week trial data in antiretroviral naïve patients demonstrate superiority
   to lopinavir/ritonavir-based therapy.
5. Further discussion with the patient to determine her toxicity concerns
   regarding antiretroviral therapy as well as her reproductive needs.

Efavirenz (EFV), a component of regimens in answers A and B, is classified as an FDA Pregnancy Category Class D drug; animal data show an increased risk of central nervous system (CNS) defects and there have been several retrospective reports of CNS defects in infants exposed to efavirenz.¹⁰ As the neural tube forms in the first month of pregnancy, EFV should not be used in women of child-bearing potential unless a barrier form of contraception as well as another method of contraception (e.g., hormonal contraception) are consistently used. In addition, a negative pregnancy test result should always be documented before initiation of EFV. Tenofovir/emtricitabine combined with efavirenz has been demonstrated to have superior durability of virologic control as well as an improved safety profile compared with zidovudine/ lamivudine combined with efavirenz,¹¹ and less lipoatrophy has been reported with lopinavir/ritonavir-containing regimens when compared to efavirenz regimens.¹² Noteworthy, is that the November 3, 2008 Department of Health and Human Services (DHHS) Guidelines continue to recommend tenofovir with either lamivudine or emtricitabine as the preferred nucleoside reverse transcriptase inhibitor (NRTI) backbone.¹³

The combination of Abacavir + lamivudine was recently moved from preferred to alternative NRTI status in the DHHS guidelines for two reasons:
1) IN ACTG (AIDS Clinical Trials Group) 5202, a large randomized study in treatment naïve persons comparing tenofovir/emtricitabine to abacavir/lamivudine when used in combination with either efavirenz or with atazanavir/ritonavir, the Data Safety Monitoring Board (DSMB) recommended termination of the study in participants with starting viral loads ≥100,000 copies/ml, Case No. 2 as data demonstrated a shorter time to virologic failure if they had been randomized to abacavir/lamivudine (ABC/3TC) compared to individuals randomized to tenofovir/ emtricitabine (TDF/FTC).¹⁴ Participants with starting viral loads <100,000 copies/ml remain on study. It is noteworty that 96-week data from a smaller study (the HEAT Study) comparing ABC/3TC to TDF/FTC, each in combination with lopinavir/ritonavir, did not demonstrate significant differences in the proportion of virologically suppressed patients with starting viral loads ≥100,000 copies/ml among participants randomized to the two arms.¹⁵

2) TWO STUDIES have indicated an increased incidence of myocardial infarction among patients currently (or within six months) of taking abacavir.^16,17 Though a pooled analysis of clinical trials involving 9,639 patients taking abacavir (compared with 5,044 participants not taking abacavir) did not reveal an elevated risk of myocardial infarction,¹⁸ the guidelines committee concluded that ABC/3TC should be used with caution in patients with HIV RNA viral loads >100,000 copies/ml or with increased cardiovascular risk.¹³ Ritonavir boosted darunavir with tenofovir/emtricitabine has been shown to be superior to lopinavir/ ritonavir + tenofovir/emtricitabine.¹⁹ However, there are scant data on use of darunavir in pregnant women. It is noteworthy that ritonavir-boosted darunavir was designated as a “preferred” protease inhibitor in the most recent DHHS guidelines.¹³