Infectious Disease Advisor: Are there known differences in HIV infection between women and men?

Dr Gianella: Economic and sex/gender inequalities that promote unsafe sex and limit access to health services and education for women and girls continue to drive the HIV/AIDS epidemic in many countries.2 But there are also different biological factors between men and women that likely affect HIV disease.

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The most obvious differences are genetic (women and men have different chromosomes) and hormonal (as sex hormones — estrogen and progesterone in particular — affect how the immune system reacts to viral infections). This is not only true for HIV; overall, women have a different immune response compared with men. As a consequence, sex differences exist in biomarkers for HIV infection and disease progression.

Infectious Disease Advisor: What are the differences in HIV viral load and CD4 counts between women and men?

Dr Gianella: Generally both HIV-infected and uninfected women have more CD4 T cells compared with men.4 Women usually have lower viral loads during both acute and chronic infection compared with men.5-7 Women may be more likely to control HIV replication without therapy (so-called “HIV controller”) than men,2 but this is an area that requires more investigation. This seems to be a consequence of a stronger immune response in women, in which the virus can be controlled better during the earliest phase of infection. However, over the long run, this is exhausting the immune system and might be one reason why women — even if they have favorable prognostic factors — have similar (or even slightly accelerated) rates of progression to AIDS as men.  Women also seem to experience more complications such as more neurocognitive disease than men.8

Infectious Disease Advisor: Do women react differently to antiretroviral treatment (ART) compared with men?

Maile Young Karris, MD: Regardless of sex, if you take ART appropriately, you will respond. In most clinical trials, the efficacy of ART in women appears similar to men. However, women continue to be underrepresented in clinical studies of ART, which limits our ability to truly tease out if significant differences in terms of ART efficacy do exist.9

In fact, the pharmacokinetics and pharmacodynamics differ between men and women.  In studies that have looked at this, women usually have a higher level of drug exposure, which may partly explain why women tend to report more side effects from HIV therapies.10,11

Conversely, in the setting of HIV prevention, several clinical trials observed significantly lower efficacy of pre-exposure prophylaxis (PrEP) in women compared with men.12-16 In fact, data suggest that women need to take PrEP (currently only tenofovir disoproxil fumarate/emtricitabine is approved) consistently for 6 of 7 days to reach similar genital concentrations compared with men who take PrEP for 4 of 7 days.17,18 Biological factors that might play a role in reducing PrEP efficacy and penetration are currently under investigation.

Infectious Disease Advisor: You mention that women experience more adverse effects than men. Could you elaborate further?

Dr Karris: Studies do suggest that is the case, although we do not yet have sufficient data regarding newer drugs, such as the integrase strand transfer inhibitors. Multiple physiologic and genetic factors can contribute to this, including differences in weight, fat distribution, and liver enzyme activity (cytochrome P450).19