The Role of Gender in HIV Progression

Ross G. Hewitt, MD; Nader Parsa, PhD; Lawrence Gugino, MD

Disclosures

AIDS Read. 2001;11(1) 

In This Article

HAART in Women

In Australia, women were shown to be significantly less likely than men to be receiving antiretroviral therapy, to be using prophylactic treatments, and to be optimistic about the benefits of therapy.[54] Women felt isolated from both community and medical responses to HIV infection. Women with dependent children were more likely to accept antiretroviral therapy.

While most studies would indicate that the efficacy of the various reverse transcriptase inhibitors and/or protease inhibitors (PIs) is equal among women and men,[55,56,57,58,59,60,61] some authors have observed lower rates of viral suppression. In New Orleans, women had an OR of 1.55 (95% CI, 1.07 to 2.25) of having a viral load greater than 400 copies/mL.[62] Women were also significantly more likely to have their HAART regimen changed and to experience depression during the study. In a study of 249 women receiving HAART, with baseline CD4 cell count of 182/µL and viral load of 64,317 copies/mL, only 34% achieved durable viral suppression.[63] These women did experience a significantly greater increase in CD4 cell count.

While women can respond to HAART, the toxicity may be different. In a retrospective review of HAART, women were found to have a statistically increased risk of adverse drug reactions compared with men (P = .008), with occurrence in 25% of men and 37% of women.[64] A study of adverse effects of the PI ritonavir in 90 women compared with 996 men showed that women were more likely to have nausea, vomiting, malaise, fatigue, and numbness and tingling around the mouth but were less likely to have diarrhea.[65] Women receiving the PI nelfinavir were more likely to have stomach pain, itching, and rash but less likely to have diarrhea.[66]

Women can also experience body habitus changes and serum lipid abnormalities while receiving HAART (a single PI with 2 nucleoside reverse transcriptase inhibitors).[67] Changes included increase in abdominal size and breast size, weight gain of greater than 5 kg (11 lb), peripheral fat wasting, buttock fat wasting, and development of cervicodorsal fat pad. HAART was also associated with significant increases in total cholesterol, apolipoprotein B, and high-density lipoprotein cholesterol levels. When compared with men, women had significantly more fat accumulation but not fat depletion or the combination of fat accumulation and depletion.[68]

Studies of adherence are gaining increased relevance, because it is apparent that HAART works only if the patient takes it, and medication-taking behavior is influenced by many factors. The association of adherence with viral load and CD4 T-lymphocyte counts was striking when adherence to a nelfinavir-based regimen was measured with electronic pill monitors.[69] Adherence clearly determined the outcome of treatment with HAART. In British Columbia, using prescription refills as the measure for adherence to HAART, men had a nearly 2-fold better rate of adherence than women.[70] Within a multicenter, prospective women's cohort, levels of self-reported adherence were quite high (74% of women reporting greater than 95% adherence), yet only 39% of these women achieved undetectable viral loads.[71] Significantly higher levels of crack cocaine use and depression were observed in women with poor and moderate self-reported adherence.

Anemia associated with hypermenorrhea developed in 4 of 10 women who began treatment with HAART at a clinic in Denmark.[72] All 4 were receiving ritonavir, and symptoms resolved in 3 of the women following substitution of a different PI. The women had normal menstrual function before therapy and did not experience intramenstrual bleeding.

Several antiretroviral agents are known to interfere with the metabolism of oral contraceptives. Nevirapine induces those enzymes that metabolize ethinyl estradiol, leading to a clinically relevant decrease in the area under the concentration-time curve (AUC) of oral contraceptives that contain this agent.[73] Similarly, the glucuronosyltransferase enzyme system is induced by ritonavir and nelfinavir, also leading to a 40% and 47% decrease, respectively, in the AUC of ethinyl estradiol in women taking oral contraceptives.[74,75] Indinavir is associated with a 24% increase in levels of ethinyl estradiol and a 26% increase in levels of norethindrone in patients taking oral contraceptives, but the changes are not felt to be clinically significant.[76]

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