The use of combination antiretroviral therapy during pregnancy has enabled us to decrease perinatal HIV transmission to less than 1%, in areas with adequate resources. Questions remain regarding the safety of these medications for the mother, fetus, and child. Recent publications present conflicting data about associations between antiretrovirals and prematurity and other adverse pregnancy outcomes, and if highly active antiretroviral therapy (HAART) is necessary for all pregnant women. The pharmacokinetics of some antiretroviral medications are altered significantly during pregnancy; placental transfer to the fetus is variable. The well-documented benefit of HAART for preventing mother-to-child transmission generally outweighs the potential risks to the fetus, infant, and mother. However, potential adverse effects are of concern, and questions remain as to the optimal treatment strategy. More data on the effects of antiretrovirals during pregnancy are needed.
"It is plausible that pregnancy may influence the timing of HAART initiation and therapeutic outcomes in HIV. Pregnancy may affect pharmacokinetics that could influence side effects.18–20 Pregnancy may contribute to greater drug intolerance in female recipients and higher rates of treatment discontinuation as following delivery HAART may be stopped depending on patient and physician preferences towards remaining on treatment (dependent on disease stage). "
[Show abstract][Hide abstract] ABSTRACT: The influence of biological sex on human immunodeficiency virus (HIV) antiretroviral treatment outcome is not well described in HIV-hepatitis C (HCV) coinfection.
We assessed patients' clinical outcomes of HIV-HCV coinfected patients initiating antiretroviral therapy attending the Ottawa Hospital Immunodeficiency Clinic from January 1996 to June 2008.
We assessed 144 males and 39 females. Although similar in most baseline characteristics, the CD4 count was higher in females (375 vs 290 cells/muL). Fewer females initiated ritonavir-boosted regimens. The median duration on therapy before interruption or change was longer in males (10 versus 4 months) (odds ratio [OR] 1.40 95% confidence interval: 0.95-2.04; P = 0.09). HIV RNA suppression was frequent (74%) and mean CD4 count achieved robust (over 400 cells/muL) at 6 months, irrespective of sex. The primary reasons for therapy interruption in females and males included: gastrointestinal intolerance (25% vs 19%; P = 0.42); poor adherence (22% vs 15%; P = 0.31); neuropsychiatric symptoms (19% vs 5%; P = 0.003); and lost to follow-up (3% vs 13%; P = 0.08). Seven males (5%) and no females discontinued therapy for liver-specific complications. Death rate was higher in females (23% vs 7%; P = 0.003).
There are subtle differences in the characteristics of female and male HIV-HCV coinfected patients that influence HIV treatment decisions. The reasons for treatment interruption and change differ by biological sex. This knowledge should be considered when starting HIV therapy and in efforts to improve treatment outcomes.
Patient Preference and Adherence 05/2010; 4:97-103. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: WR1065 is the free-thiol metabolite of the cytoprotective aminothiol amifostine, which is used clinically at very high doses to protect patients against toxicity induced by radiation and chemotherapy. In an earlier study we briefly reported that the aminothiol WR1065 also inhibits HIV-1 replication in phytohemagglutinin (PHA)-stimulated human T-cell blasts (TCBs) infected in culture for 2 hr before WR1065 exposure. In this study we expanded the original observations to define the dose-response curve for that inhibition, and address the question of additive effects for the combination of WR1065 plus Zidovudine (AZT). Here we also explored the effect of WR1065 on SIV by examining TCBs taken from macaques with well-established infections several months with SIV.
TCBs from healthy human donors were infected for 2 hr with HIV-1, and viral replication (p24) was measured after 72 hr of incubation with or without WR1065, AZT, or both drugs. HIV-1 replication, in HIV-1-infected human TCBs, was inhibited by 50% at 13 microM WR1065, a dose at which 80% of the cells were viable. Cell cycle parameters were the same or equivalent at 0, 9.5 and 18.7 microM WR1065, showing no drug-related toxicity. Combination of AZT with WR1065 showed that AZT retained antiretroviral potency in the presence of WR1065. Cultured CD8+ T cell-depleted PHA-stimulated TCBs from Macaca mulatta monkeys chronically infected with SIV were incubated 17 days with WR1065, and viral replication (p27) and cell viability were determined. Complete inhibition (100%) of SIV replication (p27) was observed when TCBs from 3 monkeys were incubated for 17 days with 18.7 microM WR1065. A lower dose, 9.5 microM WR1065, completely inhibited SIV replication in 2 of the 3 monkeys, but cells from the third macaque, with the highest viral titer, only responded at the high WR1065 dose.
The study demonstrates that WR1065 and the parent drug amifostine, the FDA-approved drug Ethyol, have antiretroviral activity. WR1065 was active against both an acute infection of HIV-1 and a chronic infection of SIV. The data suggest that the non-toxic drug amifostine may be a useful antiretroviral agent given either alone or in combination with other drugs as adjuvant therapy.
AIDS Research and Therapy 11/2009; 6(1):24. DOI:10.1186/1742-6405-6-24 · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detectable HIV-1 RNA at delivery is the strongest predictor of mother-to-child transmission. The risk factors for detectable HIV, including type of regimen, are unknown. We evaluated factors, including highly active antiretroviral (HAART) regimen, associated with detectable HIV-1 RNA at delivery in the Women and Infants Transmission Study (WITS).
Data from 630 HIV-1-infected women who enrolled from 1998 to 2005 and received HAART during pregnancy were analyzed. Multivariable analyses examined associations between regimens, demographic factors, and detectable HIV-1 RNA (>400 copies/milliliter) at delivery.
Overall, 32% of the women in the cohort had detectable HIV-1 RNA at delivery. Among the subset of 364 HAART-experienced women, a lower CD4 cell count at enrollment [adjusted odds ratio (AOR) = 1.20 per 100 cells/microL, confidence interval (CI) 1.04 to 1.37] and higher HIV-1 RNA at enrollment (AOR = 1.52 per log10 copies/milliliter, CI 1.32 to 1.75) were significantly associated with detectable HIV-1 RNA levels at delivery. For the 266 HAART-naive women, both lower CD4 cell count at enrollment (AOR = 1.24 per 100 cells/microL, CI 1.05 to 1.48) and higher HIV-1 RNA at enrollment (AOR = 1.35 per log10 copies/milliliter, CI 1.12 to 1.63) were associated with detectable HIV-1 RNA at delivery. In addition, age at delivery (AOR = 0.92 per 10 years older, CI 0.86 to 0.99) and maternal illicit drug use (AOR = 3.15, CI 1.34 to 7.41) were significantly associated with detectable HIV-1 RNA at delivery among HAART-naive women. Type of HAART regimen was not significant in either group.
Lack of viral suppression at delivery was common in the WITS cohort, but differences by antiretroviral regimen were not identified. Despite a transmission rate below 1% in the last 5 years of the WITS cohort, improved measures to maximize HIV-1 RNA suppression at term among high-risk women are warranted.
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