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Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

Melekhin VV, Shepherd BE, Stinnette SE, Rebeiro PF, Barkanic G, Raffanti SP, Sterling TR - PLoS ONE (2009)

Bottom Line: Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era.Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors.There were no statistical differences in rates of HIV disease progression between groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. vlada.melekhin@vanderbilt.edu

ABSTRACT

Background: Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.

Methods: We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).

Results: Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10) copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3), P = 0.03, respectively) but similar to those initiating HAART before pregnancy (-0.32 log(10) copies/mL, P = 0.96 and 155.8 cells/mm(3), P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups.

Conclusions: HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

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Estimated rate of HIV-1 RNA and CD4+ lymphocyte change.The estimated rate of HIV-1 RNA decline and CD4+ lymphocyte increase (small circles) and 95% confidence interval (vertical bars) by pregnancy group over the 6 months following HAART initiation, adjusted for baseline CD4+ lymphocyte count and HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, prior ADE, prior use of non-HAART ART, HAART type, prior pregnancies, and date of HAART start. Horizontal lines represent p-values in a pair-wise comparison (women who started HAART during pregnancy as a reference). Left panel: The estimated rate of HIV-1 RNA decline: −0.32 log10 copies/mL (95% CI −1.45, 0.81) in women who started HAART before pregnancy, −0.35 log10 copies/mL (95% CI −0.57, −0.13) in women who started HAART during pregnancy, and 0.10 log10 copies/mL (95% CI −0.46, 0.66) in women who started HAART after pregnancy. Right panel: The estimated rate of CD4+ lymphocyte increase: estimates were 155.8 cells/mm3 (95% CI −107.6, 419.2) in women who started HAART before pregnancy, 183.8 cells/mm3 (95% CI 110.8, 256.9) in women who started HAART during pregnancy, and −70.8 cells/mm3 (95% CI −326.8, 185.3) in women who started HAART after pregnancy.
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pone-0006961-g003: Estimated rate of HIV-1 RNA and CD4+ lymphocyte change.The estimated rate of HIV-1 RNA decline and CD4+ lymphocyte increase (small circles) and 95% confidence interval (vertical bars) by pregnancy group over the 6 months following HAART initiation, adjusted for baseline CD4+ lymphocyte count and HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, prior ADE, prior use of non-HAART ART, HAART type, prior pregnancies, and date of HAART start. Horizontal lines represent p-values in a pair-wise comparison (women who started HAART during pregnancy as a reference). Left panel: The estimated rate of HIV-1 RNA decline: −0.32 log10 copies/mL (95% CI −1.45, 0.81) in women who started HAART before pregnancy, −0.35 log10 copies/mL (95% CI −0.57, −0.13) in women who started HAART during pregnancy, and 0.10 log10 copies/mL (95% CI −0.46, 0.66) in women who started HAART after pregnancy. Right panel: The estimated rate of CD4+ lymphocyte increase: estimates were 155.8 cells/mm3 (95% CI −107.6, 419.2) in women who started HAART before pregnancy, 183.8 cells/mm3 (95% CI 110.8, 256.9) in women who started HAART during pregnancy, and −70.8 cells/mm3 (95% CI −326.8, 185.3) in women who started HAART after pregnancy.

Mentions: Figure 2 shows the unadjusted rate of HIV-1 RNA decline during the study period for all women in each of the three groups. After adjusting for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start, estimated HIV-1 RNA decline (95% confidence interval (CI)) over the 6 months after HAART initiation for those initiating during pregnancy was similar to that of women initiating prior to pregnancy (P = 0.96) but greater than that of women initiating after pregnancy (P = 0.03): −0.32 log10 copies/mL (95% CI−1.45, 0.81), −0.35 log10 copies/mL (95% CI −0.57, −0.13), and 0.10 log10 copies/mL (95% CI −0.46, 0.66) for women initiating HAART before, during, or after pregnancy, respectively (Figure 3 and Table 2).


Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

Melekhin VV, Shepherd BE, Stinnette SE, Rebeiro PF, Barkanic G, Raffanti SP, Sterling TR - PLoS ONE (2009)

Estimated rate of HIV-1 RNA and CD4+ lymphocyte change.The estimated rate of HIV-1 RNA decline and CD4+ lymphocyte increase (small circles) and 95% confidence interval (vertical bars) by pregnancy group over the 6 months following HAART initiation, adjusted for baseline CD4+ lymphocyte count and HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, prior ADE, prior use of non-HAART ART, HAART type, prior pregnancies, and date of HAART start. Horizontal lines represent p-values in a pair-wise comparison (women who started HAART during pregnancy as a reference). Left panel: The estimated rate of HIV-1 RNA decline: −0.32 log10 copies/mL (95% CI −1.45, 0.81) in women who started HAART before pregnancy, −0.35 log10 copies/mL (95% CI −0.57, −0.13) in women who started HAART during pregnancy, and 0.10 log10 copies/mL (95% CI −0.46, 0.66) in women who started HAART after pregnancy. Right panel: The estimated rate of CD4+ lymphocyte increase: estimates were 155.8 cells/mm3 (95% CI −107.6, 419.2) in women who started HAART before pregnancy, 183.8 cells/mm3 (95% CI 110.8, 256.9) in women who started HAART during pregnancy, and −70.8 cells/mm3 (95% CI −326.8, 185.3) in women who started HAART after pregnancy.
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pone-0006961-g003: Estimated rate of HIV-1 RNA and CD4+ lymphocyte change.The estimated rate of HIV-1 RNA decline and CD4+ lymphocyte increase (small circles) and 95% confidence interval (vertical bars) by pregnancy group over the 6 months following HAART initiation, adjusted for baseline CD4+ lymphocyte count and HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, prior ADE, prior use of non-HAART ART, HAART type, prior pregnancies, and date of HAART start. Horizontal lines represent p-values in a pair-wise comparison (women who started HAART during pregnancy as a reference). Left panel: The estimated rate of HIV-1 RNA decline: −0.32 log10 copies/mL (95% CI −1.45, 0.81) in women who started HAART before pregnancy, −0.35 log10 copies/mL (95% CI −0.57, −0.13) in women who started HAART during pregnancy, and 0.10 log10 copies/mL (95% CI −0.46, 0.66) in women who started HAART after pregnancy. Right panel: The estimated rate of CD4+ lymphocyte increase: estimates were 155.8 cells/mm3 (95% CI −107.6, 419.2) in women who started HAART before pregnancy, 183.8 cells/mm3 (95% CI 110.8, 256.9) in women who started HAART during pregnancy, and −70.8 cells/mm3 (95% CI −326.8, 185.3) in women who started HAART after pregnancy.
Mentions: Figure 2 shows the unadjusted rate of HIV-1 RNA decline during the study period for all women in each of the three groups. After adjusting for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start, estimated HIV-1 RNA decline (95% confidence interval (CI)) over the 6 months after HAART initiation for those initiating during pregnancy was similar to that of women initiating prior to pregnancy (P = 0.96) but greater than that of women initiating after pregnancy (P = 0.03): −0.32 log10 copies/mL (95% CI−1.45, 0.81), −0.35 log10 copies/mL (95% CI −0.57, −0.13), and 0.10 log10 copies/mL (95% CI −0.46, 0.66) for women initiating HAART before, during, or after pregnancy, respectively (Figure 3 and Table 2).

Bottom Line: Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era.Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors.There were no statistical differences in rates of HIV disease progression between groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. vlada.melekhin@vanderbilt.edu

ABSTRACT

Background: Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.

Methods: We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).

Results: Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10) copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3), P = 0.03, respectively) but similar to those initiating HAART before pregnancy (-0.32 log(10) copies/mL, P = 0.96 and 155.8 cells/mm(3), P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups.

Conclusions: HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

Show MeSH
Related in: MedlinePlus