Genital tract HIV RNA levels and their associations with human papillomavirus infection and risk of cervical precancer.

OBJECTIVE: Plasma HIV RNA levels have been associated with the risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia. DESIGN/METHODS: In an HIV-seropositive women's cohort with semiannual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions (HSIL) subclassified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incidents of severe HSIL were matched to 130 controls by age, CD4 count, highly active antiretroviral therapy use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects. RESULTS: Risk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable, 2.96; 95% confidence interval: 0.99 to 8.84; Ptrend = 0.03). However, this association became nonsignificant (Ptrend = 0.51) after adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend = 0.02) and persistence of oncogenic HPV (Ptrend = 0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels. CONCLUSIONS: These prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical precancer in HIV-seropositive women, but they leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumorigenesis.

Maternal antiretroviral use during pregnancy and infant congenital anomalies: the NISDI perinatal study.

BACKGROUND: We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. METHODS: The study population consisted of first singleton pregnancies on study, > or =20 weeks gestation, among women enrolled in NISDI from Argentina and Brazil who delivered between September 2002 and October 2007. CAs were defined as any major structural or chromosomal abnormality, or a cluster of 2 or more minor abnormalities, according to the conventions of the Antiretroviral Pregnancy Registry. CAs were identified from fetal ultrasound, study visit, and death reports. Prevalence rates [number of CAs per 100 live births (LBs)] were calculated for specific ARVs, classes of ARVs, and overall exposure to ARVs. RESULTS: Of 1229 women enrolled, 995 pregnancy outcomes (974 LBs) met the inclusion criteria. Of these, 60 infants (59 LBs and 1 stillbirth) had at least 1 CA. The overall prevalence of CAs (per 100 LBs) was 6.2 [95% confidence interval (CI) 4.6 to 7.7]. The prevalence of CAs after first trimester ARVs (6.2; 95% CI 3.1 to 9.3) was similar to that after second (6.8; 95% CI 4.5 to 9.0) or third trimester (4.3; 95% CI 1.5 to 7.2) exposure. The rate of CAs identified within 7 days of delivery was 2.36 (95% CI 1.4 to 3.3). CONCLUSIONS: The prevalence of CAs after first trimester exposure to ARVs was similar to that after second or third trimester exposure. Continued surveillance for CAs among children exposed to ARVs during gestation is needed.

Effect of antiretroviral therapy on the incidence of genital warts and vulvar neoplasia among women with the human immunodeficiency virus.

OBJECTIVE: The purpose of this study was to determine the incidence and predictors of genital warts and vulvar intraepithelial neoplasia among women with the human immunodeficiency virus. STUDY DESIGN: This was a multicenter prospective cohort study comprised of women without warts or vulvar intraepithelial neoplasia at baseline who underwent CD4 count, human immunodeficiency virus RNA measurement, examination, Papanicolaou test, and biopsy, as indicated, every 6 months. Human papillomavirus DNA typing was examined at baseline. RESULTS: The incidence of warts among women who were human immunodeficiency virus seronegative was 1.31 versus 5.01 per 100 person-years among women who were seropositive (P < .001). Incidence of vulvar intraepithelial neoplasia among women who were seronegative was 1.31 versus 4.67 per 100 person-years among women who were seropositive (P < .001). In multivariable analysis, warts were associated with highly active antiretroviral therapy (relative hazard, 0.76), CD4 count (relative hazard, 0.91/100 cell/cm(2) increase), acquired immunodeficiency syndrome (relative hazard, 1.25), abnormal Papanicolaou test results (relative hazard, 2.18), high- or medium-risk human papillomavirus types (relative hazard, 1.91), low-risk human papillomavirus types (relative hazard, 1.48), smoking (relative hazard, 1.43), having 1 child (relative hazard, 1.54), and age (relative hazard, 0.74/10 years). Vulvar intraepithelial neoplasia was linked to highly active antiretroviral therapy (relative hazard, 0.65), CD4 count (relative hazard, 0.92), abnormal Papanicolaou test results (relative hazard, 16.03), high- or medium-risk human papillomavirus types (relative hazard, 1.37), and age (relative hazard, 0.85/10 years). CONCLUSION: Warts and vulvar intraepithelial neoplasia are common among women with human immunodeficiency virus. Highly active antiretroviral therapy decreases their incidence.