Incidence and correlates of HIV-1 RNA detection in the breast milk of women receiving HAART for the prevention of HIV-1 transmission.
ABSTRACT: The incidence and correlates of breast milk HIV-1 RNA detection were determined in intensively sampled women receiving highly active antiretroviral therapy (HAART) for the prevention of mother-to-child HIV-1 transmission.Women initiated HAART at 34 weeks of pregnancy. Breast milk was collected every 2-5 days during 1 month postpartum for measurements of cell-associated HIV DNA and cell-free HIV RNA. Plasma and breast milk were also collected at 2 weeks, 1, 3 and 6 months for concurrent HIV-1 RNA and DNA measurements. Regression was used to identify cofactors for breast milk HIV-1 RNA detection.Of 259 breast milk specimens from 25 women receiving HAART, 34 had detectable HIV-1 RNA (13%, incidence 1.4 episodes/100 person-days 95% CI?=?0.97-1.9). Fourteen of 25 (56%) women had detectable breast milk HIV-1 RNA [mean 2.5 log(10) copies/ml (range 2.0-3.9)] at least once. HIV-1 DNA was consistently detected in breast milk cells despite HAART, and increased slowly over time, at a rate of approximately 1 copy/10(6) cells per day (p?=?0.02). Baseline CD4, plasma viral load, HAART duration, and frequency of breast problems were similar in women with and without detectable breast milk HIV-1 RNA. Women with detectable breast milk HIV-1 RNA were more likely to be primiparous than women without (36% vs 0%, p?=?0.05). Plasma HIV-1 RNA detection (OR?=?9.0, 95%CI?=?1.8-44) and plasma HIV-1 RNA levels (OR?=?12, 95% CI?=?2.5-56) were strongly associated with concurrent detection of breast milk HIV-1 RNA. However, no association was found between breast milk HIV-1 DNA level and concurrent breast milk HIV-1 RNA detection (OR?=?0.96, 95%CI?=?0.54-1.7).The majority of women on HAART had episodic detection of breast milk HIV-1 RNA. Breast milk HIV-1 RNA detection was associated with systemic viral burden rather than breast milk HIV-1 DNA.
Project description:Selenium supplementation for women infected with HIV may increase genital shedding of HIV-1, however, to our knowledge, no studies have examined the effect on viral shedding in breast milk. The aim of this study was to determine the effect of selenium supplementation on HIV-1 RNA detection in breast milk of HIV-infected women.HIV-infected pregnant women enrolled at 12 to 27 wk gestation in a randomized, double-blind, placebo-controlled trial of daily selenium (200 ?g as selenomethionine) had cell-free HIV-1 RNA quantified in breast milk at 4 to 9 wk postpartum. All participants received high-dose multivitamins containing vitamin B complex, C, and E as standard of care.The proportion of women with detectable (>50 copies/mL) HIV-1 RNA in breast milk appeared to be increased in the selenium group (36.4%) compared with those in the placebo group (27.5%) among the total cohort (N = 420), but results were borderline statistically significant (relative risk [RR], 1.32; 95% confidence interval [CI], 1.00-1.76; P = 0.05). In secondary analyses, the proportion of women with detectable HIV-1 RNA in breast milk was significantly greater in the selenium group (37.8%) compared with placebo group (27.5%) among women who did not receive highly active antiretroviral therapy (HAART; RR, 1.37; 95% CI, 1.03-1.82; P = 0.03). This relationship was primarily due to a significant effect of selenium among primiparous women (RR, 2.24; 95% CI, 1.30-3.86; P < 0.01), but not multiparous women (RR, 1.14; 95% CI, 0.81-1.59; P = 0.54) (P-value for interaction = 0.02). Too few women received HAART in this study (n = 12) to establish the effect of selenium supplementation.Selenium supplementation appears to increase HIV-1 RNA detection in breast milk among primiparous women not receiving HAART. Safety studies among pregnant women on HAART need to be conducted before administering selenium-containing supplements.
Project description:Defining the effect of antiretroviral regimens on breast milk HIV type-1 (HIV-1) levels is useful to inform the rational design of strategies to decrease perinatal HIV-1 transmission.Pregnant HIV-1 seropositive women (CD4+ T-cell count >250 and <500 cells/mm3) electing to breastfeed in Nairobi, Kenya were randomized to highly active antiretroviral therapy (HAART; zidovudine [ZDV], lamivudine and nevirapine [NVP]) during pregnancy and 6 months post-partum or to short-course ZDV plus single-dose NVP (ZDV/NVP). Breast milk samples were collected two to three times per week in the first month post-partum.Between November 2003 and April 2006, 444 breast milk samples were collected from 58 randomized women during the first month after delivery. Between 3 and 14 days post-partum, women in the HAART and ZDV/NVP arms had a similar prevalence of undetectable breast milk HIV-1 RNA. From 15 to 28 days post-partum, women in the HAART arm had significantly lower levels of breast milk HIV-1 RNA than women randomized to ZDV/NVP (1.7 log10 copies/ml [limit of detection] versus >2.10 log10 copies/ml, P<0.001). In contrast to breast milk HIV-1 RNA, suppression of plasma HIV-1 RNA during the neonatal period was consistently several log10 greater in the HAART arm compared with the ZDV/NVP arm.HAART resulted in lower breast milk HIV-1 RNA than ZDV/NVP; however, ZDV/NVP yielded comparable breast milk HIV-1 RNA levels in the first 2 weeks post-partum. Breast milk HIV-1 RNA remained suppressed in the ZDV/NVP arm despite increased plasma HIV-1 levels, which might reflect local drug effects or compartmentalization.
Project description:To evaluate the impact of highly active antiretroviral therapy (HAART) on CMV transmission and breast milk level in the context of maternal HIV. Specimens from a randomized trial conducted in Nairobi, Kenya between 2003-2005 were used to compare CMV transmission and breast milk levels between mother-infant pairs randomized to HAART versus short-course antenatal zidovudine plus single-dose nevirapine (ZDV/sdNVP) for prevention of mother-to-child HIV transmission (PMTCT). Fifty-one antiretroviral-naïve women ?32 weeks gestation, and CD4 between 200-500 cells/mm3 were randomized at 34 weeks to begin either antenatal ZDV/sdNVP, or HAART through 6 months postpartum. Mean breast milk CMV levels and transmission were compared between arms. Age, sociodemographics, CD4%, and HIV plasma RNA viral load were similar between arms at baseline. CMV viral loads were measured from 243 infant plasma and 185 breast milk specimens during the first year postpartum. The probability of infant CMV infection at 12 months was 19% lower in the HAART arm compared to ZDV/sdNVP (75% vs. 94%, p?=?.04). All women had CMV detected in breast milk, with 72%, 98%, and 97% testing positive during the first, second, and third weeks postpartum, respectively. There was a trend for early higher mean breast milk CMV level in the HAART arm at 1 week (p?=?.08), and there was significantly slower decline in breast milk CMV levels (area under the curve, p?=?.01). HAART started during the third trimester may decrease infant CMV infections, by mechanisms independent of breast milk CMV levels.NCT00167674.
Project description:<h4>Introduction</h4>Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis.<h4>Objective</h4>To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine).<h4>Methods</h4>Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant.<h4>Results</h4>HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median (interquartile range, IQR) of 1.5 ?g/mL (0.75-2.20 ?g/mL) and 1.04 ?g/mL (0.39-1.71 ?g/mL), respectively (P < 0.001). At 1 week postpartum, 93% and 98% of the women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 ?g/mL (0.13-0.39 ?g/mL) and 0.22 ?g/mL (0.13-0.34 ?g/mL), respectively. Maternal plasma and breast milk HIV-1 RNA correlated at all visits (R = 0.48, R = 0.7, R = 0.59; all P = 0.01). Subclinical mastitis was detected in 67% of the women at some time during 6 weeks, and in 38% of the breast milk samples. Breast milk samples with subclinical mastitis had significantly higher HIV-1 RNA at 1, 4 and 6 weeks (all P < 0.05).<h4>Conclusion</h4>After short-course antiretroviral prophylaxis, nevirapine was detectable in most infant cord blood samples and the concentration in maternal plasma and breast milk was high through week 1 accompanied by suppressed HIV-1 RNA in plasma and breast milk.
Project description:Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition.Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (? = 0.47; P = .005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P = .003) and maternal CD4 < 450 cells/mm(3) (HR, 1.8; P = .008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm(3) to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm(3).Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.
Project description:The risk of postnatal HIV transmission exists throughout the breastfeeding period. HIV shedding in breast milk beyond six months has not been studied extensively. The aim of this study was to determine prevalence and determinants of HIV shedding in breast milk during continued breastfeedingA cross-sectional study was nested in the PROMISE-PEP trial in Lusaka, Zambia to analyze breast milk samples collected from both breasts at week 38 post-partum (mid-way during continued breastfeeding). We measured concurrent HIV deoxyribonucleic acid (DNA) and HIV ribonucleic acid (RNA) as proxies for cell-associated HIV (CAV) and cell-free HIV (CFV) shedding in breast milk respectively. Participants' socio-demographic date, concurrent blood test results, sub clinical mastitis test results and contraceptive use data were available. Logistic regression models were used to identify determinants of HIV shedding in breast milk (detecting either CAV or CFV).The prevalence of HIV shedding in breast milk at 9 months post-partum was 79.4% (95%CI: 74.0 - 84.0). CAV only, CFV only and both CAV and CFV were detectable in 13.7%, 17.3% and 48.4% mothers, respectively. The odds of shedding HIV in breast milk decreased significantly with current use of combined oral contraceptives (AOR: 0.37; 95%CI: 0.17 - 0.83) and increased significantly with low CD4 count (AOR: 3.47; 95%CI: 1.23 - 9.80), unsuppressed plasma viral load (AOR: 6.27; 95%CI: 2.47 - 15.96) and severe sub-clinical mastitis (AOR: 12.56; 95%CI: 2.48 - 63.58).This study estimated that about 80% of HIV infected mothers not on ART shed HIV in breast milk during continued breastfeeding. Major factors driving this shedding were low CD4 count, unsuppressed plasma viral load and severe sub-clinical mastitis. The inverse relationship between breast milk HIV and use of combined oral contraceptives needs further clarification. Continued shedding of CAV may contribute to residual postnatal transmission of HIV in mothers on successful ART.
Project description:The effect of herpes simplex virus type 2 (HSV-2) suppression on human immunodeficiency virus type 1 (HIV-1) RNA in the context of prevention of mother-to-child transmission (PMTCT) interventions is unknown.Between April 2008 and August 2010, we conducted a randomized, double-blind trial of twice daily 500 mg valacyclovir or placebo beginning at 34 weeks gestation in 148 HIV-1/HSV-2 coinfected pregnant Kenyan women ineligible for highly active antiretroviral therapy (CD4 > 250 cells/mm(3)). Women received zidovudine and single dose nevirapine for PMTCT and were followed until 12 months postpartum.Mean baseline plasma HIV-1 RNA was 3.88 log(10) copies/mL. Mean plasma HIV-1 was lower during pregnancy (-.56 log(10) copies/mL; 95% confidence interval [CI], -.77 to -.34) and after 6 weeks postpartum (-.51 log(10) copies/mL; 95% CI, -.73 to -.30) in the valacyclovir arm than the placebo arm. Valacyclovir reduced breast milk HIV-1 RNA detection at 6 and 14 weeks postpartum compared with placebo (30% lower, P = .04; 46% lower, P = .01, respectively), but not after 14 weeks. Cervical HIV-1 RNA detection was similar between arms (P = .91).Valacyclovir significantly decreased early breast milk and plasma HIV-1 RNA among women receiving PMTCT.NCT00530777.
Project description:<h4>Background</h4>We evaluated the shedding of human immunodeficiency virus (HIV)-1 particles into continuous ambulatory peritoneal dialysis (CAPD) effluents of HIV-positive patients with end-stage renal disease (ESRD).<h4>Methods</h4>A total of 58 HIV-positive patients with ESRD on highly active antiretroviral therapy (HAART) who had Tenckhoff catheters inserted between September 2012 and February 2015 were prospectively reviewed and followed for 18 months. Peritoneal dialysis (PD) effluent samples from functioning CAPD catheters and plasma samples were obtained at three points during regular clinic visits on days 45?±?37, 200?±?19 and 377?±?13 after catheter insertion. All specimens were stored at?-20°C, and each batch was analysed by Roche quantitative HIV-1 polymerase chain reaction assay to detect HIV-1 particles. Clustered logistic regression was used to test for independent predictors of HIV-1 detection in CAPD effluents.<h4>Results</h4>HIV-1 RNA above 20 copies/mL assay limit was detectable in 19% (first batch), 26.3% (second batch) and 20% (third batch) of PD effluent specimens. HIV-1 RNA was detectable in PD fluid, without corresponding detection in the paired plasma in 3.4% (first batch), 5.3% (second batch) and 10% (third batch) of samples. Detection of HIV-1 in plasma sample (odds ratios 3.94; 95% confidence interval 1.14-13.55; P?=?0.030), body mass index, serum albumin and HAART regimen were found to be significantly associated with HIV-1 detection in PD effluents.<h4>Conclusions</h4>HIV particles are shed in detectable amounts into CAPD effluents even in patients with suppressed plasma viral load, raising concerns of a localized sanctuary site and potential infectivity of HIV-positive CAPD patients on a full complement of HAART.
Project description:The primary strategy to avoid mother-to-child transmission of human immunodeficiency virus (HIV) through breastfeeding is administration of highly active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur during pregnancy, quantifying HAART and the viral load in breast milk in this population is essential. Here, we developed an analytical assay for the simultaneous quantification of four ARV drugs in breast milk using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We validated this method following Mexican and international guidelines. ARV drugs. We extracted the ARV drugs from 200 ?L samples of breast milk and detected these drugs in a triple quadrupole mass spectrometer with positive electrospray ionization. The validated concentration ranges (ng/mL) for zidovudine, lamivudine, lopinavir, and ritonavir were 12.5-750, 50-2500, 100-5000 and 5 to 250, respectively. Additionally, the absolute recovery percentages (and matrix effects) were 91.4 (8.39), 88.78 (28.75), 91.38 (11.77) and 89.78 (12.37), respectively. We determined that ARV drugs are stable for 24 h at 8°C and 24°C for 15 days at -80°C. This methodology had the capacity for simultaneous detection; separation; and accurate, precise quantification of ARV drugs in human breast milk samples according to Mexican standard laws and United States Food and Drug Administration guidelines.
Project description:Single-dose nevirapine (NVP) (sdNVP) can reduce the risk of HIV vertical transmission. We assessed risk factors for NVP resistance in plasma and breast milk from sdNVP-exposed Ugandan women.Samples were analyzed using the Roche AMPLICOR HIV-1 Monitor Test Kit, version 1.5, and the ViroSeq HIV-1 Genotyping System. NVP concentrations were determined by liquid chromatography with tandem mass spectroscopy.HIV genotypes (plasma and breast milk) were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, two recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples. There was a nonsignificant trend between detection of NVP resistance in breast milk and plasma (P = 0.06). There was no association of HIV resistance in breast milk with median maternal pre-NVP viral load or CD4 cell count, median breast milk viral load at 4 weeks, breast milk sodium more than 10 mmol/l, HIV subtype, or concentration of NVP in breast milk or plasma.NVP resistance was frequently detected in breast milk 4 weeks after sdNVP exposure. In this study, we were unable to identify specific factors associated with breast milk NVP resistance.