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Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
Methods and Findings
The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo.
Citation: Tonwe-Gold B, Ekouevi DK, Viho I, Amani-Bosse C, Toure S, Coffie PA, et al. (2007) Antiretroviral Treatment and Prevention of Peripartum and Postnatal HIV Transmission in West Africa: Evaluation of a Two-Tiered Approach. PLoS Med 4(8): e257. https://doi.org/10.1371/journal.pmed.0040257
Academic Editor: Lynne Mofenson, National Institute of Child Health and Human Development, United States of America
Received: November 27, 2006; Accepted: July 11, 2007; Published: August 21, 2007
Copyright: © 2007 Tonwe-Gold et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The Abidjan MTCT-Plus care and treatment program is supported by the MTCT-Plus Initiative through the International Center for AIDS Care and Treatment Programs (ICAP) at the Columbia University Mailman School of Public Health, New York. The MTCT–Plus Initiative is funded by several private US foundations (http://www.mtctplus.org). The funders of the MTCT Plus Initiative did not have any direct role in the study design, data collection or analysis. The members of the MTCT Plus Initiative Secretariat have agreed on the decision to publish and have helped in the preparation of the manuscript. The ANRS 1201/1202 Ditrame Plus project on which the MTCT-Plus Abidjan programme was built, was funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (Paris, France), with additional support from the Charity Sidaction (Paris, France).
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: 3TC, lamivudine; ART, antiretroviral therapy; ARV, antiretroviral; CI, confidence interval; d4T, stavudine; HAART, highly active antiretroviral treatment; IQR, interquartile range; NVP, nevirapine; PMTCT, prevention of mother-to-child transmission of HIV; sc, short course; sd, single dose; WHO, World Health Organization; VL, viral load; ZDV, zidovudine
Editors' Summary
Effective treatments are available to prevent AIDS in people who are infected with HIV, but not everyone with HIV needs to take medication. Usually, anti-HIV medication is recommended only for those whose immune systems have been significantly affected by the virus, as evidenced by symptoms or by the results of a blood test, the CD4 lymphocyte ("T cell") count. Treating HIV usually requires a combination of three or more medications. These combinations (called HAART) must be taken every day, can cause complications, and can be expensive.
Worldwide, more than half a million children became infected with HIV each year. Most of these children acquire HIV from their mothers during pregnancy or around the time of birth. If a pregnant woman with HIV takes HAART, her chances of passing HIV to the baby are greatly reduced, but the possible side effects of HAART on the baby are not known. Also, most transmission of HIV from mothers to babies occurs in poor countries where supplies of HAART are limited. For these reasons, World Health Organization (WHO) does not recommend that every pregnant woman receive HAART to prevent HIV transmission to the baby, unless the woman needs HAART for her own health (for example if her T cells are low or she has severe symptoms of HIV infection). For pregnant women with HIV who do not need to take HAART for their own health, less complicated treatments, involving a short course of one or two HIV drugs, can be used to reduce the risk of passing HIV to the baby.
Why Was This Study Done?
The WHO recommendations for HAART in pregnancy are based on the best available evidence, but it is important to know how well they work in actual practice. The authors of this study were providing HIV treatment to pregnant women with HIV in West Africa through an established clinic program in Abidjan, Côte d'Ivoire, and wanted to see how well the WHO recommendations for HAART or short-course treatments, depending on the mother's condition, were working to protect babies from HIV infection.
What Did the Researchers Do and Find?
The researchers studied 250 HIV-infected pregnant women who received HIV medications in the Abidjan program between mid-2003 and mid-2005. In accordance with WHO guidelines, 107 women began HAART for their own health during pregnancy, and 143 women did not qualify for HAART but received other short course treatments (scARV) to prevent HIV transmission to their babies. The authors monitored mothers and babies for treatment side effects and tested the babies for HIV infection up to age 1 y.
They found that HAART was relatively safe during pregnancy, although babies born to women on HAART were more likely (26.3%) to have low birth weight than babies born to women who received scARV (12.4%). Also, 7.5% of women on HAART developed side effects requiring a change in their medications. Combining the results from HAART and scART groups, the chance of HIV transmission around the time of birth was 2.2%, increasing to 5.7% at age 1 y. (Three-quarters of the infants were breast-fed; safe water for mixing formula was not reliably available.) The study found no difference in risk of HIV infection between babies whose mothers received HAART and those whose mothers received scARV according to guidelines.
What Do These Findings Mean?
These results support the safety and effectiveness of the WHO two-tiered approach for preventing mother-to-child transmission. This study was not designed to compare HAART to scART directly, because the women who received HAART were the ones with more advanced HIV infection, which might have affected their babies in many ways.
Compared to earlier pregnancy studies of HAART in rich countries, this study of the WHO approach in West Africa showed similar success in protecting infants from HIV infection around the time of birth. Unfortunately, because formula feeding was not generally available in resource-limited settings, protection declined over the first year of life with breast-feeding, but some protection remained.
This study confirms that close monitoring of pregnant women on HAART is necessary, so that drugs can be changed if side effects develop. The study does not tell us whether using scARV in pregnancy might change the virus in ways that would make it more difficult to treat the same women with HAART later if they needed it. The reason for low birth weight in some babies born to mothers on HAART is unclear. It may be because the women who needed HAART had more severe health problems from their HIV, or it may be a result of the HAART itself.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040257.
- World Health Organization has a page on prevention of mother-to-child transmission of HIV
- "Women, Children, and HIV" is a resource site from the François Xavier Bagnoud Center and UCSF
- The MTCT-Plus initiative at Columbia University supports the programs in Abidjan
Mother-to-child transmission (MTCT) of HIV-1 is estimated to be the cause of at least 90% of paediatric HIV infections, with more than 700,000 children newly infected in 2006 worldwide [1]. New HIV infections in children are becoming increasingly rare in Western Europe (200 reported in 2004) and the United States (300) [1,2]. In these relatively resource-rich contexts, the availability of highly active antiretroviral therapy (HAART), usually three antiretroviral (ARV) drugs during pregnancy, in combination with the avoidance of breast-feeding and with elective caesarean section, has reduced the transmission rate to less than 2% and resulted in the near elimination of MTCT [1–3].
In sub-Saharan Africa, progress has been made in the last few years toward expanding prevention of MTCT (PMTCT) programs based on trial findings that have demonstrated the efficacy of generally simpler and shorter ARV prophylactic regimens than those used in industrialized countries [4–9]. This expansion has been based primarily on the use of single-dose nevirapine (sdNVP) and, to a lesser extent, short-course antiretroviral (scARV) regimens of one or two drugs administered at the end of pregnancy and followed with sdNVP to prevent peripartum transmission. Postnatal transmission of HIV, resulting in 9.8 new HIV infections per 100 child-years of breast-feeding overall, and occurring most frequently in women with low CD4 T cell counts [10], reduces the long-term overall efficacy of peripartum ARV regimens [11].
World Health Organization (WHO) had set a target of treating three million individuals in the developing world with HAART by 2005 [12], and the United Nations General Assembly Special Session on HIV/AIDS committed countries to reducing by 20% the proportion of infants infected with HIV by 2005 [13]. In this context, WHO guidelines for the prevention of perinatal transmission in low-resource settings now recommend using HAART for pregnant women in need of ARV therapy (ART) for their own health [14]. This policy was agreed upon in recognition of the potential impact of HAART on decreasing morbidity and mortality in women with advanced HIV disease, as well as its potentially profound effect on preventing peripartum and postnatal HIV infection. Currently, access to HAART for pregnant women in low-income countries is limited, and there are few documented experiences from African countries [15]. Although HAART is widely used for peripartum PMTCT in industrialized countries [2,3,16], its efficacy and safety have not been fully assessed in resource-limited settings characterised by high HIV seroprevalence, and few data are available to assess the impact of ART on postnatal transmission.
We evaluated a two-tiered PMTCT strategy in pregnant women enrolled at the MTCT-Plus Initiative care and treatment program in Abidjan, Côte d'Ivoire: on the basis of their medical status (CD4 T cell count and WHO stage) they were given either HAART or scARV for PMTCT. HAART was targeted at pregnant women with advanced HIV disease who met WHO eligibility criteria for treatment and scARV regimens for PMTCT were prescribed to women with less advanced HIV disease. We report the safety of HAART in pregnant women and the 4 wk and 12 mo outcomes for infant HIV infection and mortality for this stepped PMTCT strategy.
Study Design and Participants
This observational cohort included women enrolled in the MTCT-Plus Initiative, a multi-country, comprehensive HIV care and treatment program for pregnant and postpartum women and their families built on existing PMTCT services. It provides pregnant and postpartum women with holistic, family-centred HIV care including HAART to the woman, her partner, and her children [17]. Pregnant women identified as HIV-infected at two community-based antenatal clinics in two low-income urban districts of Abidjan were referred for enrolment into the MTCT-Plus program. The study population included all HIV-infected pregnant women and their live-born infants enrolled between August 2003 and April 2005 and followed until a final paediatric HIV status could be determined. Women were divided into two groups. The first cohort included the HIV-infected pregnant women who were eligible for HAART based on WHO criteria (at high risk of transmission); the second cohort included HIV-infected pregnant women who were not eligible for HAART and received sc-PMTCT (with low risk of transmission).
The MTCT-Plus program was reviewed by the institutional review board (IRB) from Columbia University in 2000 (principal sponsor) and was not considered a research project but rather a demonstration program in the context of the ARV roll-out. Informed consent was not required by the Columbia IRB.
Antiretroviral Regimens
Upon enrolment, all participants were screened for HAART eligibility, defined from August 2003 to December 2004 as: WHO clinical stage 4 irrespective of CD4 T cell count; WHO stage 2 or 3 and CD4 T cell count ≤ 350 cells/mm3; or CD4 T cell count < 200 cells/mm3. These criteria were revised by the MTCT-Plus Initiative in January 2005 to be in compliance with WHO 2005 PMTCT guidelines and to avoid the side effects reported with NVP especially in pregnant women with CD4 T cell count > 250 cells/mm3 [18]; from that time forward, women with WHO stage 2 and CD4 T cell count < 350 cells/mm3 were no longer considered eligible for HAART.
Other criteria taken into account for deciding to initiate HAART were the absence of medical contraindications to HAART as well as major barriers to adherence. Pregnant women who met eligibility criteria initiated HAART as early as 24 wk of gestation according to the last menstruation date, usually with zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP). Treatment continued during labour and postnatally. Pregnant women who were not eligible for HAART received validated scARV prophylactic regimens, usually sc(ZDV+3TC) from 32 wk of gestation (until 3 d postpartum) and sdNVP in labour [9,19], or scZDV from 28 wk, or sdNVP alone, or both scZDV and sdNVP [4,7–9,20]. All infants received ZDV syrup for 7 d and sdNVP syrup on day 3 irrespective of the maternal drug regimen.
Follow-Up Procedures
Clinical classification using the WHO staging system was performed by the physicians at enrolment into the MTCT-Plus program and at each subsequent visit.
Women either used breast milk substitutes if feasible and affordable following WHO guidelines [21] or were encouraged to practice exclusive breast-feeding for a maximum of 6 mo and initiate early weaning from 4 mo onwards. Caesarean section was only performed for emergencies. Baseline adherence and psycho-social assessments were done before initiation of HAART, and followed by weekly visits for 8 wk using a standardized checklist of clinical symptoms to detect side effects and ensure adherence. A more detailed clinical evaluation, including symptom review, physical examination, and review of medication adherence was conducted monthly following MTCT-Plus clinical guidelines [22]. Adherence was assessed by physicians or nurses on the basis of a self report consisting of the number of pills taken by the women during the last 7 d preceding each schedule visit (all, most, few, none). Severe adverse events were classified according to international guidelines [23].
Laboratory Procedures
All blood samples of pregnant women who agreed to test were screened on site for HIV antibodies according to a validated algorithm described elsewhere [24]. CD4 T cell count was measured upon enrolment and at intervals of 6 mo. Hepatic and renal functions were measured prior to HAART initiation; liver function tests were repeated 2 wk after treatment initiation and monthly throughout pregnancy for women on HAART. Additional laboratory evaluation was restricted to patients with clinical indications.
Laboratory tests were done at a central reference laboratory (CeDReS, Abidjan) certified by regional and international quality assurance programs.
The CD4 T cell count and percentage were measured in the antenatal period at the enrolment visit and thereafter every 6 mo after the initiation of the treatment using a dual-platform flow-cytometry technique with an automated blood cell counter (MaxM, Beckman Coulter, http://www.beckmancoulter.com/) for absolute lymphocyte count and a flow cytometer (FACScan, Becton Dickinson, http://www.bdbiosciences.com/) for measuring the percentage of CD4 T cells (CD4%). Absolute CD4 T cell count was then calculated multiplying the CD4% by the total lymphocyte count. The laboratory quality control procedures included: (i) daily internal controls for both the automated blood cell counter (Coulter 5C cell control, Beckman Coulter) and the flow cytometer (BD multi-check control, Becton Dickinson); (ii) participation in two international assurance quality programs (UK-NEKAS and QASI).
Plasma HIV-RNA viral load (VL) testing for the early diagnosis of paediatric HIV infection was performed using a quantitative real-time RT-PCR technique targeted at the HIV-1 LTR gene as previously validated [25]. The quantification limit of this method was 300 copies/ml with 200 μl of plasma. All infants were tested at 4 wk of age, and if positive, confirmed with repeat VL testing at 6 wk. Infants with two positive tests were classified as infected peripartum. Infants with a negative VL test at 4 wk of age were classified as uninfected peripartum and were subsequently tested at 12 mo by rapid HIV antibody testing. If the antibody test at 12 mo was positive, we performed a second test for confirmation at 15 mo or later. The HIV infection status of the children who stopped follow-up just after being tested HIV antibody-positive at 12 mo or who had ceased breast-feeding under the age of 2 mo was confirmed by VL testing. HIV antibody-negative or VL-negative children were classified as uninfected. Postnatal transmission was defined as a negative HIV PCR from a first sample at age 30–180 d followed by a positive VL or antibody test at 12 or 15 mo.
Statistical Analysis
Group comparisons according to ARV regimens used Student t-test or nonparametric Mann-Whitney test for quantitative variables, and Chi2 test or Fisher exact test for qualitative variables. The first-live born child was used for analysis in the case of multiple births.
Two survival analyses were conducted using two different outcomes in children: HIV infection or HIV-free survival (which is defined as ending at the occurrence of HIV infection or death, whichever came first). Cumulative transmission risks of HIV and (HIV or death) were estimated using both Turnbull method and Kaplan-Meier probabilities. As results were similar (unpublished data), Kaplan-Meier estimates were retained to allow for comparisons between groups using the log-rank test. For survival analysis, time to infection was estimated up to the first positive test for peripartum cases or to the midpoint date between the last negative test and the first positive test for the postnatal cases. Results were expressed in percentages with their 95% confidence intervals (95% CIs). Determinants of HIV infection and (HIV or death) were explored using a Cox model with the following variables: maternal age, ARV regimen, WHO staging, CD4 T cell count, haemoglobinemia, infant feeding practice from birth, birth weight, and child gender. A stepwise descendant multivariate analysis included all variables with p < 0.25 in the univariate analysis. Statistical analyses were processed with Stata software, version 9.0 (Stata, http://www.stata.com/).
Characteristics of Study Population
Between August 2003 and April 2005, 261 pregnant women with confirmed HIV-1 infection were enrolled and 250 were prescribed ARVs before and/or during delivery: 143 (57%) received scARVs and 107 (43%) received a HAART regimen. Three of the original 261 women were lost to follow-up and eight delivered before an ARV regimen could be initiated (Figure 1).
Population included in the estimation of the rate of mother-to-child transmission of HIV in the MTCT-Plus program in Abidjan, Côte d'Ivoire, August 2003 through October 2006. Among the six HIV-infected infants, three had received single dose nevirapine (sdNVP), two short courses of ZDV+sdNVP, and one short course of ZDV+3TC+sdNVP for PMTCT.
Maternal baseline characteristics are summarized in Table 1. Overall, median maternal age was 27 y (interquartile range [IQR] 24–31 y) and median gestational age at the time of enrolment was 30 wk (IQR 25–33 wk). Median CD4 T cell count was 338 cells/mm3 (IQR 206–488 cells/mm3) and 44 (17.6%) of the women were classified as WHO clinical stage 3 or 4.
Maternal Characteristics of HIV-Infected Pregnant Women Having Initiated an ARV Regimen for PMTCT in the MTCT-Plus Program, Abidjan (Côte d'Ivoire), 2003–2005
HAART eligibility criteria were met by 104 women; in addition, three women received HAART at the discretion of the physician without fulfilling WHO/MTCT-Plus criteria. The median CD4 T cell count of all 107 women who received HAART was 189 cells/mm3 (IQR 135–266 cells/mm3); 33 (30.9%) of these women were at WHO stage 3 or 4, and 58 (54.1%) had a CD4 T cell count < 200 cells/mm3 (Table 1). Most (102 [95.3%]) received a combination of ZDV, 3TC, and NVP. Five women (4.7%) were prescribed stavudine (d4T), 3TC, and NVP (Figure 1). HAART was initiated at a median of 30 wk of gestation (IQR 27–33 wk) (Table 2). Median duration on HAART until delivery was 74 d (IQR 48–91 d). Of the 93 women treated with HAART ≥ 1 mo before delivery, 91% reported complete adherence. All infants born to HAART-treated women received sdNVP at 3 d of life and 1 wk of ZDV syrup.
Antiretroviral Drug Regimen Characteristics in Pregnant Women Enrolled in the MTCT-Plus Program in Abidjan (Côte d'Ivoire), 2003–2005
Among the 143 pregnant women who received scARV for PMTCT, the median CD4 T cell count was 467 cells/mm3 (IQR 368–602 cells/mm3) and 11 (7.7%) had WHO stage 3 HIV disease at the time of enrolment (Table 1). Median gestational age at prophylaxis initiation was 34 wk (IQR 32–36 wk) and median number of days on scARV drug regimens was 46 d (IQR 31–65 d) (Table 2); 103 women (72.0%) received sc(ZDV+3TC) with sdNVP during labour, 26 (18.2%) scZDV with sdNVP, and 14 (9.8%) sdNVP alone (Figure 1).
Among the 241 women who had pregnancy outcomes for the analysis (Figure 1), 172 (71.3%) initiated breast-feeding at birth (62 in the HAART group and 110 in the scARV for PMTCT group). The overall median duration of breast-feeding was 5.4 mo (IQR 4.0–6.8 mo) and was slightly longer in the scARV for PMTCT group (5.8 mo) than in the HAART group (4.6 mo) (p = 0.010).
Effectiveness of ARV Regimens at 4 Weeks and 12 Months
Excluding the second child of five multiple births, there were 241 pregnancy outcomes for the present analysis (Figure 1). Four (3.9%) and 6 (4.3%) stillbirths were reported in the HAART and the scARV for PMTCT groups, respectively (p = 1.00). HIV infection status could not be determined for six live-born children (three in each group), who died in the first week of life before a blood sample could be collected (Figure 1). Overall, among the 231 neonates at risk of HIV infection, 172 (75.1%) initiated breast-feeding, of whom 168 were tested for HIV at the age of 4 wk. Overall HIV infection status could be ascertained for 225 children (97.4%), among whom 12 were diagnosed as HIV-infected (Table 3): five were diagnosed by the age of 4 wk, three more by the age of 3 mo, and the remaining four by the age of 12 mo (Figure 2). The overall probability of confirmed peripartum HIV infection was 2.2% (95% CI 0.3%–4.2%): 1.0% (95% CI 0.0%–3.1%) in the HAART group and 3.1% (95% CI 0.1%–6.1%) in the scARV for PMTCT group (Table 4). At 12 mo, 5.7% (95% CI 2.5%–9.0%) of the infants were diagnosed as HIV-infected: 3.3% (95% CI 0.0%–6.9%) in the HAART group and 7.5% (95% CI 2.8%–12.3%) in the scARV for PMTCT group (log-rank test, p = 0.18). No statistically significant difference was found according to the infant feeding practice (p = 0.48). In multivariate analysis, low birth weight (<2,500 g) was the only factor associated with acquisition of HIV infection, with an adjusted hazard ratio of 5.63 (95% CI 1.62–19.49, p = 0.006), controlling for infant feeding practice, gender, maternal ARV drug regimen, WHO staging, absolute CD4 T count, haemoglobin level, and age at baseline.
Description of the 12 Cases of Paediatric HIV Infection in the MTCT-Plus Program in Abidjan (Côte d'Ivoire), 2003–2006
Profile of postnatal transmission study in the MTCT-Plus Program in Abidjan, Côte d'Ivoire, August 2003 through October 2006
*Upper limit of 95% confidence interval.
Kaplan-Meier Probabilities of HIV Infection in Children Born Alive and Probabilities of Acquiring HIV or Dying MTCT-Plus Program, Abidjan (Côte d'Ivoire), 2003–2006
Postnatal Transmission
The postnatal transmission risk was estimated among all children who were RT-PCR HIV-negative at age 4 wk (Figure 2). Subsequent pediatric diagnostic assessment was not possible for 21 children: 11 were lost to follow-up (ten in the scARV for PMTCT group and one in the HAART group), and ten had died (four in the scARV for PMTCT group and six in the HAART group). The definitive HIV infection status could not be determined for five children who were antibody-negative but still breast-fed at 12 mo of age. A total of 191 infants were thus included in this analysis (87 in the HAART group and 104 in the scARV for PMTCT group) including 138 breast-fed infants (52 in the HAART group and 86 in the scARV for PMTCT group). The median duration on HAART in breast-feeding women was 14.9 mo (IQR 14.5–16.2 mo) when the final paediatric HIV status was ascertained. Overall, four infants had a confirmed postnatal infection (2.3% [95% CI 0.8%–7.3%]). In the HAART group, one case of postnatal infection was identified among 52 infants (1.9% [95% CI 0.04%–10.2%]) breast-fed for a median of 4.7 mo (IQR 3.3–6.3 mo). In the scARV for PMTCT group, three cases of postnatal infection were identified among 86 infants (3.5% [95% CI 0.7%–9.9%]) breast-fed for a median of 5.7 mo (IQR 4.3–7.1 mo). If we hypothesize that the three cases with unknown timing are possible postnatal cases, the rate of postnatal transmission could be 3.8% (0.4%–12.9%) in the HAART group and 5.7% (1.8%–12.7%) in the PMTCT group. No case of postnatal infection was identified among the 53 infants who were formula fed (upper limit of 95% CI, 6.7%). One death of an HIV-infected formula-fed infant was reported (Table 5).
Description of the Occurrence of Pediatric Death in the MTCT-Plus Program in MTCT-Plus Program, Abidjan (Côte d'Ivoire), 2003–2006
12-Month Infant HIV-Free Survival and Death According to Maternal ARV Regimens
The overall probability of HIV infection or death among infants aged 12 mo of all women enrolled in this study was 11.7% (95% CI 7.5%–15.9%); the probability was 11.2% (95% CI 5.0%–17.4%) among infants born to HAART-treated women, and 12.1% (95% CI 6.4%–17.9%) among infants whose mothers received scARV for PMTCT only (log-rank test, p = 0.90) (Table 4). In multivariate analysis, two factors were associated with the occurrence of HIV infection or death (n = 231): low birth weight (adjusted hazard ratio = 3.71 [95% CI 1.53–9.03], p = 0.004) and female sex (adjusted hazard ratio = 0.35 [95% CI 0.14–0.88], p = 0.035), after controlling for infant feeding practice, maternal ARV drug regimen, WHO staging, absolute CD4 T count, haemoglobin level, and age at baseline.
A total of 18 deaths were reported in this cohort: of 99 infants born to woman who had initiated HAART during pregnancy, ten (10.1%) died, and among 132 infants who were born to women who received short-course antiretroviral prophylaxis, eight (6.0%) died. The data on infant mortality are summarized according to the maternal ARV regimen in Table 5. Twelve of the 18 deaths occurred in a medical facility where a plausible cause was recorded. Due to the intensive follow-up of mothers on HAART, eight out of the ten infant deaths in this group were documented, compared to only four of the eight deaths in the scARV for PMTCT group.
Maternal Adverse Events
As detailed in Table 6, nine (8.4%) of 107 pregnant women initiating HAART required one change to their ARV regimen before delivery. One woman was changed from NVP to efavirenz at week 6 of treatment (gestational age 32 wk) after diagnosis of tuberculosis. Eight women (7.5%) developed grade 3 or 4 adverse events attributed to HAART: five women developed grade 3 mucocutaneous rash attributed to NVP and were switched to nelfinavir, and two women developed grade 4 liver toxicity attributed to NVP, with alanine aminotransferase levels over 50 times and over 5 times the upper limit of normal value, respectively in the two groups of women; one woman developed severe anaemia attributed to ZDV. All events resolved with drug changes and no deaths were reported. In the cohort of women receiving scARV for PMTCT, no grade 3 or 4 toxicities were observed and no ART changes were made.
Pregnant Women Initiating HAART and Requiring ARV Drug Change before Delivery in the MTCT-Plus Program in Abidjan, Côte d'Ivoire, 2003–2006
Neonatal Adverse Events
As shown in Figure 1, the frequency of perinatal deaths (stillbirths and neonatal deaths in the first 28 d of life) was comparable in the HAART and scARV for PMTCT groups: 6.7% and 5.6%, respectively (p = 0.80). No significant difference in the rates of premature births (gestational age <37 wk) was noted between the two groups (7.8% and 7.9% respectively, p = 1.00). However, a higher proportion of low birth weight (<2,500 g) was observed in neonates whose mothers had received HAART, 26.3% compared with 12.4% among those having received a scARV for PMTCT regimen (p < 0.001). These differences persisted after adjusting for maternal body mass index, CD4 T cell count, and WHO clinical stage.
We evaluated a two-tiered PMTCT strategy in which treatment was selected based on maternal medical status (as indicated by CD4 T cell count and WHO staging) in a West African population. HAART was prescribed to pregnant women with advanced HIV disease who met WHO eligibility criteria based on their own health status, whereas short-course various combinations of ARV regimens for PMTCT were given to pregnant women with less advanced HIV disease, who did not qualify for HAART. Three-quarters of the infants were breast-fed, for a median of 5.4 mo. Overall, the rate of peripartum HIV transmission was 2.2%, the cumulative rate of infant HIV infection at 12 mo was 5.7%, and the 12-mo HIV-free survival was 88.3%, without measurable differences between the two groups.
The rate of peripartum MTCT that we observed in women on HAART was very low (1.0%), similar to rates reported from industrialized countries [2,3], despite a later identification of HIV infection during pregnancy, and a relatively short duration of HAART prior to delivery. In the Women and Infants Transmission Study in the US, HIV-1 transmission rate was 1.2% in infants whose mothers had received HAART but did not breast-feed [3]. Similarly, the European Collaborative Study Group reported the decline of MTCT transmission rates from 15.5% in 1994, to 5.1% in 1997–1998, and down to 0.99% in 2001–2002, i.e., when HAART became more widely used [2].
The maternal and PMTCT benefits of HAART initiated during pregnancy that have been described in the industrialized world may differ for populations from sub-Saharan Africa because of the wider spectrum of opportunistic diseases, the deeper level of immunodeficiency at which they occur [26], and the poorer nutritional background and obstetrical conditions. In the DREAM cohort in Mozambique where formula feeding was systematic, pregnant women initiated a ZDV/NVP/3TC HAART combination at 25 wk of gestation, irrespective of clinical or immunological staging; the rate of HIV transmission from mother to infant was 1.2% at infant age of 1 mo [27]. HAART was continued in this cohort up to 6 mo postdelivery for those not requiring therapy for their own health, while the others continued treatment indefinitely. We observed a comparable 1 mo of age rate of transmission with a more targeted prescription of HAART. As emphasized in the recently published WHO PMTCT guidelines, it is critically important that pregnant women who are eligible for HAART receive such treatment for the sake of their own health as well as for reducing MTCT [14]. Women with advanced HIV disease are at the highest risks both for HIV-related morbidity and mortality and for transmitting HIV to their child [28]. By decreasing the mother's plasma HIV VL and enhancing immune function, a targeted HAART both treats the mother's own HIV infection and reduces dramatically the likelihood of HIV transmission to the newborn. If HAART is used for PMTCT in women not requiring it for their own health, however, the potential risk to the woman's health of interrupting HAART after delivery and the potential risks of continuous HAART exposure to uninfected infants are unclear.
We observed low rates of postnatal transmission in both HAART-treated women and those receiving scARV for PMTCT only. These results were observed in conditions of short breast-feeding exposure with an overall median duration of 5.4 mo. We observed one case of postnatal HIV transmission among 52 breast-fed infants of HAART-treated mothers and 3/86 among the breast-fed infants of women on scARV regimens. There was no statistically significant difference between the two groups, although sample size was limited; this study was not designed to answer the question "does HAART substantially reduce postnatal transmission risk? While HAART might diminish postnatal MTCT because it suppresses cell-free HIV RNA in breast milk, other data counteract this hypothesis [29]. Further studies are needed to document the long-term safety and efficacy of HAART for the prevention of breast-feeding–associated HIV transmission, including among children breast-fed for long periods.
The universal use of HAART in HIV-infected pregnant women irrespective of their clinical or immune status could have several advantages, as shown in resource-rich countries. It avoids using scARV prophylactic regimens, which though effective in reducing MTCT, do not benefit the women's health and are associated with some risk of development of HIV resistance in the mother and infant, particularly with sdNVP [19,30]. However, in low-resource settings, many challenges hinder the universal use of HAART for all pregnant women, including limited access to ARVs, uncertain effects on maternal health from the short-term use of HAART with postpartum interruption, and toxicity concerns about NVP-containing HAART in women with higher CD4 T cell counts [18,31]. It is therefore reassuring that the selective use of HAART by HIV-infected pregnant women with advanced disease, and scARV for PMTCT by pregnant women with less advanced disease yield equivalent results in terms of HIV-free survival in their infants. Furthermore, the use of a ZDV+3TC postpartum "tail" for 7 d reduces the risk of acquiring viral resistance in women receiving scARV for PMTCT including sdNVP [19,32].
We observed a relatively low rate of severe adverse events in HAART-treated HIV-infected pregnant women. Adverse events that did occur were rapidly resolved with appropriate drug management, and unexpected toxicities were absent; together these observations suggest that HAART during pregnancy for women with advanced disease is reasonably safe. Of note, this study did not address the question of the use of NVP-based HAART in women with high CD4 T cell counts. The fact that 7.5% of the women developed toxicities requiring a change of ARV drugs highlights the importance of careful monitoring of pregnant women on HAART. Clinical monitoring can detect many adverse events even without laboratory results: in this study mucocutaneous rashes constituted more than two-thirds of the maternal adverse events, and one woman had severe anaemia with associated clinical symptoms. However, the diagnosis of severe liver toxicity requires frequent laboratory monitoring during pregnancy. Previous reports on adverse events in pregnant women in Mozambique [15], Kenya [33], and Thailand [34] noted that rates of serious hepatic or cutaneous adverse events among pregnant women receiving NVP-containing HAART were comparable to those observed in nonpregnant individuals. Liver toxicity, as indicated by serial liver function tests, was reported in 6.3% of 606 women in the DREAM cohort who were systematically treated by HAART in Mozambique [35]. In our study, we found a rate of 2% of liver toxicity in HAART-treated pregnant women with advanced disease.
We also found that the rate of low birth weight in infants born to mothers treated with HAART was significantly greater than among those exposed to scARV regimens for PMTCT. HAART exposure has been associated with prematurity in some series [16,36] while other studies have found no association [37,38]. Low birth weight might be related to the fact that the mothers had more advanced HIV disease, rather than being a direct effect of HAART itself. Further assessments of these infant outcomes are underway in our cohort [39].
The main limitation of our study is the cohort sample size, with relatively small numbers per treatment group, thus affecting the precision of some MTCT rates and the power to fully perform statistical comparisons between groups. However, we were able to document that the upper confidence limit of the cumulative MTCT rate at 12 mo was less than 7% in the HAART-treated population where breast-feeding was commonly practiced for 5 mo, whereas natural risk may have exceeded 30% [10,11]. Also this study is not a comparative study, but a description of two tiers with one group receiving HAART and another group a short-course of ARVs for PMTCT based on HIV disease staging. Thus, comparisons between the two tiers should be interpreted with caution. A more convincing group for the comparison would be a group of HIV-infected pregnant women eligible for ART who did not receive it. However, it would be unethical to perform such a study in a setting where HAART is available for women who meet eligibility criteria.
Our team has recently summarized available historical data on HIV-infected pregnant women eligible for ART in the same Abidjan population [40]. We estimated the transmission rate at 6 wk at 26.2% in such women having received antepartum a short-course regimen of 4 wk of ZDV alone and practicing predominant breast-feeding. In a comparable group of ART-eligible women who had received 4 wk of ZDV and sdNVP, with short-term breast-feeding, this rate was 10.1%. At 6 mo the corresponding transmission rates were 41.6% and 15.9%, respectively. It is important to note that, in the current study, the infant HIV-free survival rates in the two groups was 11.2% (HAART tier) and 12.1% (scARV tier), not different between infants born from women with high or low risk of HIV transmission. It remains unclear, however, whether the benefits of maternal HAART were counterbalanced by their effect on infants such as early neonatal death in association with prematurity.
This study has several strengths. First, retention was high, with the final HIV status available in more than 86% of live births and only 2% of infants lost to follow-up among HAART-treated mothers. Second, the high level of adherence achieved is a likely explanation for the low rate of MTCT in the HAART-treated tier. Finally, we demonstrated that it is feasible to screen pregnant women for HIV, assess disease status by performing CD4 T cell counts, and quickly initiate HAART. Those who did not require HAART were treated with standard scART regimens for PMTCT, and the vast majority of women and their families were engaged in long-term HIV services. This outcome further demonstrates that PMTCT is an excellent entry point for women and families in HIV care and treatment.
In summary, a two-tiered approach to PMTCT, in which pregnant women with advanced HIV disease receive HAART, and those with less advanced disease receive scARV regimens for PMTCT, was safe during pregnancy and highly effective for the prevention of peripartum and postnatal transmission in an African population. While further investigations in other larger or pooled studies are needed to further explore the balance of benefits and risks related to HAART in breast-feeding mothers, our results provide evidence supporting the most recent WHO guidelines [14]. n
Supporting Information
Alternative Language Abstract S1. Translation of the Abstract into French by François Dabis
Text S1. IRB Approval
Ministry of Health of Côte d'Ivoire: National Ethic Committee consent letter.
Text S2. Columbia University Medical Centre IRB for the MTCT Plus Initiative
Text S3. Columbia University Human Subjects Protocol Data Sheet
Text S4. IRB Supporting Letter
The authors thank Laurence Dequae-Merchadou for her help with statistical analyses. The authors also thank the Secretariat of the MTCT-Plus Initiative at Columbia University, the ACONDA Côte d'Ivoire team, the CeDReS team, the ANRS Ditrame Plus study clinic team, as well as all patients and families enrolled in this program. Didier Ekouevi was a fellow of the French Charity Sidaction and is a fellow of the European and Developing Clinical Trials Partnership (EDCTP). FR was supported by the French Ministry of Foreign Affairs. RB was a fellow of the French Ministry of Education, Research and Technology and is now a fellow of the French Charity Sidaction. This study was reported in part at the 12th Conference on Retroviruses and Opportunistic Infections, 22–25 February 2005, Boston (Abstract 785) and at the 3rd International AIDS Society on HIV Pathogenesis and Treatment, 24–27 July 2005, Rio de Janeiro, Brazil (Abstract TuFo0202).
Author Contributions
BTG, DKE, WMES, and FD designed the study. BTG, DKE, PAC, VL, and EJA analyzed the data. BTG, IV, CAB, and ST enrolled patients. BTG, DKE, CAB, PAC, RB, VL, WMES, EJA, and FD contributed to writing the paper. BTG collected data/performed experiments. IV monitored the study, supervised the study team, and contributed to the event documentation committee. CAB was responsible for the coordination of the MTCT program in Abidjan. FR was responsible for all biological activities carried out in the CeDReS laboratory (Abidjan, Côte d'Ivoire).
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Dr. Caroline Rhoads reviews medical content for Healthwise, a nonprofit organization with a mission to help people make better health decisions. Dr. Rhoads is an associate professor of medicine at the University of Washington in Seattle and is actively involved in teaching residents.
MD: University of Pennsylvania, Philadelphia, PA, 1989
Internship in Internal Medicine: University of Washington Affiliated Hospitals, Seattle, WA, 1989-1990
Residency in Primary Care: University of Washington Affiliated Hospitals, Seattle, WA, 1990-1992
Chief Resident in Primary Care: University of Washington Affiliated Hospitals, Seattle, WA, 1992-1993
American Board of Internal Medicine
University of Washington School of Medicine, Seattle, WA
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Thoughts on War
Jefferson was a law student at the College of William & Mary when he stood at the doors of the House of Burgesses enraptured listening to Patrick Henry present resolves against the Stamp Act. When he himself was a burgess, he continued to promote the idea of revolution. Jefferson served as Governor of the Commonwealth of Virginia and President of the United States.
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Mr. Jefferson, what do you say to someone who's going to war?
The question stunned me. In more than ten years of portraying Thomas Jefferson at Colonial Williamsburg, where our own Revolutionary War is referred to nearly every day, I had never been asked that question. The query came from a seven-year-old girl, perhaps possessing wisdom beyond her years.
As she gazed intently at me, I frantically tried to recall something of Jefferson's wisdom that would be appropriate. I remembered quickly that Jefferson, as the third president, was the first chief executive of the United States to send soldiers abroad to fight for our freedoms - a decision that was extremely difficult for him.
"I abhor war and view it as the greatest scourge of mankind," Jefferson wrote. "The evils of war are great in their endurance and have a long reckoning for ages to come." With the dispatch of American troops to fight on foreign soil, Jefferson realized that defending free trade among nations was vital to the preservation of our own freedoms, newly won a generation before.
The path to war in 1801 was convenient. Not only was the cause morally and ethically right, it was popular. "Millions for defense, not a penny for tribute," was the battle cry in the streets of America and in its newspapers. No doubt remembering his own words, written on the eve of our revolution,"We are alarmed here with the apprehensions of war and sincerely anxious that it may be avoided, but not at the expense either of our faith or honor."Jefferson ordered the U.S. Navy and Marine Corps against the pirates of the Barbary Coast, the terrorists of his day, that had for centuries exacted monetary tribute - ransom - as they preyed on the shipping of the world's maritime nations.
Jefferson's war against the Barbary pirates was also a war between the United States and the Islamic kingdoms of North Africa, which sheltered the pirates, Tripoli, Tunis, Morocco, and Algiers. In answer to cries of injustice towards a people of differing religious opinion Jefferson had always said,"If ever there was a holy war, it was that which saved our liberties and gave us independence."This history lesson, however, would be of little concern to the young girl standing before me intent upon an answer. Puzzled how I might answer her in clear and simple Jeffersonian terms, I considered,"If we are forced into war, we must give up political differences of opinion and unite as one man to defend our country. But whether at the close of such a war, we should be as free as we are now, God knows."In these fleeting moments, I realized Mr. Jefferson must have faced a similar question, especially as he was often surrounded by children and grandchildren. Suddenly, history appeared lateral to me, and I answered her with my own thoughts and words as best I could imagine Mr. Jefferson responding.
"We should tell our soldiers going to war that we are with them in our hearts and in our minds, that we will not forget them, as we know they will not forget us. And we wish them to return to us safely as soon as possible."
Bill Barker interprets the character of Thomas Jefferson for Colonial Williamsburg.
Read more about Bill Barker on NPR's "War Diaries"
See Thomas Jefferson, Man of the Millennium


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View of the west face of North Guardian Peak in the Kolob Terrace section of Zion National Park.
For more photos check out JonJasper.com
Many panoramas of Zion National Park's trails, views, canyons, and peaks. Zion National Park is known for it large exposure of the Navajo sandstone's steep red walled cliffs and world classic canyons and canyoneering routes.


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U.S. Equal Employment
Opportunity Commission
Companies Punished Woman for Filing Discrimination Charge, Federal Agency Said
HOUSTON - A Houston-based oil company and a Wisconsin-based energy and manufacturing company will pay $62,500 and furnish other relief to settle an employment discrimination lawsuit filed by the U.S. Equal Employment Opportunity Commission (EEOC), the agency announced today. The EEOC had charged that both Vitol, Inc. and Johnson Controls, Inc. were responsible for unlawfully firing an employee for filing a sex discrimination charge against Vitol.
The EEOC's suit was filed in U.S. District Court for the Southern District of Texas, Houston Division (Civil Action No. 4:11-cv-03506). The EEOC said that after serving as executive secretary to the president, Lucinda Gonzalez was fired by Vitol in July 2008 and subsequently hired by Johnson Controls as a sales assistant. In December 2008, Gonzalez filed a charge of sex discrimination with the EEOC in good faith against her former employer, Vitol. Shortly after receiving a copy of the charge and learning that the EEOC would not be investigating it further, Vitol forwarded a copy of the charge and the EEOC notice to management at Johnson Controls, where Gonzalez was employed at the time. According to the lawsuit, on the very same date that the charge and dismissal were received by Johnson Controls and reviewed by her supervisor, that company made the decision to fire Gonzalez as part of a purported reduction-in-force.
The EEOC argued that both companies' actions were retaliatory -- Vitol, by forwarding the charge to Gonzalez's new employer, and Johnson Controls, by acting on the information that Gonzalez had filed the charge by terminating her employment.
Retaliation against an employee for complaining about discrimination violates Title VII of the Civil Rights Act of 1964. The EEOC filed suit after first attempting to reach a pre-litigation settlement through its conciliation process. The suits were settled by two separate consent decrees signed by Judge David Hittner.
Under the Vitol Decree, the company agreed to pay $62,500 in monetary relief to Gonzalez; provide her with a neutral job reference when requested by a prospective employer; and keep confidential all documents relating to this suit and the underlying charge and investigation. Additionally, among other things, Vitol agreed to implement and/or enforce policies prohibiting workplace discrimination and retaliation and to specifically address, through professional training, the issues of employment discrimination, harassment and retaliation with all managers, supervisors and officers. The Vitol decree is effective from the date of entry through Dec. 31, 2013. Judge Hittner signed both decrees late Friday, August 31, 2012.
Under the Johnson Controls decree, to be effective for 18 months, the company agreed to injunctive and non-monetary relief, including the separation of documents pertaining to the lawsuit from Gonzalez's personnel file and the provision, upon request, of a neutral employment reference. Additionally, Johnson Controls is required to provide training on employment discrimination and retaliation to its management and non-management employees at its West Little York Road branch; maintain and enforce policies which prohibit discrimination and retaliation in the workplace; and post a notice of non-discrimination in a location readily and normally accessible to employees.
"Employees must be assured unfettered access to the remedial mechanisms provided by the EEOC to address discrimination in the workplace," said Jim Sacher, the EEOC's regional attorney in its Houston District Office. "Even if a charge, made in good faith, is not pursued, an employee must be protected from adverse action for filing the charge. When the EEOC brings suit, it does so in the public interest, specifically so as to enlighten both employers and employees of the retaliation provisions of federal anti-discrimination law. For that reason, the non-monetary provisions, including those pertaining to policies and workplace training, are vital pieces of each settlement."
Connie Wilhite, the EEOC's senior trial attorney in Houston, said, "Even if the EEOC chooses not to pursue an investigation of a charge, an employee's right to file such a charge must remain unimpeded. This is mandated by well-established public policy which provides that the EEOC act on information contained in a charge not just for the benefit of the specific discrimination victim, but also to vindicate the public interest in preventing employment discrimination."
Vitol Inc. is a Houston-based company, incorporated in Delaware and a subsidiary of a multinational energy conglomerate, Vitol Group. According to the parent company's website, www.vitol.com, Vitol Group is a publicly traded "major oil multinational" company and "one of the largest traders in the world's energy marketplace."
According to its website, Johnson Controls is a global energy company offering products and services to optimize energy and operational efficiencies of buildings, automotive batteries and interior systems for automobiles.
The EEOC is responsible for enforcing federal laws against employment discrimination. Further information is available at www.eeoc.gov.


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Broomfield, CO - May 22, 2013
Webroot, a leader in cloud-based security intelligence solutions, today announced the appointment of Stan McKee to its board of directors. McKee will also chair Webroot's audit committee.
"Stan's deep knowledge of technology, along with his business and financial expertise, make him a wonderful addition, and we are extremely pleased to welcome him to our board of directors," said Dick Williams, chief executive officer at Webroot. "His strategic guidance, coupled with his mentoring of our finance team, will be invaluable as we build upon Webroot's market leadership and expand globally to meet the growing demand for our innovative cloud-based security intelligence solutions."
Until his retirement in 2002, McKee served as executive vice president and chief financial and administrative officer at Electronic Arts Inc., a publicly-held company that develops and publishes interactive entertainment. Under his leadership, Electronic Arts had unprecedented growth, expanding its sales revenue from $50 million to $2.5 billion. Prior to joining Electronic Arts, McKee was chief financial officer at Digital Research, Inc., a privately-held developer of operating systems, computer languages and applications. In addition, he served in the consulting division of Arthur Andersen for seven years.
"Webroot is taking a unique approach to protecting companies and consumers from today's most challenging malware threats and has produced a truly innovative solution that leverages two of the most significant technology advances of the past decade – the cloud and security intelligence," said McKee. "Businesses and users across the globe are rethinking their security strategy to better protect their corporate and personal data against cybercriminals, and Webroot has positioned itself perfectly as a leader in the market. I look forward to working alongside some of the industry's most innovative security leaders to further accelerate the company's rapid growth and visibility."
McKee has been a member of Leapfrog's board of directors and chair of the audit committee since November 2003. He also served as a director and audit committee chairman of ArcSight, Inc., a publicly-held company that provided security and compliance management software and appliances to government and commercial entities, from February 2005 until its acquisition by HP in 2010. McKee has served on numerous other private company and joint venture boards. He earned a B.A and an M.B.A. from Stanford University.


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If you love popcorn, congratulations; today is for you. Popcorn has actually been around for thousands of years - in Mexico, popcorn remnants at least as old as 3600 BC have been discovered. Popcorn gained the popularity it enjoys today much later, however. As a result of the great depression and sugar rationing during WWII, popcorn rapidly became a favorite snack among Americans, and with the invention of the popcorn machine, became the choice movie theater snack as well. So, go on, celebrate, and pop a few kernels.
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Superior sound quality backed by technology from the Yamaha professional MG166C live sound mixer.
Whether you have a mixing application that involves only a few channels, or up to 32 inputs with substantial signal routing versatility, Yamaha's MG series offers a console that will give you the capacity, control, and performance you deserve. All models are remarkably compact and lightweight for superior handling and portability, but absolutely no compromises have been made in terms of features, performance, or durability. The MG mixers offer an extraordinary blend of technology: some inherited from professional Yamaha mixing consoles you're likely to see in distinguished halls throughout the world, and some developed specifically to deliver optimum performance in the MG-console format. In either case these performance-packed Yamaha mixers are founded on a world-spanning network of human and technological resources that crystallize to deliver features that really matter, and sound that is undeniably superior.
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Power consumption: 30W
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Accessories: Owners manual, AC adaptor


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so i have a dedicated firewall up connected to my internet. on the inside i have subnet 192.168.0.0 with the firewall as a dchp server and then my home router using the firewall as a gateway. the home network subnet is 192.168.1.0 so just in case your still not following
internet --> dedicated firewall (.0.1) --> (.0.200) home router (.1.2) --> home computers (.1.x)
i can get internet, and i had some people test it and port forwarding works so that people can access the server on my home network, but when im logged into the server, i cant ping anything inside my homenetwork. also, when i try to access my server as if from an outside host (using my external ip) i get timeouts. whats up? i have no idea on this one
what ive tried:
taking down my router firewall
Code:route add -net 192.168.1.0 netmask 255.255.255.0 dev eth0and thats about it... so any help would be greatly appreciatedCode:route add -net 192.168.1.0 gw 192.168.0.200 netmask 255.255.255.0 dev eth0


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Bob Marley, original gangsterMonday, August 3rd, 2009
The father of modern reggae music, Robert Nesta "Bob" Marley, is still pushing musical boundaries and inciting controversy 28 years after his death. In a break with his promotion of Rastafarian beliefs, a newly released single entitled "You Know You're a Nigga" reveals his support of underground gangster rap years before its inception.
"This is some crazy shit," said Jesse Weaver of Jive Records, the label responsible for the song's release.
Weaver and a crew of PR agents held a press conference earlier today to discuss the song. In attendance was Rita Marley, the sole owner of her husband's work and long-time holdout to the song's release.
"I'm not going to lie–I listen to this song every day," said Marley. "I finally decided it was time the public see my husband in a new light."
"We're proud to be putting out this track," said Weaver. "It makes me look at his entire catalog with a gangsta lean," said Weaver.
Marley went on to describe her husband as a "complex, multi-faceted man" who at one point "really did shoot a sheriff."
"It wasn't just peace and hugs," she said. "It was also his piece and thugs."
In only one day of sales, "You Know You're a Nigga" has topped sales charts and received nearly continuous air play.
"We're confident this will cement Bob's legacy as an early gangster rap crossover artist," said Weaver.
The new single has generated controversy as well, due largely to its repeated use of the N-word. Several major retailers have pulled the album from their shelves due to complaints and petitions from angry parents and church groups.
Weaver was incredulous when questioned about the push-back.
"How many times must a brother in America have his album pulled? I mean, this is so hot, so hot," he said.
"So hot, so hot," added Marley.


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Welcome to Firewalls.com
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Photo by Dave Mayo
BANNER ELK, N.C. --- The Lees-McRae College women's basketball team placed four players in double figures, and converted 23-of-27 chances at the free throw line to rally for a 64-57 win over Young Harris College in non-conference play on Tuesday evening in Williams Gymnasium.
The win marks Lees-McRae's (2-2) second straight victory, as the Bobcats converted 85 percent of their attempts from the free throw line, and knocked down 40.9 percent of their attempts from the floor in the second half. Young Harris (0-2) posted a field goal percentage of 47.1 percent in the contest, including a 59 percent clip in the first half, while edging the Bobcats on the glass by a 29-27 margin.
The Bobcats converted 29 Mountain Lion turnovers into 29 points in a game that featured nine ties and 17 lead changes, with no margin ever surpassing eight points.
Lauren Lewis (Concord, N.C.) paced the Bobcats with 14 points on 4-of-7 shooting from beyond the arc, as Kerri Belcher (Roanoke, Va.) added 13 points, five rebounds, four assists and a career-high seven steals.
Layana De Souza (Rio de Janeiro, Brazil) and Kabrina Truesdale (Wilmington, N.C.) each tallied 12 points, while Truesdale chipped in five steals. Truesdale and Alyssa Munson (Summerfield, N.C.) chipped in game-highs of five assists and six rebounds, respectively.
Peyton Robertson led the way for Young Harris with a game-high 16 points, adding contest-bests of six boards and two blocks, while Lauren Smith added 11 points and four steals. Shaquaya Daniels chipped in nine points and three assists.
Young Harris jumped out to an early 7-5 lead before the Bobcats responded, launching a 12-6 run to claim a four-point advantage on a Lewis triple with 11:15 left on the clock. The Mountain Lions countered with a 12-3 spurt of their own, opening a 25-20 margin following a Smith jumper at the 7:31 mark.
The Bobcats battled back with a 9-6 stretch over the final seven minutes of the period, closing the gap to 31-29 heading into the intermission on a trey by Lewis. After Young Harris opened the half with two quick buckets, Lees-McRae countered with an 11-4 spurt, claiming a narrow 40-39 lead following a Belcher lay-in with 11:32 to play.
The teams would trade the lead several times over the next few minutes, with Young Harris taking a 47-44 advantage on a put-back by Kaycee Cash at the 8:32 mark. Lees-McRae responded with some superb free-throw shooting, converting nine of their next 10 freebies to open a 55-51 lead with 5:10 left on the clock.
The Bobcats would hold on from there, limiting the Mountain Lions to three points in the final four minutes as Natalija Cakarevic (Belgrade, Serbia) capped the night's scoring with her team's final five points, including a clutch three-point play at the 2:22 mark.
Lees-McRae returns to the court on Saturday when the Bobcats complete the away leg of the home-and-home series with Young Harris at 2 p.m. in Young Harris, Ga.


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The Hotel Location Ischia Island The Restaurant
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Wall Street Pay Tracker for 2012
Most of the biggest bank's in the country have now released the paychecks their CEOs took home for 2012 and the trend is higher.
Sure there are a couple of nattering nabobs of negativism that cut pay, but overall pay still looks rather healthy and no one is making just $1 anymore.
Here's a recap of the big checks announced so far.


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While the fact that I, as an atheist, marrying a christian was a sure fire way to lead to disagreements it went a bit too far today.
She has spending each day at a ongoing church revival for the last two weeks. Today I finally raised a bit of concern for just how much time she was spending there each day (from about 10am to 3pm and then 6pm to 11pm each day). Her response was something that I have never experienced before - She "rebuked me in the name of Jesus", called me a devil and proceeded to follow me around the house talking in tongues. WTF! How is that any different then a small child sticking their fingers in their ears and saying "nanana I can't hear you!"? To me that is just incredibly disrespectful and dismissive as if anything said couldn't possibly be from a spouse but had to be the boogieman.
Views: 2220
Disturbing .... :(
Hello, I am also an atheist marred to a christian.
While my wife is no where near as fundamental some things remain the same.
Main thing is the kids come first. Both should be able to agree to discuss this difference away from the kids.
You don't want her going nuts in front of them and I'm assuming she does not want them to see you responding to her nuttiness...
that settled
She is spending to much time at church and it is not healthy(really who would tell her to talk in tounges at you? and support her in doing that?)
so Simply request less time and church and maybe suggest more time reading the bible. It's the word of her god and may represent a compromise. You may have to offer to read it yourself...bring your observations to her and maybe she will see it's a book...nothing more..
Or if she persists she knows you have read the bible...and for some reason that matters.
I think it might be intervention time....
So sad, especially for the kids.
© 2020 Atheist Nexus. All rights reserved. Admin: The Nexus Group. Powered by


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Because the growth rate in Telangana was high he quickly concludes that Telangana is doing much better than rest of AP. Detractors of Telangana are using his observations to say that Telangana has never been discriminated - and in fact it developed more and better than rest of AP.
Here are three different countries with GDP growth rates for year 2007.
More importantly, percentage increase can become an extremely flawed statistic if you don't know how to interpret it - as shown above.
SriKrishna Committee will surprise you
My only word of advice: Beware.


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9 September 2013 at 4.58pm | 4 Comments
The Royal Opera's spectacular production of Puccini's Turandot was presented in 1984 as part of the Cultural Olympics in Los Angeles. It is now a signature production of The Royal Opera: performed almost a hundred times at the Royal Opera House as well as around the world. For this new revival, writer, lecturer and broadcaster Sarah Lenton has been finding out about the immense amount of work behind the scenes to bring it to the stage.
It's July 2013, and the Royal Opera Chorus are already being fitted for their Turandot costumes before the summer break. Colin Maxwell (the Production Manager) has been down to the scenery store in Wales to check out the Emperor's throne, and Kate Flatt (the Turandot choreographer) is wondering whether anyone's told the singer playing Turandot that she's going to be carried in on a litter. 'That's how Gwyneth Jones [in Los Angeles] did it, and it looks incredible – a great icon being carried in. Incredible and imposing.' Which rather sums up the Royal Opera House production of the opera itself.
'Imposing' is obvious. Terry Fitton (Stage Props) knows this production well: 'The thing about Turandot is that there are not a lot of props compared to, say, La bohème, but they are big. I mean they are big. The dragon cart is very large, very awkward to manoeuvre, but quite magnificent to look at. We have to build it and put it together with that huge grind-wheel, and then manipulate it into position. It's tricky because you have such a narrow entrance – but it is a magnificent beast.'
But 'incredible'? Well, this production has been performed over ninety times since it was first seen at the Royal Opera House in 1984, it's been played at Wembley Arena, and toured the world (Los Angeles, Seoul, Tokyo, Parma, Cagliari, Lisbon, Madrid and Washington) yet it always appears on the main stage looking as fresh as paint. One of the reasons for this must be the omnipresence of the original designer and choreographic team: Colin Maxwell checked out the Emperor's throne because: 'Sally Jacobs (the designer for Turandot) is always concerned about it – it has its own crate, but every trip it gets damaged. Sally's been coming back for 30 years. Which is brilliant and largely why the show keeps so fresh. Her eye is always on it.'
Terry Fitton knows that Sally will be glancing in his direction as well. The great Turandot masks slung from the balcony with their grotesque streamers of blood, are obviously difficult to manoeuvre, but that's all in a day's work – the real problem is the streamers: 'The stage crew have to put the masks on the set – they're on five-metre poles and top heavy. So there you are at the bottom trying to pass one up to someone and if you lose control it will all come crashing down (but that's never happened!); the big job is to make sure that those red ribbons are nice and loose and not tangled in knots. The hair is made of raffia, fire-proofed of course, and it all has to be tidy.'
This extract is taken from Sarah Lenton's article 'Fresh as Paint'. The full article can be found in the Turandot programme book, available in the theatre at performance times and from the ROH Shop.
Turandot runs from 5 July–16 July 2017. Tickets are still available.


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5 Intelligent Promotion Strategy for Your Legal Site
Buses and benches have their time, but now the internet is the best place to reach potential clients. What promotion strategies can you use to bring people to your legal website?
Legal marketers face many problems, but increasing your online presence can handle it.
This article will provide you with a strategy to extend the reach of your legal website. Once you get more traffic, you can start turning those prospects into paying clients.
Take a look at your current marketing strategy, and let's make improvements.
Optimize Mobile
So many companies optimize their website for mobile users now that people are expected. They will go to other sites if your site is not optimized.
Create responsive designs for your website. It will analyze what tools visitors use and adjust their layout.
Google likes websites that consider usability. The right mobile optimization increases your SEO value.
Content Marketing
If you have read an informative blog, you benefit from content marketing.
Unlike annoying and annoying ads, content marketing focuses on delivering value to consumers. With an informative blog, you can create a very helpful reputation with prospective clients.
Content marketing also increases your SEO value by building links and keywords.
Content marketing is more than 60% cheaper than other promotional strategies. Plus, it generates three leads.
Overall, it provides valuable information and directs them to your legal site. It will generate more prospects than annoying them with ads.
Social media
Social media is very important to spread your online presence. You've put your audience on, so search for the social media they use.
The legal industry can confuse the average person. Social media is the best way to answer their questions with valuable information.
It also gives them a way out to share a great experience with your firm.
You want to involve people. Consider asking their opinion about the hot button topics related to your service.
In the era of everything online and on demand, clients want 24/7 access for you. If they see your website or social media, they want you to answer their questions immediately.
One of the best promotional strategies is referrals. Provide experience on websites that you'll be happy to refer to.
For example, industry leader Babcock Partners has a live chat function on their site. If the client has any questions, Babcock Partners can respond immediately.
Automated Promotion Strategy
Your marketing team should not waste their time sending out hundreds of emails. Automate your marketing process wherever you can.
Many services exist to send emails automatically. That way, leads get a welcome welcome email when they sign up for your email list.
You can also program automatic social media posts. Your team can spend more time replying to comments than posts.
Interesting Together
Promoting your legal site involves a complete presence on the internet.
You can not just blast people with ads and expect traffic. With tactics such as the presence of social media and content marketing, you can generate organic traffic to your website.


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We have a variety of experienced designers specialising in different areas of the web and internet available to help you with your project, no matter how big or how small this may be. We can call round to your premises to discuss your requirements or you can call in and see us at our office. So, pick up the phone and give us a call to make an appointment, or email us at
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Tiny Dancers in Studio with Sheila (Daphne Rubin-Vega)
Join us! theindependentcollective.com/join @TICNYC facebook.com/theindependentcollective We are currently crowdfunding for the film Tiny Dancer by Jayce Bartok and produced by Tiffany Bartok. Tiny Dancer is about a legendary principal dancer and new mother (Katherine Crockett – The Curious Case of Benjamin Button), who struggles to balance her drive for perfection on her journey to find happiness. Also starring is Daphne Rubin-Vega (Jack Goes Boating, Rent) who will next be seen in the Broadway production of Streetcar Named Desire. TIC is proud to collaborate on Tiny Dancer with Desmond Richardson of Complexions Dance Co. Tiny Dancer is a sponsored project of the New York Foundation for the Arts (NYFA), a 501(c)(3), tax-exempt organization. Contributions on behalf of Tiny Dancer must be made payable to the New York Foundation for the Arts, and are tax-deductible to the extent allowed by law.


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Krisjanis Kaktins-Gorsline
Canadian, b. 1980
need eep, 2006
oil on birch plywood
76.2 x 61 cm
Collection of the Winnipeg Art Gallery; Acquired with funds from the Estate of Mr. and Mrs. Bernard Naylor and with funds from the Canada Council for the Arts Acquisition Assistance program/Oeuvre achetée avec l'aide du programme d'aide aux acquisitions du Conseil des Arts du Canada
Painting, Canadian Contemporary (1980-present)
A graduate of the University of Manitoba's School of Art and Columbia University, Krisjanis Kaktins-Gorsline follows in many ways the Surrealist Prairie tradition established by artists such as Kenneth Lochhead, Ivan Eyre, and Esther Warkov. Kaktins-Gorsline's paintings are an exotic mix of the grotesque and beautiful. Finding inspiration in fragments of experience both real and imagined, when Kaktins-Gorsline starts a work he never really knows how it will turn out. Animated, child-like, and yet uncanny, need eep evokes uncomfortable feelings and makes searching for meaning and understanding difficult. In this painting, gender and age are disguised; half-human and half-something else, a pathetic character stands knee deep in water, underwear sagging, hunched over in resignation to the entrails exploding from his stomach.
Gallery Hours
- Tuesday 11am-5pm
- Wednesday 11am-5pm
- Thursday 11am-5pm
- Friday 11am-9pm
- Saturday 11am-5pm
- Sunday 11am-5pm
- Closed Monday


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Haven't been posting much...
...but I have been reading and trying to comment at least a little.
When I wrote my last post, I thought I'd have a couple new posts coming but I really didn't have anything to write. I thought of the blog and my mind went blank. Maybe this "I donno what to say" entry will spark a bunch of things to say like my last such post... Hopefully!
But it's different now than it was then. I've just been exhausted from my daughter being sick... I still haven't regained my appetite. If anything I have been eating less now than I did when I was at the hospital all day. Maybe it's because there was nothing to do there so whenever I had a chance to leave the room it was to eat, hungry or not. I just weighed myself for the first time in a while and I have lost about 6 pounds. Might not seem like much but I haven't been trying and I'm on the skinny side of a healthy weight for my height. I hadn't thought about weight at all so I was really surprised when I weighed myself and found that. I guess if I had been thinking about it I wouldn't be surprised much by the weight loss since even I know I have been eating less and been under some stress.
Funny how the scale came out at my parents'. My brother was telling my husband he couldn't eat the whole lasagna he had ordered for himself and of course my husband said he could (I was like... duh, of course he can!) and they weighed it. It was a kilo they said (the scale is in pounds so I guess they converted that themselves). Anyway, he ate it all.
About Islam, I have been thinking about God and Islam constantly lately. Funny that I can't think of anything to post when I'm thinking about Islam the most. I prayed the afternoon prayer and I will pray the night one soon, I think. I hadn't in a while... I don't know if I will keep up at least a prayer per day, but I hope to. I am trying to get my husband to pray too but I don't think he's there yet. I will try to update about my Islam at least, even if I find no interesting topics to write about.
Thanks for reading.


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Redskins' Alfred Morris — 'Signing Contract Better Than Spending Money'
In a normal NFL year, Redskins running back Alfred Morris would have been a leading contender for Rookie of the Year. But with teammate RGIII's sensational debut behind center and Andrew Luck and Russell Wilson making headlines at quarterback, Morris had to be content with being named to the Associated Press All-Pro team.
The sixth-round draft pick out of Florida Atlantic helped lead Washington to the playoffs with 335 carries for 1,613 yards and 13 touchdowns and was honored as a finalist for the Pepsi MAX Rookie of the Year and FedEx Ground Player of the Year awards.
For the second year, the NFL's brightest current, former and future stars shined at the 2nd Annual National Football League Honors. Hollywood and NFL stars walked the red carpet at the Mahalia Jackson Theater before the signature event which honors the best players and performances during the 2012 season.
Morris took a few minutes to talk about his first Super Bowl experience, music and why he stays humble and focused.
What's it like for you to be in New Orleans to celebrate the Super Bowl?
Alfred Morris: It's great. It's going to bring a lot of revenue. Coming in off the plane and driving into the city you can still some of the damage from Katrina that's still around and it saddened me a little bit but once you get into the city it's so lively and what's been going on since then and all the help that's poured into the city. This event coming back here for the Super Bowl is great bringing all the revenue and boosting the locals and their businesses. I'm glad it's back here and I'm glad that it's my first Super Bowl.
What's the guilty pleasure song on your iPod?
Alfred Morris: Oh man [laughs]. I really don't listen to much music. I listen to Katy Perry "Wide Awake" a lot. Don't tell anybody that [laughs].
What famous woman are you hoping is watching you play on Sundays?
Alfred Morris: That's a tough one. Sanaa Lathan. I'm a huge fan.
Congratulations on a fantastic rookie season and thank you from all my friends who had you on their fantasy teams.
Alfred Morris: Thank you. Glad to help out.
You're one of three Redskins rookies on the ballots for NFL Honors, how do you feel about that?
Alfred Morris: That's kudos to the coaching staff, the "big wigs" I like to call them, Bruce Allen and everyone who makes decisions for the Redskins organization, including Mr. [Dan] Snyder. It speaks volumes about their decision-making and the way they're turning this program around.
What was the first big purchase you made after you signed your first NFL contract?
Alfred Morris: I didn't treat myself to anything, honestly. Just being here was treat enough. Signing my name on a contract was treat enough because it took a lot to get here. I took a road less traveled, it was tough, it was hard, I made a lot of sacrifices. But I'm starting to see the fruits of my labor and just to keep my dream alive and make it a reality is reward enough.


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