Use of Service Data to Inform Pediatric HIV-free Survival Following Prevention of Mother-to-Child Transmission Programs in Rural Malawi

Abstract Background Recent years have seen rapid and significant progress in science and implementation of programs to prevent mother-to-child transmission of HIV. Programs that support PMTCT routinely monitor service provision but very few have measured their effectiveness. The objective of the study was to use service data to inform HIV-free survival among HIV exposed children that received antiretroviral drugs to prevent mother-to-child transmission (PMTCT) of HIV. The study was conducted in two rural districts in Malawi with support from FHI 360. Methods A descriptive observational study of PMTCT outcomes was conducted between June 2005 and June 2009. The dataset included patient-level data of all pregnant women 1) that tested HIV-positive, 2) that were dispensed with antiretroviral prophylaxis, and 3) whose addresses were available for home visits. The data were matched to each woman’s corresponding antenatal clinic data from home visit registers. Results Out of 438 children whose home addresses were available, 33 (8%) were lost to follow-up, 35 (8%) were alive but not tested for HIV by the time home visit was conducted, and 52 (12%) were confirmed deceased. A total of 318 children were alive at the time of the home visit and had an HIV antibody test done at median age 15 months. The resulting estimated 24-month probability of HIV-free survival over all children was 78%. Among children who did not receive nevirapine, the estimated 24-month probability of HIV-free survival was 61%, and among those who did receive NVP syrup the estimate was 82%. Conclusions When mothers and newborns received nevirapine, the estimated 24-month probability of HIV-free survival among children was high at 82% (CI: 54% to 99%). However this conclusion should be interpreted cautiously 1) due to the wide confidence interval; and 2) because the confidence interval range includes 55%, which is the natural HIV-free survival rate in the absence of a PMTCT intervention. This analysis highlighted the need of quality data and well-structured home visits to assess PMTCT effectiveness

Verification of chemistry reference ranges using a simple method in sub-Saharan Africa

Background: Chemistry safety assessments are interpreted by using chemistry reference ranges (CRRs). Verification of CRRs is time consuming and often requires a statistical background. Objectives: We report on an easy and cost-saving method to verify CRRs. Methods: Using a former method introduced by Sigma Diagnostics, three study sites in sub- Saharan Africa, Bondo, Kenya, and Pretoria and Bloemfontein, South Africa, verified the CRRs for hepatic and renal biochemistry assays performed during a clinical trial of HIV antiretroviral pre-exposure prophylaxis. The aspartate aminotransferase/alanine aminotransferase, creatinine and phosphorus results from 10 clinically-healthy participants at the screening visit were used. In the event the CRRs did not pass the verification, new CRRs had to be calculated based on 40 clinically-healthy participants. Results: Within a few weeks, the study sites accomplished verification of the CRRs without additional costs. The aspartate aminotransferase reference ranges for the Bondo, Kenya site and the alanine aminotransferase reference ranges for the Pretoria, South Africa site required adjustment. The phosphorus CRR passed verification and the creatinine CRR required adjustment at every site. The newly-established CRR intervals were narrower than the CRRs used previously at these study sites due to decreases in the upper limits of the reference ranges. As a result, more toxicities were detected. Conclusion: To ensure the safety of clinical trial participants, verification of CRRs should be standard practice in clinical trials conducted in settings where the CRR has not been validated for the local population. This verification method is simple, inexpensive, and can be performed by any medical laboratory

Prevention of mother-to-child transmission of HIV in Zambia: implementing efficacious ARV regimens in primary health centers

<p>Abstract</p> <p>Background</p> <p>Safety and effectiveness of efficacious antiretroviral (ARV) regimens beyond single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT) have been demonstrated in well-controlled clinical studies or in secondary- and tertiary-level facilities in developing countries. This paper reports on implementation of and factors associated with efficacious ARV regimens among HIV-positive pregnant women attending antenatal clinics in primary health centers (PHCs) in Zambia.</p> <p>Methods</p> <p>Blood sample taken for CD4 cell count, availability of CD4 count results, type of ARV prophylaxis for mothers, and additional PMTCT service data were collected for HIV-positive pregnant women and newborns who attended 60 PHCs between April 2007 and March 2008.</p> <p>Results</p> <p>Of 14,815 HIV-positive pregnant women registered in the 60 PHCs, 2,528 (17.1%) had their CD4 cells counted; of those, 1,680 (66.5%) had CD4 count results available at PHCs; of those, 796 (47.4%) had CD4 count ≤ 350 cells/mm³and thus were eligible for combination antiretroviral treatment (cART); and of those, 581 (73.0%) were initiated on cART. The proportion of HIV-positive pregnant women whose blood sample was collected for CD4 cell count was positively associated with (1) blood-draw for CD4 count occurring on the same day as determination of HIV-positive status; (2) CD4 results sent back to the health facilities within seven days; (3) facilities <it>without </it>providers trained to offer ART; and (4) urban location of PHC. Initiation of cART among HIV-positive pregnant women was associated with the PHC's capacity to provide care and antiretroviral treatment services. Overall, of the 14,815 HIV-positive pregnant women registered, 10,015 were initiated on any type of ARV regimen: 581 on cART, 3,041 on short course double ARV regimen, and 6,393 on sdNVP.</p> <p>Conclusion</p> <p>Efficacious ARV regimens beyond sdNVP can be implemented in resource-constrained PHCs. The majority (73.0%) of women identified eligible for ART were initiated on cART; however, a minority (11.3%) of HIV-positive pregnant women were assessed for CD4 count and had their test results available. Factors associated with implementation of more efficacious ARV regimens include timing of blood-draw for CD4 count and capacity to initiate cART onsite where PMTCT services were being offered.</p

Prediction of second neurological attack in patients with clinically isolated syndrome using support vector machines

The aim of this study is to predict the conversion from clinically isolated syndrome to clinically definite multiple sclerosis using support vector machines. The two groups of converters and non-converters are classified using features that were calculated from baseline data of 73 patients. The data consists of standard magnetic resonance images, binary lesion masks, and clinical and demographic information. 15 features were calculated and all combinations of them were iteratively tested for their predictive capacity using polynomial kernels and radial basis functions with leave-one-out cross-validation. The accuracy of this prediction is up to 86.4% with a sensitivity and specificity in the same range indicating that this is a feasible approach for the prediction of a second clinical attack in patients with clinically isolated syndromes, and that the chosen features are appropriate. The two features gender and location of onset lesions have been used in all feature combinations leading to a high accuracy suggesting that they are highly predictive. However, it is necessary to add supporting features to maximise the accuracy. © 2013 IEEE

Use of service data to inform pediatric HIV-free survival following prevention of mother-to-child transmission programs in rural Malawi

Abstract Background Recent years have seen rapid and significant progress in science and implementation of programs to prevent mother-to-child transmission of HIV. Programs that support PMTCT routinely monitor service provision but very few have measured their effectiveness. The objective of the study was to use service data to inform HIV-free survival among HIV exposed children that received antiretroviral drugs to prevent mother-to-child transmission (PMTCT) of HIV. The study was conducted in two rural districts in Malawi with support from FHI 360. Methods A descriptive observational study of PMTCT outcomes was conducted between June 2005 and June 2009. The dataset included patient-level data of all pregnant women 1) that tested HIV-positive, 2) that were dispensed with antiretroviral prophylaxis, and 3) whose addresses were available for home visits. The data were matched to each woman’s corresponding antenatal clinic data from home visit registers. Results Out of 438 children whose home addresses were available, 33 (8%) were lost to follow-up, 35 (8%) were alive but not tested for HIV by the time home visit was conducted, and 52 (12%) were confirmed deceased. A total of 318 children were alive at the time of the home visit and had an HIV antibody test done at median age 15 months. The resulting estimated 24-month probability of HIV-free survival over all children was 78%. Among children who did not receive nevirapine, the estimated 24-month probability of HIV-free survival was 61%, and among those who did receive NVP syrup the estimate was 82%. Conclusions When mothers and newborns received nevirapine, the estimated 24-month probability of HIV-free survival among children was high at 82% (CI: 54% to 99%). However this conclusion should be interpreted cautiously 1) due to the wide confidence interval; and 2) because the confidence interval range includes 55%, which is the natural HIV-free survival rate in the absence of a PMTCT intervention. This analysis highlighted the need of quality data and well-structured home visits to assess PMTCT effectiveness.</p

Preexposure prophylaxis for HIV infection among African women.

BACKGROUND: Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. METHODS: In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety. RESULTS: HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. CONCLUSIONS: Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.)

HIV Retesting of HIV-Negative Pregnant Women in the Context of Prevention of Mother-to-Child Transmission of HIV in Primary Health Centers in Rural Zambia: What Did We Learn?

Background: This observational study describes implementation of HIV retesting of HIV-negative women in prevention of mother-to-child transmission (PMTCT) services in Zambia. Methods: Uptake of retesting and PMTCT services were compared across age, parity, and weeks of gestation at the time of the first HIV test, antiretrovirals regime, and HIV early diagnosis results from infants born to HIV-positive mothers. Results: A total of 19 090 pregnant women were tested for HIV at their first antenatal visit, 16 838 tested HIV-negative and were offered retesting 3 months later: 11 339 (67.3%) were retested; of those, 55 (0.5%) were HIV positive. Uptake of the PMTCT package by women HIV positive at retest was not different but HIV-exposed infants born to women who retested HIV positive were infected at a higher rate (11.1%) compared to those born to women who tested HIV positive at their initial test (3.2%). Conclusion: We suggest rigorously (1) measuring the proportion of MTCT attributable to women who seroconvert during pregnancy and possibly adjust PMTCT approaches and (2) addressing the substantial loss to follow-up of HIV-negative pregnant women before HIV retesting

Mother and child characteristics.

<p>Mother and child characteristics.</p

Estimated Adjusted Odds Ratio and 95% Confidence Intervals for ARV exposures and non ARV-related parameters.

<p>Estimated Adjusted Odds Ratio and 95% Confidence Intervals for ARV exposures and non ARV-related parameters.</p