Nevirapine Coverage Research Articles

Performance of HIV Prevention of Mother-To-Child Transmission Programs in Sub-Saharan Africa: Longitudinal Assessment of 64 Nevirapine-Based Programs Implemented in 25 Countries, 2000-2011.

BackgroundTo evaluate the performance and to identify predictive factors of performance in prevention of mother-to-child HIV transmission programs (PMTCT) in sub-Saharan African countries.MethodsFrom 2000 to 2011, PMTCT programs included in the Viramune Donation Programme (VDP) were prospectively followed. Each institution included in the VDP provided data on program implementation, type of management institution, number of PMTCT sites, key programs outputs (HIV counseling and testing, NVP regimens received by mothers and newborns). Nevirapine Coverage Ratio (NCR), defined as the number of women who should have received nevirapine (observed HIV prevalence x number of women in antenatal care), was used to measure performance. Included programs were followed every six months through progress reports.ResultsA total of 64 programs in 25 sub-Saharan African countries were included. The mean program follow-up was 48.0 months (SD = 24.5); 20,084,490 women attended in antenatal clinics were included. The overall mean NCR was 0.52 (SD = 0.25), with an increase from 0.37 to 0.57 between the first and last progress reports (p<.0001); NCR increased by 3.26% per year-program. Between the first and the last report, the number of women counseled and tested increased from 64.3% to 86.0% (p<.0001), the number of women post-counseled from 87.5% to 91.3% (p = 0.08). After mixed linear regression analysis, type of responsible institution, number of women attended in ANC, and program initiation in 2005-2006 were significant predictive factors associated with the NCR. The effect of the time period increased from earlier to later periods.ConclusionA longitudinal assessment of large PMTCT programs shows that scaling-up of programs was increased in sub-Saharan African countries. The PMTCT coverage increased throughout the study period, especially after 2006. Performance may be better for programs with a small or medium number of women attended in ANC. Identification of factors that predict PMTCT program performance may help in the development and expansion of additional large PMTCT services in sub-Saharan Africa.

Scaling up prevention of mother-to-child HIV transmission programs in sub-Saharan African countries: a multilevel assessment of site-, program- and country-level determinants of performance

BackgroundUptake of prevention of mother-to-child HIV transmission (PMTCT) programs remains challenging in sub-Saharan Africa because of multiple barriers operating at the individual or health facility levels. Less is known regarding the influence of program-level and contextual determinants. In this study, we explored the multilevel factors associated with coverage in single-dose nevirapine PMTCT programs.MethodsWe analyzed aggregate routine data collected within the framework of the Viramune® Donation Programme (VDP) from 269 sites in 20 PMTCT programs and 15 sub-Saharan countries from 2002 to 2005. Site performance was measured using a nevirapine coverage ratio (NCR), defined as the reported number of women receiving nevirapine divided by the number of women who should have received nevirapine (observed HIV prevalence x number of women in antenatal care [ANC]). Data on program-level determinants were drawn from the initial application forms, and country-level determinants from the Demographic and Health Surveys (DHS) and the World Bank (World Development Indicators). Multilevel linear mixed models were used to identify independent factors associated with NCR at the site-, program- and country-level.ResultsOf 283,410 pregnant women attending ANC in the included sites, 174,312 women (61.5%) underwent HIV testing after receiving pre-test counselling, of whom 26,700 tested HIV positive (15.3%), and 22,591 were dispensed NVP (84.6%). Site performance was highly heterogeneous between and within programs. Mean NCR by site was 43.8% (interquartile range: 19.1-63.9). Multilevel analysis identified higher HIV prevalence (Beta coefficient: 25.1, 95% confidence interval [CI] 18.7 to 31.6), higher proportion of persons with knowledge of PMTCT (8.3; CI 0.5 to 16.0), higher health expenditure as a proportion of Gross Domestic Product (3.9 per %; CI 2.0 to 5.8) and lower percentage of rural population (-0.7 per %; CI -1.0 to -0.5) as significant country-level predictors of higher NCR at the p<0.05 level. A medium ANC monthly activity (30-100/month) was the only site-level predictor found (-7.6; CI -15.1 to -0.1).ConclusionsHeterogeneity of nevirapine coverage between sites and programs was high. Multilevel analysis identified several significant contextual determinants, which may warrant additional research to further define important multi-level and potentially modifiable determinants of performance of PMTCT programs.

Improved Detection of Incident HIV Infection and Uptake of PMTCT Services in Labor and Delivery in a High HIV Prevalence Setting

To maximize prevention of mother-to-child transmission of HIV (PMTCT) effectiveness and increase identification of HIV status in maternity units in Swaziland. With a quasi-experimental design, 3 maternity units were randomly assigned to the training intervention and 3 units were controls. Targeted on-site training was provided to nurse-midwives in intervention sites. HIV status was recorded with testing offered to women presenting with unknown and distant negative status. Cord blood was obtained and tested for HIV antibodies and presence of nevirapine as a marker of PMTCT intervention coverage. Contingency tables and χ² tests were used to test for associations between frequencies of events. Of the 2444 enrolled women, 215 (9%) arrived in maternity with unknown status and 1398 (58%) had tested HIV negative in antenatal clinic. Significantly more HIV-negative women (45%) and women with unknown status (96%) in intervention sites were tested compared with similar women in control sites, 14% and 65%, respectively (P < 0.0001 for both). Nevirapine coverage in HIV-positive cord blood was significantly higher in intervention sites (80%) than in control sites (69%, P < 0.0001). Cumulative HIV incidence was 4% with an incidence rate of 16.8 per 100 person-years. Antiretroviral prophylaxis coverage in seroconverters was significantly higher in intervention sites 54% (13 of 24) than the control group [26% (9 of 34), P = 0.03]. In high HIV prevalence settings, such as Swaziland, the incidence of HIV during pregnancy is high. An on-site training intervention for maternity nurses significantly increases the identification of HIV infection and maximizes the provision of PMTCT interventions.

Nevirapine for the Prevention of Mother-to-Child Transmission of HIV: A Nation-Wide Coverage Survey in Côte d'Ivoire

Single-dose nevirapine (NVP) is the simplest antiretroviral regimen for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. We evaluated NVP coverage among HIV-infected delivering women in Côte d'Ivoire. A cross-sectional survey of mother-infant pairs was conducted between November 2007 and September 2008 in 10 randomly selected facilities providing delivery services in the country. All sites used at least NVP for PMTCT. Anonymous HIV test and blood collection for NVP concentration measurement were performed in labor wards. NVP coverage was defined as the proportion of maternal and infant NVP intake confirmed by cord blood chromatography and direct observation. A total of 9953 deliveries were enrolled. Median maternal age was 25 years, and the median number of antenatal care (ANC) visits was 3. Of the 9747 women (97.9%) who made at least 1 ANC visit, 5880 (60.3%) received an HIV test proposal, 5135 (87.3%) accepted it, and 251 (4.9%) were diagnosed HIV infected; 176 of them (70.1%) received antiretroviral prophylaxis according to the medical record. Using anonymous cord blood surveillance, HIV prevalence was 5.9% (570 of 9646), maternal NVP coverage was 24.3% (138 of 570), and maternal and infant NVP coverage was 17.9% (102 of 570). In multivariate analysis, maternal NVP coverage was associated with 2-3 ANC visits [adjusted odds ratio (aOR): 2.61; 95% confidence interval (CI): 1.27 to 5.39] or ≥ 4 ANC visits (aOR: 3.84; 95% CI: 1.86 to 7.90) (ref. ≤ 1), and giving birth in clinic of first ANC visit (aOR: 2.21; 95% CI: 1.43 to 3.40). Maternal and infant NVP coverage was low irrespective of the method. Anonymous cord blood surveillance is more reliable for documenting PMTCT coverage.

Integrating prevention of mother-to-child HIV transmission (PMTCT) programmes with other health services for preventing HIV infection and improving HIV outcomes in developing countries

Every year nearly 400,000 children are infected with HIV through mother-to-child transmission (MTCT), which is responsible for more than 90% of HIV infections in children. In high-income countries, the MTCT rate is less than 1% through perinatal prevention of mother-to-child HIV transmission (PMTCT) interventions. In low- and middle-income countries, PMTCT programme coverage remains low and consequently transmission rate high. The World Health Organisation recommends integration of PMTCT programmes with other healthcare services to increase access and improve uptake of these interventions. To assess the effect of integration of perinatal PMTCT measures with other health care services on coverage and service uptake compared to stand-alone PMTCT programmes and healthcare services or partially integrated PMTCT interventions. We searched the following databases, for the time period of January 1990 to August 2010: MEDLINE, EMBASE, the WHO Global Health Library, CAB abstracts, CINAHL, POPLINE, PsycINFO, Sociological Abstracts, ERIC, AEGIS, Google Scholar, New York Academy of Medicine Grey Literature, Open SIGLE, British Library Catalogue, ProQuest Dissertation & Theses Database and U.S. National Library of Medicine Gateway system. We also searched the Cochrane Database of Systematic Reviews (the Cochrane Library 2010, Issue 7), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2010, Issue 7), Database of Abstracts of Reviews on Effects (the Cochrane Library 2010, Issue 7). We also searched for ongoing trials in the WHO International Clinical Trials Registry and Controlled clinical trials (January 1990 to July 2010). We performed ISI Web of Knowledge Cited Reference Search and scanned the reference lists of the included articles for additional relevant studies. We contacted authors to locate additional eligible studies. To maximise sensitivity we did not employ any methodological filters. Randomised controlled trials (RCT), cluster-randomised controlled trials (cluster RCT), controlled clinical trials (CCT), controlled before and after (CBA) studies and interrupted time series (ITS) studies comparing integrated PMTCT interventions to non-integrated or partially integrated care for pregnant women, mothers and their infants in low- and middle-income countries. Two review authors independently ran the searches, selected studies, assessed methodological quality, and extracted data. The third review author resolved any disagreements. Only one study met the inclusion criteria. A cluster-randomised trial (12 clusters, n=7664), compared mother-infant nevirapine coverage at labour ward between intervention clinics implementing rapid HIV testing with structured nevirapine assessment and control clinicsimplementing informal assessment of nevirapine adherence. The authors measured nevirapine coverage in all clinics at baseline and after the implementation of the intervention. An increase of 10% (range of difference in coverage from -10% to +33%) was observed in the intervention sites compared to 10% decline in mother-infant coverage in the control sites (range of difference in coverage from -13% to 0%). The study showed that the probability of nevirapine coverage of mothers and their infants in the intervention arm compared to control arm increased from 0.89 at baseline to 1.22 during the intervention period, representing a multiplicative effect of 1.37 upon the ratio of relative risks at baseline (RR 1.37, bootstrapped 95% CI, 1.041.77). The study had a low risk of bias. No studies were found that evaluated the effectiveness of integrating other perinatal PMTCT interventions with healthcare services. We found only one study suggesting that integrating perinatal PMTCT interventions with other healthcare services in low- and middle-income countries increases the proportion of pregnant women, mothers and infants receiving PMTCT intervention. The weak evidence base does not enable making any inferences for other countries or contexts. The study that met the inclusion criteria assessed only the impact of integrating PMTCT intervention in labour ward on the proportion of mothers and their infants receiving nevirapine. The study showed significant improvement in intervention coverage but it onlyaddressed the labour ward aspect of PMTCT programme. We did not find sufficient evidence to make definitive conclusions about the effectiveness of integration of these interventions with other health services rather than providing them as stand-alone services. Further research is urgently needed to assess the effect of integrating perinatal prevention of mother-to-child HIV transmission interventions with other health services on intervention coverage, service uptake, quality of care and health outcomes and the optimal integration modality.

Coverage of Nevirapine-Based Services to Prevent Mother-to-Child HIV Transmission in 4 African Countries

Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. Cross-sectional surveillance study of mother-infant pairs using umbilical cord blood samples collected between June 10, 2007, and October 30, 2008, from 43 randomly selected facilities (grouped as 25 service clusters) providing delivery services in Cameroon, Côte d'Ivoire, South Africa, and Zambia. All sites used at least single-dose nevirapine to prevent mother-to-child HIV transmission and some sites used additional prophylaxis drugs. Population nevirapine coverage, defined as the proportion of HIV-exposed infants in the sample with both maternal nevirapine ingestion (confirmed by cord blood chromatography) and infant nevirapine ingestion (confirmed by direct observation). A total of 27,893 cord blood specimens were tested, of which 3324 were HIV seropositive (12%). Complete data for cord blood nevirapine results were available on 3196 HIV-seropositive mother-infant pairs. Nevirapine coverage varied significantly by site (range: 0%-82%). Adjusted for country, the overall coverage estimate was 51% (95% confidence interval [CI], 49%-53%). In multivariable analysis, failed coverage of nevirapine-based services was significantly associated with maternal age younger than 20 years (adjusted odds ratio [AOR], 1.44; 95% CI, 1.18-1.76) and maternal age between 20 and 25 years (AOR, 1.28; 95% CI, 1.07-1.54) vs maternal age of older than 30 years; 1 or fewer antenatal care visits (AOR, 2.91; 95% CI, 2.40-3.54), 2 or 3 antenatal care visits (AOR, 1.93; 95% CI, 1.60-2.33), and 4 or 5 antenatal care visits (AOR, 1.56; 95% CI, 1.34-1.80) vs 6 or more antenatal care visits; vaginal delivery (AOR, 1.22; 95% CI, 1.03-1.44) vs cesarean delivery; and infant birth weight of less than 2500 g (AOR, 1.34; 95% CI, 1.11-1.62) vs birth weight of 3500 g or greater. In this random sampling of sites with services to prevent mother-to-child HIV transmission, only 51% of HIV-exposed infants received the minimal regimen of single-dose nevirapine.

Utilization of therapeutic intervention to prevent mother to child transmission of HIV in a teaching hospital in Kolkata, India

To assess the uptake of an HIV screening program and therapeutic intervention to minimize the risk of mother to child transmission. This was a cross-sectional, observational study with retrospective data obtained from patient medical records. Pregnant women presenting to a tertiary care center in Kolkata, India, from 1 January 2004 - 31 December 2007 underwent HIV serology by rapid test after receiving group counseling. Care was administered using a standard national protocol by a multi-disciplinary team of health-care personnel. Main outcome measures were: acceptance of pretest counseling and HIV testing by pregnant women attending antenatal clinic services, post-test counseling rate, coverage rate of nevirapine to mother-child pairs, and averted HIV infection in children. Of the 52 127 new antenatal booking visits, 49 580 (95.11%) women attended pretest counseling and 47 506 (91.13%) women accepted HIV testing. Eighty-six women were found to be seropositive. The seroprevalence rate of HIV infection was 0.17%. Thirty-seven mothers (88%) and all newborn infants (100%) had received nevirapine prophylaxis. Overall nevirapine coverage rate was 48%. Twenty-four of the mother-infant pairs that we assessed had infants who were aged over 18 months by June 2008. Eleven (45.83%) of these women turned up with their babies for a blood test at 18 months. Three (27.27%) babies tested reactive. As uptake of testing is high and detection of HIV-infected women in pregnancy remains very low, a radical rethinking of policies on therapeutic intervention and their implementation now needs to be undertaken.

A cluster-randomized trial of enhanced labor ward-based PMTCT services to increase nevirapine coverage in Lusaka, Zambia.

Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV (PMTCT) would improve nevirapine (NVP) coverage. Cluster-randomized trial at 12 public-sector delivery centers in Lusaka, Zambia. Following a baseline surveillance period, 12 labor wards were randomized, six to offer opt-in HIV testing to women of unknown serostatus (with NVP administration as indicated) and to assess NVP adherence among known HIV-infected women. The six control labor wards provided the standard of care. The NVP coverage endpoint was defined as the proportion of HIV-infected/exposed women/infant pairs with confirmed NVP ingestion. We used generalized estimating equations (GEE) to determine the odds of coverage associated with the intervention and ultimately used the parameters for the estimated GEE model to estimate relative risk. Between October 2005 and January 2006, 7664 women gave birth at participating clinics. We collected anonymous-linked blood from 7592 (99%) umbilical cords; tested 7438 (97%) for HIV, 1618 (22%) were seropositive, and of these, 1279 (79%) were tested for NVP. At baseline (preintervention), the probability of HIV-infected/exposed women/infant pairs receiving NVP in treatment clinics (42%) was 0.89 times the probability of being covered in control clinics (53%) whereas during the intervention period the probability of treatment clinic coverage (52%) was 1.22 the probability control clinic coverage (43%), representing a multiplicative effect of 1.37 upon the RR at baseline (ratio of relative risks 1.37, bootstrapped 95% CI, 1.04-1.77). Labor ward-based PMTCT programs are feasible and can have a significant, positive impact on NVP coverage.

Reducing vertical HIV transmission in Kinshasa, Democratic Republic of Congo: trends in HIV prevalence and service delivery

Scale-up of vertical HIV transmission prevention has been too slow in sub-Saharan Africa. We describe approaches, challenges, and results obtained in Kinshasa. Staff members of 21 clinics managed by public servants or non-governmental organizations were trained in improved basic antenatal care (ANC) including nevirapine (NVP)-based HIV transmission prevention. Program initiation was supported on-site logistically and technically. Aggregate implementation data were collected and used for program monitoring. Contextual information was obtained through a survey. Among 45,262 women seeking ANC from June 2003 through July 2005, 90% accepted testing; 792 (1.9%) had HIV of whom 599 (76%) returned for their result. Among 414 HIV+ women who delivered in participating maternities, NVP coverage was 79%; 92% of newborns received NVP. Differences were noted by clinic management in program implementation and HIV prevalence (1.2 to 3.0%). Initiating vertical HIV transmission prevention embedded in improved antenatal services in a fragile, fragmented, severely resource-deprived health care system was possible and improved over time. Scope and quality of service coverage should further increase; strategies to decrease loss to follow-up of HIV+ women should be identified to improve program effectiveness. The observed differences in HIV prevalence highlight the importance of selecting representative sentinel surveillance centers.

Field Performance of a Thin-Layer Chromatography Assay for Detection of Nevirapine in Umbilical Cord Blood

Purpose: Although cord blood surveillance can measure the effectiveness of nevirapine (NVP)-based programs for the prevention of mother-to-child HIV transmission (PMTCT), it requires the ability to detect nevirapine in plasma. At present, the only validated method is high-performance liquid chromatography (HPLC), a technique poorly suited for most resource-constrained settings. Method: We evaluated the field performance for a simple and inexpensive thin-layer chromatography (TLC) assay for NVP detection. We developed a conditional probability model to compare 2 testing algorithms: HPLC alone, and TLC screening followed by HPLC confirmation of negative results. Results: When compared to HPLC, sensitivity of TLC was 0.67 (95% confidence interval [CI] 0.49–0.84) and specificity was 0.84 (95% CI 0.69–0.95). In this sample — where overall NVP coverage was 49% — positive predictive value was 0.80 and negative predictive value was 0.72. At baseline with population NVP coverage of 33%, cost per specimen was lower in the TLC-HPLC testing algorithm ($40 vs. $50), and the proportion of false results was acceptable (11%). As population NVP coverage increased, cost-efficiency improved and error rate dropped substantially. Conclusion: TLC is reasonably sensitive and specific for NVP detection. A 2-step testing algorithm incorporating TLC and HPLC provides cost-efficiency at little expense to test performance.

Field Performance of a Thin-Layer Chromatography Assay for Detection of Nevirapine in Umbilical Cord Blood

Purpose: Although cord blood surveillance can measure the effectiveness of nevirapine (NVP)-based programs for the prevention of mother-to-child HIV transmission (PMTCT), it requires the ability to detect nevirapine in plasma. At present, the only validated method is high-performance liquid chromatography (HPLC), a technique poorly suited for most resource-constrained settings. Method: We evaluated the field performance for a simple and inexpensive thin-layer chromatography (TLC) assay for NVP detection. We developed a conditional probability model to compare 2 testing algorithms: HPLC alone, and TLC screening followed by HPLC confirmation of negative results. Results: When compared to HPLC, sensitivity of TLC was 0.67 (95% confidence interval [CI] 0.49–0.84) and specificity was 0.84 (95% CI 0.69–0.95). In this sample — where overall NVP coverage was 49% — positive predictive value was 0.80 and negative predictive value was 0.72. At baseline with population NVP coverage of 33%, cost per specimen was lower in the TLC-HPLC testing algorithm ($40 vs. $50), and the proportion of false results was acceptable (11%). As population NVP coverage increased, cost-efficiency improved and error rate dropped substantially. Conclusion: TLC is reasonably sensitive and specific for NVP detection. A 2-step testing algorithm incorporating TLC and HPLC provides cost-efficiency at little expense to test performance.

Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia

To determine the population effectiveness of a city-wide perinatal HIV prevention program. An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP). All 10 public-sector delivery centers in Lusaka, Zambia participated. All mother-infant pairs delivering during the 12-week surveillance period at the participating centers and who received antenatal care at a public-sector facility in Lusaka were included in the study. The main outcome measure was population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the population that ingested NVP. Of 8787 women in the surveillance population, 7204 (82%) had been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers (90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother-infant pairs in the surveillance population received both a maternal and infant dose of NVP. Successful perinatal HIV prevention requires each mother-infant pair to negotiate a cascade of events that begins with offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance demonstrates that failures occur at each step, resulting in reduced coverage and diminished program effectiveness.

Universal nevirapine upon presentation in labor to prevent mother-to-child HIV transmission in high prevalence settings.

To assess the uptake of and adherence to nevirapine to prevent mother-to-child HIV transmission among women of unknown HIV serostatus presenting in labor. We also assessed preliminary efficacy of the approach. Women of unknown HIV serostatus presenting in labor were offered single-dose nevirapine in a prospective cohort study. Two additional contemporaneous comparison populations were also studied. We measured uptake by counting the number of women that accepted enrollment when offered. We measured adherence with cord blood nevirapine assay. We measured preliminary efficacy with HIV DNA polymerase chain reaction of infant blood spots at 4-6 weeks of life. Of 1591 women approached in labor, 634 (40%) took up the intervention and received nevirapine, of whom 185 (29%) were HIV infected. Of 179 cord blood specimens from HIV-exposed infants that could be evaluated, 178 (99.4%) had nevirapine detected. This was higher than the 73 of 98 (74%) adherence rate observed in a comparison cohort in which women self-administered nevirapine before presenting to the labor ward (P < 0.001). Of 145 available infant specimens, 17 (11.7%) showed evidence of infection at 4-6 weeks, compared with 12 of 60 (20%) infants born immediately prior to study commencement whose HIV-infected mothers did not receive nevirapine (P < 0.05). Nevirapine without HIV testing upon presentation in labor was accepted by two-fifths of women. Because therapy is directly observed, adherence is nearly perfect. Labor ward dosing to enhance nevirapine coverage should be considered as an adjunct to antenatal nevirapine administration for prevention of mother-to-child transmission of HIV.