The incremental cost of switching from Option B to Option B+ for the prevention of mother-to-child transmission of HIV.

OBJECTIVE: To estimate the incremental cost over 5 years of a policy switch from the Option B to the Option B+ protocol for the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). METHODS: Data from cost studies and other published sources were used to determine the cost, per woman and per cohort (1000 breastfeeding and 1000 non-breastfeeding women), of switching from Option B (maternal triple antiretroviral [ARV] regimen during pregnancy and breastfeeding plus daily nevirapine for the infant for 6 weeks) to Option B+ (maternal triple ARV regimen initiated during pregnancy and continued for life). The variables used to model the different scenarios were maternal CD4+ T lymphocyte (CD4+ cell) count (350-500 versus > 500 cells/µl), rate of decline in CD4+ cells (average, rapid, slow), breastfeeding status (yes, no) and breastfeeding duration (12, 18 or 24 months). FINDINGS: For women with CD4+ cell counts of 350-500 cells/µl, the incremental cost per 1000 women was 157,345 United States dollars (US$) for breastfeeding women and US$ 92,813 for non-breastfeeding women. For women with CD4+ cell counts > 500 cells/µl, the incremental cost per 1000 women ranged from US$ 363,443 to US$ 484,591 for breastfeeding women and was US$ 605,739 for non-breastfeeding women. CONCLUSION: From a cost perspective, a policy switch from Option B to Option B+ is feasible in PMTCT programme settings where resources are currently being allocated to Option B.

Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries.

BACKGROUND: Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia. METHODS AND FINDINGS: We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community. CONCLUSIONS: HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed.

Maximizing the impact of HIV prevention efforts: interventions for couples.

Despite efforts to increase access to HIV testing and counseling services, population coverage remains low. As a result, many people in sub-Saharan Africa do not know their own HIV status or the status of their sex partner(s). Recent evidence, however, indicates that as many as half of HIV-positive individuals in ongoing sexual relationships have an HIV-negative partner and that a significant proportion of new HIV infections in generalized epidemics occur within serodiscordant couples. Integrating couples HIV testing and counseling (CHTC) into routine clinic- and community-based services can significantly increase the number of couples where the status of both partners is known. Offering couples a set of evidence-based interventions once their HIV status has been determined can significantly reduce HIV incidence within couples and if implemented with sufficient scale and coverage, potentially reduce population-level HIV incidence as well. This article describes these interventions and their potential benefits.

Universal voluntary HIV testing in antenatal care settings: a review of the contribution of provider-initiated testing & counselling.

OBJECTIVE: To assess the contribution of provider-initiated testing and counselling (PITC) to achieving universal testing of pregnant women and, from available data on components of PITC, assess whether PITC adoption adheres to pre-test information, post-test counselling procedures and linkage to treatment. METHODS: Systematic review of published literature. Findings were collated and data extracted on HIV testing uptake before and after the adoption of a PITC model. Data on pre- and post-test counselling uptake and linkage to anti-retrovirals, where available, were also extracted. RESULTS: Ten eligible studies were identified. Pre-intervention testing uptake ranged from 5.5% to 78.7%. Following PITC introduction, testing uptake increased by a range of 9.9% to 65.6%, with testing uptake ≥85% in eight studies. Where reported, pre-test information was provided to between 91.5% and 100% and post-test counselling to between 82% and 99.8% of pregnant women. Linkage to ARVs for prevention of mother to child transmission (PMTCT) was reported in five studies and ranged from 53.7% to 77.2%. Where reported, PITC was considered acceptable by ANC attendees. CONCLUSION: Our review provides evidence that the adoption of PITC within ANC can facilitate progress towards universal voluntary testing of pregnant women. This is necessary to increase the coverage of PMTCT services and facilitate access to treatment and prevention interventions. We found some evidence that PITC adoption does not undermine processes inherent to good conduct of testing, with high levels of pre-test information and post-test counselling, and two studies suggesting that PITC is acceptable to ANC attendees.

Prevalence and correlates of GB virus C infection in HIV-infected and HIV-uninfected pregnant women in Bangkok, Thailand.

GB virus C (GBV-C) is an apathogenic virus that has been shown to inhibit HIV replication. This study examined the prevalence and correlates of GBV-C infection and clearance in three cohorts of pregnant women in Thailand. The study population consisted of 1,719 (1,387 HIV-infected and 332 HIV-uninfected) women from three Bangkok perinatal HIV transmission studies. Stored blood was tested for GBV-C RNA, GBV-C antibody, and if RNA-positive, genotype. Risk factors associated with the prevalence of GBV-C infection (defined as presence of GBV-C RNA and/or antibody) and viral clearance (defined as presence of GBV-C antibody in the absence of RNA) among women with GBV-C infection were examined using multiple logistic regression. The prevalence of GBV-C infection was 33% among HIV-infected women and 15% among HIV-uninfected women. GBV-C infection was independently associated (AOR, 95% CI) with an increasing number of lifetime sexual partners (referent-1 partner, 2 partners [1.60, 1.22-2.08], 3-10 partners [1.92, 1.39-2.67], >10 partners [2.19, 1.33-3.62]); injection drug use (5.50, 2.12-14.2); and HIV infection (3.79, 2.58-5.59). Clearance of GBV-C RNA among women with evidence of GBV-C infection was independently associated with increasing age in years (referent <20, 20-29 [2.01, 1.06-3.79] and ≥30 [3.18, 1.53-6.60]), more than 10 lifetime sexual partners (3.05, 1.38-6.75), and HIV infection (0.29, 0.14-0.59). This study found that GBV-C infection is a common infection among Thai women and is associated with HIV infection and both sexual and parenteral risk behaviors.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.

What will it take to achieve virtual elimination of mother-to-child transmission of HIV? An assessment of current progress and future needs.

BACKGROUND: The number of HIV-positive pregnant women receiving antiretroviral drugs (ARVs) to prevent mother-to-child transmission (MTCT) of HIV has increased rapidly. OBJECTIVE: To estimate the reduction in new child HIV infections resulting from prevention of MTCT (PMTCT) over the past decade. To project the potential impact of implementing the new WHO PMTCT guidelines between 2010 and 2015 and consider the efforts required to virtually eliminate MTCT, defined as <5% transmission of HIV from mother to child, or 90% reduction of infections among young children by 2015. METHODS: Data from 25 countries with the largest numbers of HIV-positive pregnant women were used to create five scenarios to evaluate different PMTCT interventions. A demographic model, Spectrum, was used to estimate new child HIV infections as a measure of the impact of interventions. RESULTS: Between 2000 and 2009 there was a 24% reduction in the estimated annual number of new child infections in the 25 countries, of which about one-third occurred in 2009 alone. If these countries implement the new WHO PMTCT recommendations between 2010 and 2015, and provide more effective ARV prophylaxis or treatment to 90% of HIV-positive pregnant women, 1 million new child infections could be averted by 2015. Reducing HIV incidence in reproductive age women, eliminating the current unmet need for family planning and limiting the duration of breastfeeding to 12 months (with ARV prophylaxis) could avert an additional 264 000 infections, resulting in a total reduction of 79% of annual new child infections between 2009 and 2015, approaching but still missing the goal of virtual elimination of MTCT. DISCUSSION: To achieve virtual elimination of new child infections PMTCT programmes must achieve high coverage of more effective ARV interventions and safer infant feeding practices. In addition, a comprehensive approach including meeting unmet family planning needs and reducing new HIV infections among reproductive age women will be required.

Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries.

CONTEXT: Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. OBJECTIVE: To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. DESIGN, SETTING, AND PATIENTS: 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. MAIN OUTCOME MEASURE: 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). RESULTS: 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. CONCLUSION: 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.

Factors associated with low early uptake of a national program to prevent mother to child transmission of HIV (PMTCT): results of a survey of mothers and providers, Botswana, 2003.

In Francistown, Botswana, approximately 40% of pregnant women are HIV positive. PMTCT has been available since 1999, antiretroviral (ARV) therapy since 2001, and 95% of women have antenatal care (ANC) and deliver in hospital. However, in 2002, only 33% of ANC clients were tested for HIV, and not all women with HIV received services. In 2003, we conducted a survey of 504 pregnant and postpartum women to explore reasons for poor program uptake, and interviewed 82 health providers about PMTCT. Most women (95%) believed that all pregnant women should be tested for HIV. In multivariate analysis, factors associated with having an HIV test included being interviewed at an urban site, having a high PMTCT knowledge score, knowing someone receiving PMTCT or ARV therapy, and having a partner who had been tested for HIV. Neither fear of stigma nor resistance from partners were frequent reasons for refusing an HIV test. Providers of HIV services reported discomfort with their knowledge and skills, and 84% believed HIV testing should be routine. Ensuring adequate knowledge about HIV and PMTCT, creating systems whereby HIV-positive women receiving care can educate and support other women, and making HIV testing routine for pregnant women may improve the uptake of HIV testing.

Early diagnosis of human immunodeficiency virus in infants using polymerase chain reaction on dried blood spots in Botswana's national program for prevention of mother-to-child transmission.

BACKGROUND: Botswana has high antenatal human immunodeficiency virus (HIV) prevalence (33.4%). The public health system provides free services for prevention of mother to child transmission of HIV (PMTCT) and antiretroviral therapy, which can reduce vertical HIV transmission from 35% to <5%. Infant HIV diagnosis is challenging in resource-limited settings, and HIV prevalence among HIV-exposed infants in Botswana is unknown. Dried blood spot (DBS) polymerase chain reaction (PCR) provides a feasible method to assess PMTCT programs and identify HIV-infected children. METHODS: We trained staff in 15 clinics and a hospital to obtain DBS on HIV-exposed infants age 6 weeks to 17 months receiving routine care. Samples were sent to the national HIV reference laboratory. Roche Amplicor 1.5 DNA PCR testing was performed. RESULTS: Between June-December 2005, 1931 HIV-exposed infants age 6 weeks to 17 months were tested for HIV, of whom 136 (7.0%) were HIV infected. Among infants

Infection with hepatitis C virus among HIV-infected pregnant women in Thailand.

OBJECTIVE: The purpose of this study was to describe the epidemiology of coinfection with hepatitis C virus (HCV) and HIV among a cohort of pregnant Thai women. METHODS: Samples from 1771 pregnant women enrolled in three vertical transmission of HIV studies in Bangkok, Thailand, were tested for HCV. RESULTS: Among HIV-infected pregnant women, HCV seroprevelance was 3.8% and the active HCV infection rate was 3.0%. Among HIV-uninfected pregnant women, 0.3% were HCV-infected. Intravenous drug use by the woman was the factor most strongly associated with HCV seropositivity. Among 48 infants tested for HCV who were born to HIV/HCV coinfected women, two infants were HCV infected for an HCV transmission rate of 4.2% (95% 0.51-14.25%). CONCLUSIONS: HCV seroprevalence and perinatal transmission rates were low among this Thai cohort of HIV-infected pregnant women.

International recommendations on antiretroviral drugs for treatment of HIV-infected women and prevention of mother-to-child HIV transmission in resource-limited settings: 2006 update.

The World Health Organization recommends that countries adopt more effective antiretroviral regimens to increase the effectiveness of the prevention of mother-to-child human immunodeficiency virus (HIV) transmission programs. The 2006 guidelines recommend a tiered approach for the delivery of antiretroviral to pregnant women who are infected with HIV and include triple-drug antiretroviral treatment for those women who are eligible. Those women who are not eligible for antiretroviral treatment should receive a combination prophylaxis antiretroviral regimen, preferably zidovudine from 28 weeks of gestation; zidovudine, lamivudine, and a single dose of nevirapine during delivery; and zidovudine and lamivudine for 7 days after delivery to reduce the development of nevirapine resistance. Newborn infants should receive a single dose of nevirapine and 1-4 weeks of zidovudine, depending on the duration of the regimen received by the mother. Although steps are being taken to provide more effective regimens, the use of single-dose nevirapine alone should still be used in situations in which more effective regimens are not yet feasible or available. HIV transmission through breastfeeding remains a problem, and several interventions are under evaluation that include maternal and/or infant antiretroviral prophylaxis during breastfeeding.

Approaches for scaling up human immunodeficiency virus testing and counseling in prevention of mother-to-child human immunodeficiency virus transmission settings in resource-limited countries.

Prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT) programs have nearly eliminated mother-to-child transmission of HIV in developed countries, but progress in resource-limited countries has been slow. A key factor limiting the scale-up of PMTCT programs is lack of knowledge of HIV serostatus. Increasing the availability and acceptability of HIV testing and counseling services will encourage more women to learn their status, providing a gateway to PMTCT interventions. Key factors contributing to the scale-up of testing and counseling include a policy of provider-initiated testing and counseling with right to refuse (opt-out); group pretest counseling; rapid HIV testing; innovative staffing strategies; and community and male involvement. Integration of testing and counseling within the community and all maternal and child health settings are critical for scaling-up and for linking women and their families to care and treatment services. This paper will review best practices needed for expansion of testing and counseling in PMTCT settings in resource-limited countries.

Infant human immunodeficiency virus diagnosis in resource-limited settings: issues, technologies, and country experiences.

Diagnosing human immunodeficiency virus (HIV) infection in infants is difficult because maternal HIV antibodies cross the placenta, causing positive serologic tests in HIV-exposed infants for the first several months of life. Early definitive diagnosis of HIV requires virologic testing such as polymerase chain reaction (PCR), which is the diagnostic standard in resource-rich settings but has been too complex and expensive for widespread use in most countries with high HIV prevalence. Early PCR testing can help HIV-infected infants access treatment, provide psychosocial benefits for families of uninfected infants, and help programs for prevention of mother-to-child transmission of HIV monitor their effectiveness. HIV testing, including PCR, is increasingly available for infants in resource-limited settings, but there are many barriers and complex policy decisions that need to be addressed before universal early testing can become standard. This paper reviews challenges and progress in the field and suggests ways to facilitate early infant testing in resource-limited settings.

The Effect of a Continuous Quality Improvement Intervention on Retention-In-Care at 6 Months Postpartum in a PMTCT Program in Northern Nigeria: Results of a Cluster Randomized Controlled Study.

BACKGROUND: Retention in care is critical for improving HIV-infected maternal outcomes and reducing vertical transmission. Health systems' interventions such as continuous quality improvement (CQI) may support health services to address factors that affect the delivery of HIV-related care and thereby influence rates of retention-in-care. METHODOLOGY: We evaluated the effect of a CQI intervention on retention-in-care at 6 months postpartum of pregnant women and mothers living with HIV who had been started on lifelong antiretroviral treatment. Thirty-two health care facilities were randomized to either implement the intervention or not. We considered women fully retained in care when they attended the 6-month postpartum visit and did not miss any previous scheduled visit by more than 30 days. RESULTS: Five hundred eleven women living with HIV attending antenatal clinics at 26 facilities were included in the analysis. Median age at enrolment was 27 years and gestational age was 20 weeks. Seventy-one percent of women were seen at 6-month postpartum irrespective of missing any scheduled visit. However, 43% of women were fully retained at 6-month postpartum and did not miss any scheduled visit based on our stringent study definition of retention. There was no significant difference in retention at 6 months between the intervention and control arms [44% vs. 41%, relative risk: 1.08; 95% confidence interval (CI): 0.78 to 1.49]. Initiation of ARV prophylaxis among infants within 72 hours was not different by study arm (66.0% vs. 74.7%, relative risk = 0.95; 95% CI: 0.84 to 1.07) but rates of early infant testing at 4-6 weeks were higher in intervention sites (48.8% vs. 25.3%, adjusted relative risk: 1.76; 95% CI: 1.27 to 2.42). CONCLUSIONS: CQI as implemented in this study did not differ across study arms in the rates of retention. Several intervention design or implementation issues or other contextual constraints may explain the absence of effect.

Using Small Tests of Change to Improve PMTCT Services in Northern Nigeria: Experiences From Implementation of a Continuous Quality Improvement and Breakthrough Series Program.

BACKGROUND: Continuous Quality Improvement (CQI) is a process where health teams systematically collect and regularly reflect on local data to inform decisions and modify local practices and so improve delivery of services. We implemented a cluster randomized trial to examine the effects of CQI interventions on Prevention of Mother-to-Child Transmission (PMTCT) services. Here, we report our experiences and challenges establishing CQI in 2 high HIV prevalence states in northern Nigeria. METHODS: Facility-based teams were trained to implement CQI activities, including structured assessments, developing change packages, and participation in periodic collaborative learning sessions. Locally evolved solutions (change ideas) were tested and measured using process data and intermediate process indicators were agreed including overall time spent accessing services, client satisfaction, and quality of data. RESULTS: Health workers actively participated in clinic activities and in the collaborative learning sessions. During the study, the mean difference in time spent accessing services during clinic visits increased by 40 minutes (SD = 93.4) in the control arm and decreased by 44 minutes (SD = 73.7) in the intervention arm. No significant difference was recorded in the mean client satisfaction assessment score by study arm. The quality of data was assessed using a standardized tool scored out of 100; compared with baseline data, quality at the end of study had improved at intervention sites by 6 points (95% CI: 2.0 to 10.1). CONCLUSIONS: Health workers were receptive to CQI process. A compendium of "change ideas" compiled into a single change package can be used to improve health care delivery.

Time to first positive HIV-1 DNA PCR may differ with antiretroviral regimen in infants infected with non-B subtype HIV-1.

OBJECTIVE: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. DESIGN: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N = 405). METHODS: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. RESULTS: Maternal antiretroviral regimens included: no antiretrovirals (n = 138), single-nucleoside analog reverse transcriptase inhibitor (n = 165), single-dose nevirapine with zidovudine (n = 66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n = 36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P < 0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P = 0.04). CONCLUSION: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.

Should HIV testing for all pregnant women continue? Cost-effectiveness of universal antenatal testing compared to focused approaches across high to very low HIV prevalence settings.

INTRODUCTION: HIV testing is the entry point for the elimination of mother-to-child transmission of HIV. Decreasing external funding for the HIV response in some low- and middle-income countries has triggered the question of whether a focused approach to HIV testing targeting pregnant women in high-burden areas should be considered. This study aimed at determining and comparing the cost-effectiveness of universal and focused HIV testing approaches for pregnant women across high to very low HIV prevalence settings. METHODS: We conducted a modelling analysis on health and cost outcomes of HIV testing for pregnant women using four country-based case scenarios (Namibia, Kenya, Haiti and Viet Nam) to illustrate high, intermediate, low and very low HIV prevalence settings. We used subnational prevalence data to divide each country into high-, medium- and low-burden areas, and modelled different antenatal and testing coverage in each. RESULTS: When HIV testing services were only focused in high-burden areas within a country, mother-to-child transmission rates remained high ranging from 18 to 23%, resulting in a 25 to 69% increase in new paediatric HIV infections and increased future treatment costs for children. Universal HIV testing was found to be dominant (i.e. more QALYs gained with less cost) compared to focused approaches in the Namibia, Kenya and Haiti scenarios. The universal approach was also very cost-effective compared to focused approaches, with $ 125 per quality-adjusted life years gained in the Viet Nam-based scenario of very low HIV prevalence. Sensitivity analysis further supported the findings. CONCLUSIONS: Universal approach to antenatal HIV testing achieves the best health outcomes and is cost-saving or cost-effective in the long term across the range of HIV prevalence settings. It is further a prerequisite for quality maternal and child healthcare and for the elimination of mother-to-child transmission of HIV.