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.

First population-level effectiveness evaluation of a national programme to prevent HIV transmission from mother to child, South Africa.

BACKGROUND: There is a paucity of data on the national population-level effectiveness of preventing mother-to-child transmission (PMTCT) programmes in high-HIV-prevalence, resource-limited settings. We assessed national PMTCT impact in South Africa (SA), 2010. METHODS: A facility-based survey was conducted using a stratified multistage, cluster sampling design. A nationally representative sample of 10 178 infants aged 4-8 weeks was recruited from 565 clinics. Data collection included caregiver interviews, record reviews and infant dried blood spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine ≤10 weeks; 2b: incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information. Findings were adjusted for non-response, survey design and weighted for live-birth distributions. RESULTS: Nationally, 32% of live infants were HEI; early mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total 29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had missing ARV information (3b). Controlling for other factors groups, 1b and 2a had similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a, 1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to 18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to 5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively). CONCLUSIONS: SA, a high-HIV-prevalence middle income country achieved <5% MTCT by 4-8 weeks post partum. The long-term impact on PMTCT on HIV-free survival needs urgent assessment.

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.

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.

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.

Reduced mother-to-child transmission of HIV associated with infant but not maternal GB virus C infection.

BACKGROUND: Prolonged coinfection with GB virus C (GBV-C) has been associated with improved survival in human immunodeficiency virus (HIV)-infected adults. We investigated whether maternal or infant GBV-C infection was associated with mother-to-child transmission (MTCT) of HIV-1 infection. METHODS: The study population included 1364 HIV-infected pregnant women enrolled in 3 studies of MTCT of HIV in Bangkok, Thailand (the studies were conducted from 1992-1994, 1996-1997, and 1999-2004, respectively). We tested plasma collected from pregnant women at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If GBV-C RNA was detected in the maternal samples, the 4- or 6-month infant sample was tested for GBV-C RNA. The rates of MTCT of HIV among GBV-C-infected women and infants were compared with the rates among women and infants without GBV-C infection. RESULTS: The prevalence of GBV-C RNA in maternal samples was 19%. Of 245 women who were GBV-C RNA positive, 101 (41%) transmitted GBV-C to their infants. Of 101 infants who were GBV-C RNA positive, 2 (2%) were infected with HIV, compared with 162 (13%) of 1232 infants who were GBV-C RNA negative (odds ratio [OR] adjusted for study, 0.13 [95% confidence interval {CI}, 0.03-0.54]). This association remained after adjustment for maternal HIV viral load, receipt of antiretroviral prophylaxis, CD4(+) count, and other covariates. MTCT of HIV was not associated with the presence of GBV-C RNA (adjusted OR [aOR], 0.94 [95% CI, 0.62-1.42]) or GBV-C antibody (aOR, 0.90 [95% CI, 0.54-1.50]) in maternal samples. CONCLUSIONS: Reduced MTCT of HIV was significantly associated with infant acquisition of GBV-C but not with maternal GBV-C infection. The mechanism for this association remains unknown.

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

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.