Prevention of mother-to-child transmission of HIV--what next?

Mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) is a global problem. HIV can be transmitted from mother-to-child at various stages of pregnancy including in utero, intrapartum and during breastfeeding. A number of interventions have, therefore, been aimed at effectively providing alternatives to breastfeeding and limiting the risk of newborn infection during delivery, by using caesarian section as the mode of delivery and administering antiretroviral (ARV) drugs prepartum and peripartum. However, these approaches are not always possible in developing countries and the use of ARV drugs, in particular nevirapine, zidovudine and zidovudine/lamivudine, have been investigated in both developing countries and developed countries. The studies have involved the administration of various ARV prophylaxis regimens to HIV-infected pregnant women perinatally, either as monotherapy or in various combinations. In some studies, infants have also received ARV prophylaxis. Although studies have enrolled different populations and utilized various ARV drugs and regimens, encouraging reductions in the MTCT rates have been reported. These interventions have raised concerns regarding the development of ARV-resistant HIV strains. Mutations that confer resistance to nevirapine have been detected in pregnant women who received this drug, but the emergence of these mutations was not associated with an increased risk of transmission of HIV-1 to their infants. Studies are ongoing to determine if the presence of these mutations has implications for the subsequent administration of nevirapine, either to prevent MTCT of HIV-1 or for the mother's own health. Effective interventions that can reduce MTCT of HIV are now available worldwide. However, a number of issues remain to be resolved, particularly methods to reduce the transmission of the virus during breastfeeding and to deliver effective treatment for the mothers' own HIV infection.     

Parent to child transmission of HIV: policy considerations in the Asia-Pacific region.

BACKGROUND: As HIV spreads through many countries in Asia and the Pacific, women of reproductive age are becoming infected and we can expect increasing numbers of infants to be infected. Rapid advances in knowledge about mother to child transmission (MTCT), new findings from intervention studies, recognition of complex ethical implications, and changing attitudes and behaviours combine to create uncertainty for policy makers. OBJECTIVE: Policy makers need sound advice but MTCT and its prevention are complicated topics. We aim to provide an overview of MTCT of HIV and suggest some key points to consider in the allocation of resources. STUDY DESIGN: This is a policy analysis based on review of the literature, consultation with policy makers and researchers, and observations in the context of projects in developing countries. RESULTS: The risk of MTCT is between 15 and 40%, but the use of antiretroviral prophylaxis, elective caesarean section, and replacement of breastfeeding can reduce this to less than 4%. But most infected women in developing countries are unaware that they are HIV-infected and do not yet have access to these 'test-dependent' interventions (interventions based on testing for HIV infection). Population-based strategies that address known influences on the risk of MTCT can be implemented with benefits for the health of both men and women. The test-dependent interventions can have adverse effects as well as benefits, careful preparation is necessary before they are introduced in resource poor settings. The public health impact of test-dependent interventions is limited by difficulties in achieving wide coverage and because they miss women who become infected late in pregnancy or during lactation who have the highest risk of MTCT. CONCLUSIONS: We argue for a broad response to the problems raised by MTCT of HIV that includes gathering information to inform the introduction of strategies that do not depend on testing for HIV infection as well as the test-dependent interventions, community education that reaches men as well as women; strengthening of reproductive health services; and mobilising communities to care for infected women, their families, and orphans.     

Trends in antiretroviral therapy use and survival rates for a large cohort of HIV-infected children and adolescents in the United States, 1989-2001

BACKGROUND: In the United States, HIV-infected children and adolescents are aging and using antiretroviral (ARV) therapy for extended periods of time. OBJECTIVE: To assess trends in ARV use and long-term survival in an observational cohort of HIV-infected children and adolescents in the United States. METHODS: The Pediatric Spectrum of HIV Disease Study (PSD) is a prospective chart review of more than 2000 HIV-infected children and adolescents. Patients were included in the analysis from enrollment until last follow-up. RESULTS: Triple-ARV therapy use (for 6 months or more) increased from 27% to 66% during 1997 to 2001 (P < 0.0001, chi for trend). The proportion of patients receiving 3 or more sequential triple-therapy regimens also increased from 4% to 17% during 1997 to 2001 (P < 0.0001, chi for trend), however, and the durability of triple-therapy regimens decreased from 13 to 7 months from the first to third regimen. Survival rates for the 1997 to 2001 birth cohorts were significantly better than for the 1989 to 1993 and 1994 to 1996 cohorts (P < 0.0001). CONCLUSIONS: Survival rates in the PSD cohort have increased in association with triple-ARV therapy use. With continued changes in ARV regimens, effective modifications in ARV therapy and the sustainability of gains in survival need to be determined.     

Effectiveness of nevirapine and zidovudine in a pilot program for the prevention of mother-to-child transmission of HIV-1 in Uganda

Background

Single dose nevirapine and a short course of zidovudine (AZT) are now administered in most hospitals in Uganda to prevent mother-to-child transmission (MTCT) of HIV. The effectiveness of these antiretroviral (ARV) regimens has been shown in the clinical trials but has not been demonstrated outside the clinical trials setting in this country.

Objectives

The study evaluated the effectiveness of short course ARV regimens in a pilot program to prevent mother-to-child transmission of HIV and determined the risk factors for perinatal transmission.

Methods

Cross-sectional study design was used to compare perinatal transmission rates of HIV in two sets of mothers: ARV-treated mothers and ARV-untreated mothers.

Results

109 treated and 90 naïve mother-infant pairs were recruited. HIV transmission rates were similar in the nevirapine (10/61) and AZT (8/48) groups (16.4% vs. 16.7%) respectively but higher in the naïve group (43/90 48%, p= 0.0001). ARV therapy offers a protective effect against MTCT of HIV (Adjusted Odds Ratio 0.22 95%CI 0.09, 0.54) but mothers in Stage 1 and 2 of disease were more likely to benefit from this intervention than mothers in Stage 3 and 4.

Conclusion

In this community-based observational study, ARV reduces the risk of perinatal transmission of HIV but does not eliminate the risk completely. Early screening of asymptomatic pregnant women will identify a group of mothers more likely to benefit from the intervention.     

Low utilization of HIV testing during pregnancy: What are the barriers to HIV testing for women in rural India?

INTRODUCTION: Sixty percent of India's HIV cases occur in rural residents. Despite government policy to expand antenatal HIV screening and prevention of maternal-to-child transmission (PMTCT), little is known about HIV testing among rural women during pregnancy. METHODS: Between January and March 2006, a cross-sectional sample of 400 recently pregnant women from rural Maharashtra was administered a questionnaire regarding HIV awareness, risk, and history of antenatal HIV testing. RESULTS: Thirteen women (3.3%) reported receiving antenatal HIV testing. Neither antenatal care utilization nor history of sexually transmitted infection (STI) symptoms influenced odds of receiving HIV testing. Women who did not receive HIV testing, compared with women who did, were 95% less likely to have received antenatal HIV counseling (odds ratio = 0.05, 95% confidence interval: 0.02 to 0.17) and 80% less aware of an existing HIV testing facility (odds ratio = 0.19, 95% confidence interval: 0.04 to 0.75). CONCLUSIONS: Despite measurable HIV prevalence, high antenatal care utilization, and STI symptom history, recently pregnant rural Indian women report low HIV testing. Barriers to HIV testing during pregnancy include lack of discussion by antenatal care providers and lack of awareness of existing testing services. Provider-initiated HIV counseling and testing during pregnancy would optimize HIV prevention for women throughout rural India.     

Clinical and immunologic characteristics and therapeutic interventions in children born to human immunodeficiency virus-infected mothers in southern Taiwan.

Since the late 1990s, the epidemic of human immunodeficiency virus (HIV) infection in Taiwan has expanded dramatically. Pediatric HIV infection has also increased at an alarming pace. Nearly 40% of the HIV-infected children (<10 years) contracted infection through mother-to-child transmission (MTCT). The aims of this study were to evaluate the effects of interventions to prevent MTCT of HIV infection, and to describe the clinical and immunologic characteristics of children born to HIV-seropositive mothers in southern Taiwan. From 1995 to 2003, an observational, longitudinal study of 8 children born to HIV-infected mothers was carried out at a tertiary care university hospital. The median age at enrollment was 0.4 years (range, 1 day-7.5 years), and the mean duration of follow-up was 2.7 years. Four mothers were immigrants from southeastern Asia. Due to antenatal diagnosis of maternal HIV infection, 3 children underwent interventions, including cesarean section, prophylactic use of zidovudine, and bottle-feeding in order to prevent vertical transmission. Five children were born without interventions because of delayed diagnosis of maternal HIV infection. During follow-up, 2 children were found to be HIV-infected and 6 were not infected. The rate of MTCT was lower among patients with interventions (0% vs 40%). In HIV-exposed/non-infected children, the clinical and immunologic assessments were normal during follow-up. Both HIV-infected children progressed to the stage of acquired immunodeficiency syndrome. Early identification of HIV-seropositive pregnant women, implementations to reduce vertical transmission, and introduction of antiretroviral therapy permit optimism in the prevention and treatment of pediatric HIV infection.     

河南省HIV母婴传播的影响因素分析

目的 了解河南省HIV母婴传播情况,分析HIV母婴传播的危险和保护因素.方法 通过国家预防艾滋病母婴传播信息管理系统,收集2002-2013年HIV感染孕产妇及所分娩婴幼儿的有关干预信息,包括孕产妇HIV检测咨询、围产期保健服务、抗病毒药物阻断、婴幼儿随访检测等情况,采用非条件logistic回归对HIV母婴传播的影响因素进行分析.结果 截至2013年12月底,共有1 384例婴幼儿存活至18月龄,检测阳性婴幼儿60人,检测阴性婴幼儿l 324人.存活婴幼儿累计母婴传播率4.34％,存活婴幼儿分年度母婴传播率无明显降低趋势(X2=2.82,P=0.093).产妇孕早期接受预防HIV母婴传播服务(0R=0.22,95％ C.I.0.06～0.77),产妇及婴幼儿进行抗病毒药物阻断(0R=0.46,95％C.I.0.21～0.91),婴幼儿采取人工喂养(OR=0.08,95％ C.I.0.02～0.30)是HIV母婴传播的保护因素,产妇分娩过程采取侧切操作(0R=3.17,95％ C.I.1.37～7.36)是其危险因素.结论 河南省存活婴幼儿HIV母婴传播率较高,应针对主要影响因素一步完善预防HIV母婴传播的综合干预措施.     

Safety and efficacy of initiating highly active antiretroviral therapy in an integrated antenatal and HIV clinic in Johannesburg, South Africa

OBJECTIVE: To describe the safety and efficacy of highly active antiretroviral therapy (HAART) in pregnant women treated in an integrated antiretroviral antenatal clinic (ANC ARV). METHODS: A retrospective analysis was performed on patients attending the ANC ARV from August 2004 through February 2007. RESULTS: Data were collected on 689 treatment-naive pregnant women initiated on HAART. The mean age was 29.2 years. The mean baseline CD4 count was 154 cells per microliter, and mean baseline HIV viral load was 101,561 copies per milliliter. Tuberculosis was the most prevalent presenting opportunistic infection (7.7%). Stavudine, lamivudine, and nevirapine were initiated in 82% of women with the most frequent adverse drug reaction being nevirapine-associated skin rash (3.5%). Mean gestational age at HAART initiation was 27 weeks. Among women with follow-up data, 80% gained 50 or more CD4 cells per microliter and 80.5% achieved viral suppression to <1,000 copies per milliliter. Of 302 mother-infant pairs who completed postnatal follow-up, the HIV transmission rate was 5%. In women who received more than 7 weeks of HAART during pregnancy, transmission was 0.3%. CONCLUSIONS: Within the ANC ARV program, initiating pregnant women on HAART was feasible, safe, and effective. Advanced gestational age at treatment initiation and loss to follow-up emerge as important challenges in this population.     

Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra Study

OBJECTIVE: To investigate the possibility of reducing mother-to-child transmission (MTCT) of HIV-1 through breast-feeding by prophylactic antiretroviral (ARV) treatment of the infant during the breast-feeding period. DESIGN: An open-label, nonrandomized, prospective cohort study in Tanzania (Mitra). METHODS: HIV-1-infected pregnant women were treated according to regimen A of the Petra trial with zidovudine (ZDV) and lamivudine (3TC) from week 36 to 1 week postpartum. Infants were treated with ZDV and 3TC from birth to 1 week of age (Petra arm A) and then with 3TC alone during breast-feeding (maximum of 6 months). Counseling emphasized exclusive breast-feeding. HIV transmission was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breast-feeding population in arm A of the Petra trial, taking CD4 cell count and other possible confounders into consideration. RESULTS: There were 398 infants included in the transmission analysis in the Mitra study. The estimated cumulative proportion of HIV-1-infected infants was 3.8% (95% confidence interval [CI]: 2.0 to 5.6) at week 6 after delivery and 4.9% (95% CI: 2.7 to 7.1) at month 6. The median time of breast-feeding was 18 weeks. High viral load and a low CD4 T-cell count at enrollment were associated with transmission. The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2% (95% CI: 0.0 to 2.4). The cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI: 5.7 to 11.4). No serious adverse events related to the ARV treatment of infants occurred. The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50% lower than in the breast-feeding population of Petra arm A (relative hazard=2.61; P=0.001; adjusted values). The difference in transmission up to 6 months was significant also in the subpopulation of mothers with CD4 counts>or=200 cells/microL. CONCLUSIONS: The rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery are among the lowest reported in a breast-feeding population in sub-Saharan Africa. Prophylactic 3TC treatment of infants to prevent MTCT of HIV during breast-feeding was well tolerated by the infants and could be a useful strategy to prevent breast milk transmission of HIV when mothers do not need ARV treatment for their own health.     

Relationship between antiretroviral prescribing patterns and treatment guidelines in treatment-naive HIV-1-infected US veterans (1992-2004)

OBJECTIVE: To analyze temporal patterns of antiretroviral (ARV) prescribing practices relative to nationally defined guidelines in treatment-naive patients with HIV-1 infection. DESIGN: Retrospective cohort study. METHODS: We evaluated ARV prescribing patterns among ARV treatment-naive veterans who were receiving care within the US Department of Veterans Affairs (VA) from 1992 through 2004 in comparison to evolving adult HIV-1 treatment guidelines. RESULTS: A total of 15,934 patients initiated ARV treatment. Since 1999, >94% of patients initiated at least a 3-ARV medication combination, although the percentage of patients who initiated a guideline "preferred" or "alternative" regimen never rose to greater than 72% and was significantly associated with being black and with region of care. After 1999, 20% of patients started 4 or more active ARV agents in combination, which was significantly associated with lower baseline CD4 cell count, higher viral load, and receiving care in the western United States. The proportion of patients receiving guideline "not recommended" regimens (virologically undesirable or overlapping toxicities) was <1% after 1997. VA prescribing trends generally predated guideline recommendations by 6 to 12 months. CONCLUSIONS: VA prescribing patterns for ARV initiation adhere to treatment guidelines that maximize safety. Guidelines designed to maximize efficacy were not followed as stringently. Evaluating clinical practice patterns against contemporary treatment guidelines can inform guideline development.     

Successful introduction of routine opt-out HIV testing in antenatal care in Botswana

BACKGROUND: Botswana has high HIV prevalence among pregnant women (37.4% in 2003) and provides free services for prevention of mother-to-child transmission (PMTCT) of HIV. Nearly all pregnant women (>95%) have antenatal care (ANC) and deliver in hospital. Uptake of antenatal HIV testing was low from 1999 through 2003. In 2004, Botswana's President declared that HIV testing should be "routine but not compulsory" in medical settings. METHODS: Health workers were trained to provide group education and recommend HIV testing as part of routine ANC services. Logbook data on ANC attendance, HIV testing, and uptake of PMTCT interventions were reviewed before and after routine testing training, and ANC clients were interviewed. RESULTS: After routine testing started, the percentage of all HIV-infected women delivering in the regional hospital who knew their HIV status increased from 47% to 78% and the percentage receiving PMTCT interventions increased from 29% to 56%. ANC attendance and the percentage of HIV-positive women who disclosed their HIV status to others remained stable. Interviews indicated that ANC clients supported the policy. CONCLUSIONS: Routine HIV testing was more accepted than voluntary testing in this setting and led to substantial increases in the uptake of testing and PMTCT interventions without detectable adverse consequences. Routine testing in other settings may strengthen HIV care and prevention efforts.     

Barriers to antiretroviral adherence for patients living with HIV infection and AIDS in Botswana

BACKGROUND: Botswana has the highest rate of HIV infection in the world, estimated at 36% among the population aged 15-49 years. To improve antiretroviral (ARV) treatment delivery, we conducted a cross-sectional study of the social, cultural, and structural determinants of treatment adherence. METHODS: We used both qualitative and quantitative research methodologies, including questionnaires and interviews with patients receiving ARV treatment and their health care providers to elicit principal barriers to adherence. Patient report and provider estimate of adherence (>/=95% doses) were the primary outcomes. RESULTS: One hundred nine patients and 60 health care providers were interviewed between January and July 2000; 54% of patients were adherent by self-report, while 56% were adherent by provider assessment. Observed agreement between patients and providers was 68%. Principal barriers to adherence included financial constraints (44%), stigma (15%), travel/migration (10%), and side effects (9%). On the basis of logistic regression, if cost were removed as a barrier, adherence is predicted to increase from 54% to 74%. CONCLUSIONS: ARV adherence rates in this study were comparable with those seen in developed countries. As elsewhere, health care providers in Botswana were often unable to identify which patients adhere to their ARV regimens. The cost of ARV therapy was the most significant barrier to adherence.     

Prevention of mother-to-child transmission of HIV--successes, controversies and critical questions

In a relatively short period of time enormous strides have been made in the field of mother-to-child transmission (MTCT) of HIV. Timing, mechanisms and risk factors for transmission have been elucidated and a large number of drug regimens have been shown to effectively reduce the risk of HIV infection in the child. A number of observations can be gleaned from the work that has been done to design and implement HIV perinatal prevention programs. First, pregnancy is a critical time to identify women with HIV infection and to link them and their families to ongoing HIV care and treatment In addition to providing perinatal prevention intervention, pregnancy serves as an entry point into the health-care system. There is a unique opportunity to link prevention and treatment efforts, two programmatic areas often viewed as conflicting and competing. Second, the evolution of perinatal prevention in high-resource settings and, to an increasing extent, more resource-constrained areas, reflects the interplay of science and public-health policy. Results of clinical trials and epidemiologic studies have progressively provided recommendations and guidelines for HIV counseling, testing and treatment for perinatal prevention. In many ways, the successes of perinatal prevention in the USA attest to the success of the dynamic interaction between health, science, and public policy. There is great hope and expectation that the next decade will be equally successful as care and treatment becomes increasingly available in resource-constrained settings. Third, a key element of perinatal prevention is the provision of safe and effective family planning to women of childbearing years. Many women, particularly in low-resource settings, have multiple pregnancies, influenced by cultural imperatives and limited access to safe, affordable contraception. Enhancing these services will enable women to make informed decisions about their health, their families, and their futures. Finally, it is critical to remember that primary prevention of HIV infection in women holds the true key to perinatal prevention. While work must continue to identify more efficacious and safe regimens to prevent MTCT, preventing women from becoming HIV-infected should remain the true measure of success.     

Nevirapine concentrations in newborns receiving an extended prophylactic regimen

BACKGROUND: The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. METHODS: As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration >100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14. RESULTS: The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels <100 ng/mL, although only 1 neonate had no detectable NVP. CONCLUSION: Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol.     

Investigation of mother-to-child transmission of HIV in pregnancy and among HIV-exposed infants accessing care at a PMTCT clinic in southwest Nigeria

Background: Over 90% of infant acquired immunodeficiency syndrome (AIDS) cases have been through mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Consequent to this, prevention of mother-to-child transmission (PMTCT) programs have instituted as dual purposes for prevention of HIV transmission from mother to child and enrollment of infected pregnant women and their families into antiretroviral treatment (ART) program. However, there are still some breakthrough infections and challenges. Therefore, this study was designed to assess risk of HIV transmission among HIV-exposed infants on follow-up at a PMTCT clinic in an antiretroviral (ARV) referral health facility in southwest Nigeria.

Methods: A cohort of 60 purposively recruited consenting pregnant women referred to PMTCT HIV clinic in Ibadan, southwest Nigeria were enrolled and followed up for 1 year (2015–2016). A well-structured epidemiological questionnaire was used to capture all relevant information. Data were then analyzed by SPSS version 21 (St. Louis, MO, USA), while bivariate and multivariate analyses were used to identify associations.

Results: A total of 44 mothers and their infants were available for the analysis with an attrition rate of 26.7%. The mean age of mothers at enrollment to follow-up was 32.9 years (SD = 4.2 years). Two (4.5%, 95% CI: 7.2–12.3%) of the infants were HIV positive by DNA PCR test. There was no linear relationship between age of the mothers with CD4 count or viral load both before and after delivery but there was a significant positive relationship with year on ARV (r = 0.318, 95% CI: 0.024–0.562). Infants of rural dwelling mothers were at 3.39 (adjusted odds ratio (AOR) = 3.39, 95% CI: 1.32, 2.29) times higher risk of vertical HIV transmission compared to those of urban dwelling mothers. Infants delivered at home had 2.61(AOR = 2.61, 95% CI: 1.59, 7.91) times higher risk of MTCT compared to those delivered at health institution. Mixed feeding was also another important predictor in which the risk of MTCT was about two (AOR = 2.21, 95% CI: 0.68, 9.97) times higher compared to exclusive breastfeeding.

Conclusions: There was a high risk of MTCT of HIV among exposed infants on follow-up at the PMTCT clinic of Adeoyo Maternity Teaching referral hospital. Our findings will assist health policy makers in providing important information capable of enhancing assurance HIV control in such population and in raising the standard of PMTCT program in Nigeria.     

Wasting during pregnancy increases the risk of mother-to-child HIV-1 transmission

OBJECTIVES: To examine whether wasting during pregnancy, as measured by weight loss and low weight gain, is associated with increased mother-to-child transmission (MTCT) of HIV-1. METHODS: This was a cohort study in Dar es Salaam, Tanzania, among 957 HIV-1-infected pregnant women. Weight was measured at the first prenatal visit and every month thereafter until delivery. Weight loss was defined as a weekly rate of weight gain 0 and /=167 g/wk, weight loss during pregnancy was related to higher risk of intrauterine MTCT (adjusted relative risk [RR] = 2.32, 95% CI = 1.23-4.36, P = 0.009), HIV positive at birth or fetal death (RR = 2.13, 95% CI = 1.40-3.24, P = 0.0004), and HIV positive at birth or early neonatal death (RR = 1.96, 95% CI = 1.26-3.07, P = 0.003). The rate of weight gain during the 3rd trimester was inversely related to the risk of intrapartum/early breast-feeding transmission (adjusted P value, test for trend = 0.05). CONCLUSIONS: Weight loss during pregnancy increases the risk of early MTCT. Identifying causes of wasting during pregnancy may provide clues for new strategies to prevent MTCT.     

Mother-to-child transmission of HIV-1: advances and controversies of the twentieth centuries

Mother-to-child transmission (MTCT) is the overwhelming source of HIV-1 infection in young children. According to the World Health Organization (WHO), during the year 2003, despite effective antiretroviral (ARV) therapy, there were approximately 700,000 new infections in children worldwide, the majority of whom were from resource-limited countries. Alternative protocols to the long-course and complex regimens of ARV drugs, which in high-income countries have almost eradicated HIV MTCT, have been shown to reduce early transmission rates by 38-50%. However, the accumulation of drug resistance and the long-term toxicities of ARVs mean that alternative approaches need to be developed. Furthermore, transmission via breastfeeding, which accounts for one third of all transmission events, can reduce the benefits of short-course therapies given to women for the prevention of MTCT. The complex mechanisms and determinants of HIV-1 MTCT and its prevention in the different routes of transmission are still not completely understood. Despite the large contribution that many international agencies have made during the past 10-15 years in support of observational and intervention trials, as well as basic scientific research, HIV-1 MTCT intervention trials and basic research often are not integrated, leading to the generation of a fragmented picture. Maternal RNA levels, CD4+ T-cell counts, mode of delivery and gestational age were shown to be independent factors associated with transmission. However, these markers are only partial surrogates and cannot be used as absolute predictors of MTCT of HIV-1. Studies on the role of viral characteristics, immune response and host genomic polymorphisms did not always achieve conclusive results. Although CCR5-using viruses are preferentially carried by HIV-1 infected women as well as transmitted to their infants, the 32-basepair deletion of the CCR5 gene was not shown to influence perinatal MTCT. X4 viruses are apparently hampered in MTCT, although transmission of syncytium-inducing (SI) viruses, which use CXCR4, can occur when the mother carries such virus. Recently, there has been evidence of multiple virus variant transmission during peripartum MTCT. If viral escape from cytotoxic T-lymphocyte (CTL) recognition was repeatedly detected in transmitting mothers, no conclusive results were obtained on the role of the humoral immune response. The hypothesis on the mechanisms of selection during MTCT are still an open question, and include possibly that the transmitted variant is derived from a variant in the mother that escaped immune response, or that transmission is a stochastic event with the random transmission of a limited number of viral variants, or otherwise that selection occurs in the infant through a replication advantage of some transmitted viral variants. Although global access to ARV therapy certainly remains the primary goal to achieve the immediate reduction of MTCT of HIV-1, it is also evident that new and additional innovative strategies are needed.     

Sexual and reproductive life of women informed of their HIV seropositivity: a prospective cohort study in Burkina Faso.

BACKGROUND: In the context of the DITRAME-ANRS 049 research program that evaluated interventions aimed at reducing mother-to-child transmission of HIV (MTCT) in Bobo-Dioulasso (Burkina Faso), Voluntary HIV counseling and testing (VCT) services were established for pregnant women. HIV-infected women were advised to disclose their HIV serostatus to their male partners who were also offered VCT, to use condoms to reduce sexual transmission, and to choose an effective contraception method to avoid unwanted pregnancies. This study aimed at assessing how HIV test results were shared with male sexual partners, the level of use of modern contraceptive methods, and the pregnancy incidence among these women informed of the risks surrounding sexual and reproductive health during HIV infection. METHODS: From 1995 to 1999, a quarterly prospective follow-up of a cohort of HIV-positive women. RESULTS: Overall, 306 HIV-positive women were monitored over an average period of 13.5 months following childbirth, accounting for a total of 389 person-years. The mean age at enrollment in the cohort was 25.1 (standard deviation, 5.2 years). In all, 18% of women informed their partners, 8% used condoms at each instance of sexual intercourse to avoid HIV transmission, and 39% started using hormonal contraception. A total of 48 pregnancies occurred after HIV infection was diagnosed, an incidence of 12.3 pregnancies per 100 person-years. Pregnancy incidence was 4 per 100 person-years in the first year of monitoring and this rose significantly to 18 per 100 person-years in the third year. The only predictor of the occurrence of a pregnancy after HIV diagnosis was the poor outcome of the previous pregnancy (stillbirth, infant death). Severe immunodeficiency and change in marital status were the only factors that prevented the occurrence of a pregnancy after HIV diagnosis. CONCLUSION: Our study shows a poor rate of HIV test sharing and a poor use of contraceptive methods despite regular advice and counseling. Pregnancy incidence remained comparable with the pregnancy rate in the general population. To improve this situation, approaches for involving husbands or partners in VCT and prevention of MTCT interventions should be developed, evaluated, and implemented.