Articles tagged as "Eliminate new HIV infections among children"

Effective pre-conception ART eliminates mother-to-child transmission

No perinatal hiv-1 transmission from women with effective antiretroviral therapy starting before conception.

Mandelbrot L, Tubiana R, Le Chenadec J, Dollfus C, Faye A, Pannier E, Matheron S, Khuong MA, Garrait V, Reliquet V, Devidas A, Berrebi A, Allisy C, Elleau C, Arvieux C, Rouzioux C, Warszawski J, Blanche S, Group A-ES. Clin Infect Dis. 2015 Dec 1;61(11):1715-25. doi: 10.1093/cid/civ578. Epub 2015 Jul 21.

Background: The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT.

Methods: A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation.

Results: The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9-8.2).

Conclusions: Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL.

Abstract access 

Editor’s notes: The risk of HIV transmission from mother-to-child is around 15-45% in the absence of maternal antiretroviral therapy (ART). This study illustrates that the risk of mother-to-child transmission is virtually eliminated when ART is started prior to conception and plasma viral load (VL) is undetectable at delivery. These findings provide further evidence supporting the implementation of Option B+ (lifelong ART as early as possible in all HIV-positive pregnant women regardless of CD4 count and VL) in low-income countries. In these settings, effectiveness of pre-conception ART will be dependent on retention in care so that women remain virologically suppressed for subsequent pregnancies. Robust surveillance data of pregnancy outcomes and other short-term and long-term risks of ART on the foetus, such as congenital malformations, and on the infant, such as pre-term birth, are also necessary to confirm that the benefit of pre-conception ART outweighs any harm.

Europe
France
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HIV tests at church-based baby showers raise odds of testing 11-fold for pregnant women

Effect of a congregation-based intervention on uptake of HIV testing and linkage to care in pregnant women in Nigeria (baby shower): a cluster randomised trial.

Ezeanolue EE, Obiefune MC, Ezeanolue CO, Ehiri JE, Osuji A, Ogidi AG, Hunt AT, Patel D, Yang W, Pharr J, Ogedegbe G. Lancet Glob Health. 2015 Nov;3(11):e692-700. doi: 10.1016/S2214-109X(15)00195-3.

Background: Few effective community-based interventions exist to increase HIV testing and uptake of antiretroviral therapy (ART) in pregnant women in hard-to-reach resource-limited settings. We assessed whether delivery of an intervention through churches, the Healthy Beginning Initiative, would increase uptake of HIV testing in pregnant women compared with standard health facility referral.

Methods: In this cluster randomised trial, we enrolled self-identified pregnant women aged 18 years and older who attended churches in southeast Nigeria. We randomised churches (clusters) to intervention or control groups, stratified by mean annual number of infant baptisms (<80 vs ≥80). The Healthy Beginning Initiative intervention included health education and on-site laboratory testing implemented during baby showers in intervention group churches, whereas participants in control group churches were referred to health facilities as standard. Participants and investigators were aware of church allocation. The primary outcome was confirmed HIV testing. This trial is registered with ClinicalTrials.gov, identifier number NCT 01795261.

Findings: Between Jan 20, 2013, and Aug 31, 2014, we enrolled 3002 participants at 40 churches (20 per group). 1309 (79%) of 1647 women attended antenatal care in the intervention group compared with 1080 (80%) of 1355 in the control group. 1514 women (92%) in the intervention group had an HIV test compared with 740 (55%) controls (adjusted odds ratio 11.2, 95% CI 8.77-14.25; p<0.0001).

Interpretation: Culturally adapted, community-based programmes such as the Healthy Beginning Initiative can be effective in increasing HIV screening in pregnant women in resource-limited settings.

Abstract Full-text [free] access

Editor’s notes: HIV testing is a key entry point for prevention of mother-to-child transmission. Community-based, decentralised HIV testing outside health facilities can increase uptake of testing among pregnant women, but this does not always follow through into good linkage to care.

In Nigeria faith-based organisations have a strong social network and a wider presence than health facilities. This trial co-ordinated churches in predominantly Christian southeast Nigeria to identify pregnant women early and organise a baby shower where on-site laboratory tests were provided. To avoid stigma the programme offered testing for five other conditions alongside HIV. Women who tested positive for HIV infection were linked to care and followed up at a post-delivery baby reception at the church. Women in the programme arm were more likely to have an HIV test and if positive they were more likely to access care before delivery and to start ART during pregnancy.

The results illustrate the benefits of engagement with faith-based organisations to reach communities that are poorly served by health facilities. The fact male partners played a role in the baby shower may have increased uptake, as pregnant women are more likely to accept HIV testing when male partners are also involved. The main costs were Mama Packs (a gift of essentials for a safe delivery, presented at the baby shower) and integrated lab tests. The activity was so popular that communities continued with it after the trial ended. The programme is now being adapted for mosques in northern Nigeria and Hindu temples in India. 

Africa
Nigeria
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Contraception for women on ART – a balancing act

Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study.

Patel RC, Onono M, Gandhi M, Blat C, Hagey J, Shade SB, Vittinghoff E, Bukusi EA, Newmann SJ, Cohen CR. Lancet HIV. 2015 Nov;2(11):e474-82. doi: 10.1016/S2352-3018(15)00184-8. Epub 2015 Oct 22.

Background: Concerns have been raised about efavirenz reducing the effectiveness of contraceptive implants. We aimed to establish whether pregnancy rates differ between HIV-positive women who use various contraceptive methods and either efavirenz-based or nevirapine-based antiretroviral therapy (ART) regimens.

Methods: We did this retrospective cohort study of HIV-positive women aged 15-45 years enrolled in 19 HIV care facilities supported by Family AIDS Care and Education Services in western Kenya between Jan 1, 2011, and Dec 31, 2013. Our primary outcome was incident pregnancy diagnosed clinically. The primary exposure was a combination of contraceptive method and efavirenz-based or nevirapine-based ART regimen. We used Poisson models, adjusting for repeated measures, and demographic, behavioural, and clinical factors, to compare pregnancy rates among women receiving different contraceptive and ART combinations.

Findings: 24 560 women contributed 37 635 years of follow-up with 3337 incident pregnancies. In women using implants, adjusted pregnancy incidence was 1.1 per 100 person-years (95% CI 0.72-1.5) for nevirapine-based ART users and 3.3 per 100 person-years (1.8-4.8) for efavirenz-based ART users (adjusted incidence rate ratio [IRR] 3.0, 95% CI 1.3-4.6). In women using depot medroxyprogesterone acetate, adjusted pregnancy incidence was 4.5 per 100 person-years (95% CI 3.7-5.2) for nevirapine-based ART users and 5.4 per 100 person-years (4.0-6.8) for efavirenz-based ART users (adjusted IRR 1.2, 95% CI 0.91-1.5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, had 3.1-4.1 higher rates of pregnancy than did those using implants, with 1.6-2.8 higher rates in women using efavirenz-based ART.

Interpretation: Although HIV-positive women using implants and efavirenz-based ART had a three-times higher risk of contraceptive failure than did those using nevirapine-based ART, these women still had lower contraceptive failure rates than did those receiving all other contraceptive methods except for intrauterine devices and permanent methods. Guidelines for contraceptive and ART combinations should balance the failure rates for each contraceptive method and ART regimen combination against the high effectiveness of implants.

Abstract access 

Editor’s notes: Contraceptive use by women living with HIV who wish to prevent pregnancy remains a key component of the strategy to eliminate new HIV infections among children. Progesterone-based implants are the most effective reversible contraceptive method, but there is some evidence to suggest that their efficacy may be reduced in women receiving efavirenz (EFV)-based antiretroviral therapy (ART).

Overall contraceptive use in these women of childbearing age was low – 70% of the time women were using no contraception or less effective methods only (condoms or natural methods). Overall pregnancy rates were low with the hormonal implant, broadly equivalent to women with intrauterine devices and much lower than with depot injectable and oral contraceptive methods. There was some evidence that the rate of pregnancy in women using the implant was higher for women on EFV-based ART compared to women on nevirapine-based ART. However, the rate of pregnancy remained lower than with injectable or oral contraceptives.

Although this may provide some support to the evidence of reduced implant efficacy with EFV-based ART, it is clear that this can still be an effective contraceptive method. This evidence seems unlikely to change existing WHO recommendations that all forms of contraception should be available to women living with HIV. The low rate of contraceptive use highlights the need to improve access for women living with HIV to quality integrated sexual and reproductive health services. The data from this study suggest that for women wishing to avoid pregnancy, the choice of contraceptive method may be more important than the choice of ART regimen.  

Africa
Kenya
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One in 10 mothers living with HIV are unaware of their status

Missed opportunities along the prevention of mother-to-child transmission services cascade in South Africa: uptake, determinants, and attributable risk (the SAPMTCTE).

Woldesenbet S, Jackson D, Lombard C, Dinh TH, Puren A, Sherman G, Ramokolo V, Doherty T, Mogashoa M, Bhardwaj S, Chopra M, Shaffer N, Pillay Y, Goga A, South African PET. PLoS One. 2015 Jul 6;10(7):e0132425. doi: 10.1371/journal.pone.0132425. eCollection 2015.

Objectives: We examined uptake of prevention of mother-to-child HIV transmission (PMTCT) services, predictors of missed opportunities, and infant HIV transmission attributable to missed opportunities along the PMTCT cascade across South Africa.

Methods: A cross-sectional survey was conducted among 4-8 week old infants receiving first immunisations in 580 nationally representative public health facilities in 2010. This included maternal interviews and testing infants' dried blood spots for HIV. A weighted analysis was performed to assess uptake of antenatal and perinatal PMTCT services along the PMTCT cascade (namely: maternal HIV testing, CD4 count test/result, and receiving maternal and infant antiretroviral treatment) and predictors of dropout. The population attributable fraction associated with dropouts at each service point are estimated.

Results: Of 9803 mothers included, 31.7% were HIV-positive as identified by reactive infant antibody tests. Of these 80.4% received some form of maternal and infant antiretroviral treatment. More than a third (34.9%) of mothers dropped out from one or more steps in the PMTCT service cascade. In a multivariable analysis, the following characteristics were associated with increased dropout from the PMTCT cascade: adolescent (<20 years) mothers, low socioeconomic score, low education level, primiparous mothers, delayed first antenatal visit, homebirth, and non-disclosure of HIV status. Adolescent mothers were twice (adjusted odds ratio: 2.2, 95% confidence interval: 1.5-3.3) as likely to be unaware of their HIV-positive status and had a significantly higher rate (85.2%) of unplanned pregnancies compared to adults aged ≥20 years (55.5%, p = 0.0001). A third (33.8%) of infant HIV infections were attributable to dropout in one or more steps in the cascade.

Conclusion: A third of transmissions attributable to missed opportunities of PMTCT services can be prevented by optimizing the uptake of PMTCT services. Identified risk factors for low PMTCT service uptake should be addressed through health facility and community-level interventions, including raising awareness, promoting women education, adolescent focused interventions, and strengthening linkages/referral-system between communities and health facilities.

Abstract  Full-text [free] access

Editor’s notes: WHO recommends a comprehensive approach to prevention of mother-to-child transmission. This includes primary prevention of HIV among women of childbearing age, prevention of unintended pregnancies among women living with HIV, prevention of HIV transmission from a woman living with HIV to her infant and the provision of appropriate treatment, care and support to mothers living with HIV, their children and families.

This study assessed the uptake of antenatal and perinatal prevention of mother-to-child transmission services at four key stages along the prevention of mother-to-child transmission cascade (maternal HIV testing, CD4 count test/result, receiving maternal antiretroviral treatment and infant antiretroviral treatment).

Of all mothers included in the study, 31.7% were HIV-positive as identified by reactive infant antibody tests. Some 11% of HIV-positive mothers were reportedly unaware of their HIV-positive status. Being an adolescent was the strongest predictor of unawareness of HIV-positive status.

Overall 35% of mothers missed at least one step in the cascade. Dropout from the cascade, for all stages combined, accounted for 33.8% of HIV infections among infants, and maternal HIV status knowledge contributed to nearly half of this total.

The authors suggest that reported unawareness of being HIV-positive could be due to recent maternal infection or seroconversion during pregnancy. They call for improved repeat HIV testing during antenatal care and at delivery to identify new infections, and increased coverage of testing and counselling on safe sex for couples.

Interestingly the authors found that most pregnancies were unplanned (60%), demonstrating an important gap in the WHO prevention of mother-to-child transmission comprehensive strategy. Adolescent mothers (< 20 years) had a significantly higher rate of unplanned pregnancies compared to adult mothers. The authors suggest that programmes are necessary for sexually active adolescent girls to reduce both unplanned pregnancies and the risk of contracting HIV during conception or thereafter. 

Africa
South Africa
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Benefits to women and newborns by integrating HIV and ANC services

Integration of PMTCT and antenatal services improves combination antiretroviral therapy (cART) uptake for HIV-positive pregnant women in Southern Zambia - a prototype for option B+?

Herlihy JM, Hamomba L, Bonawitz R, Goggin CE, Sambambi K, Mwale J, Musonda V, Musokatwane K, Hopkins KL, Semrau K, Hammond EE, Duncan J, Knapp AB, Thea DM. J Acquir Immune Defic Syndr. 2015 Jul 15. [Epub ahead of print]

Background: Early initiation of combination anti-retroviral therapy (cART) for HIV-positive pregnant women can decrease vertical transmission to less than 5%. Programmatic barriers to early cART include decentralized care, disease stage assessment delays, and loss-to-follow-up.

Intervention: Our intervention had 3 components: integrated HIV and antenatal services in one location with one provider; lab courier to expedite CD4 counts; and community-based follow-up of women-infant pairs to improve PMTCT attendance. Pre-intervention HIV-positive pregnant women were referred to HIV clinics for disease stage assessment and cART initiation for advanced disease CD4< 350 or WHO stage >2.

Methods: We employed a quasi-experimental design with pre/post-intervention evaluations at 6 government antenatal clinics (ANC) in Southern Province, Zambia. Retrospective clinical data were collected from clinic registers during a 7-month baseline period. Post-intervention data were collected from all ART-naive, HIV-positive pregnant women and their infants presenting to ANC from December 2011-June 2013.

Results: Data from 510 baseline women-infant pairs were analyzed and 624 pregnant women were enrolled during the intervention period. Proportion of HIV-positive pregnant women receiving CD4 counts increased from 50.6% to 77.2%, RR=1.81 95% CI: 1.57-2.08; p<0.01. Proportion of cART-eligible pregnant women initiated on cART increased from 27.5% to 71.5% RR=2.25, 95% CI: 1.78-2.83; p<0.01. Proportion of eligible HIV-exposed infants with documented 6-week HIV PCR test increased from 41.9% to 55.8%, RR=1.33, 95% CI: 1.18-1.51; p<0.01.

Conclusion: Integration of HIV care into ANC and community-based support improved uptake of CD4 counts, proportion of cART-eligible women initiated on cART and infants tested.

Abstract access 

Editor’s notes: Integrating HIV services into other elements of health care, such as family planning or maternal health services, can increase uptake of HIV testing and antiretroviral therapy (ART) initiation. For pregnant women, timely HIV diagnosis and treatment can greatly reduce the probability of mother-to-child transmission. Integrating HIV services into maternal antenatal clinic (ANC) services therefore has potential to bring benefit to women living with HIV and their newborns. This paper describes an experimental study in which six ANC clinics in Zambia – all with high attendance and in provinces with high HIV prevalence – integrated HIV testing and treatment into their routine ANC services. This integration took the form of training existing ANC providers in HIV diagnosis and management; providing a rapid CD4 measurement service; and training volunteer lay counsellors to maintain regular contact with mothers living with HIV to improve ART initiation and adherence. The programme was associated with dramatic increases in ART initiation, early testing of infants and early ART initiation. The integrated approach used here has potential to improve prevention of mother-to-child transmission services. This is done through streamlined combination antiretroviral therapy (cART) initiation and decreasing time gaps in referral models. The approach assists in reducing HIV associated stigma and fear as the clinics offer maternal/child health services as well as HIV care. The clinics offer continuity through a community lay counsellor who follows the mother infant pair through pregnancy, delivery and breastfeeding. Further work is necessary to evaluate strategies for HIV care retention through similar models using community health workers and family-centric HIV care.

Africa
Zambia
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Where are the weak links in prevention of mother-to-child HIV transmission programmes?

Reconstructing the PMTCT cascade using cross-sectional household survey data: The PEARL Study.

Chi BH, Tih PM, Zanolini A, Stinson K, Ekouevi DK, Coetzee D, Welty TK, Bweupe M, Shaffer N, Dabis F, Stringer EM, Stringer JS. J Acquir Immune Defic Syndr. 2015 Jun 11. [Epub ahead of print]

Background: Given the ambitious targets to reduce pediatric AIDS worldwide, ongoing assessment of programs to prevent mother-to-child HIV transmission (PMTCT) is critical. The concept of a "PMTCT cascade" has been used widely to identify bottlenecks in program implementation; however, most efforts to reconstruct the cascade have relied on facility-based approaches that may limit external validity.

Methods: We analyzed data from the PEARL household survey, which measured PMTCT effectiveness in 26 communities across Zambia, South Africa, Cote d'Ivoire, and Cameroon. We recruited women who reported a delivery in the past two years. Among mothers confirmed to be HIV-infected at the time of survey, we reconstructed the PMTCT cascade with self-reported participant information. We also analyzed data about the child's vital status; for those still alive, HIV testing was performed via DNA PCR.

Results: Of the 976 eligible women, only 355 (36%) completed every step of the PMTCT cascade. Among the 621 mother-child pairs who did not, 22 (4%) reported never seeking antenatal care, 103 (17%) were not tested for HIV during pregnancy, 395 (64%) reported testing but never received their HIV-positive result, 48 (8%) did not receive maternal antiretroviral prophylaxis, and 53 (9%) did not receive infant antiretroviral prophylaxis. The lowest prevalence of infant HIV infection or death was observed in those completing the cascade (10%, 95%CI: 7%-12%).

Conclusions: Future efforts to measure population PMTCT impact should incorporate dimensions explored in the PEARL Study - including HIV testing of HIV-exposed children in household surveys - to better understand program effectiveness.

Abstract access 

Editor’s notes: Programmes to prevent the transmission of HIV from mother-to-child can virtually eliminate transmission when conducted with adequate coverage and quality. This population-based study recruited women living with HIV who had given birth in the past 24 months from four sub-Saharan African countries including Cameroon, Côte d’Ivoire, South Africa and Zambia. The 976 mothers allowed their children to be tested for HIV, and reported on the level of maternal health services they received for that child, the “prevention of mother-to-child HIV transmission cascade”. While 98% of mothers had at least one contact with antenatal care services, only 36% eventually received services considered to be adequate for preventing transmission of HIV to their children. This study is notable for highlighting exactly where coverage gaps exist along the treatment pathway. In particular, 53% of mothers did not receive the result of an HIV test, and so would not have received follow-up services to prevent transmission. As a population-based study, these data provide a fuller picture of service coverage which cannot be captured by traditional monitoring and evaluations systems. These results can inform where systems strengthening must occur along the “prevention of mother-to-child HIV transmission cascade”, so that transmission risk is minimized for all children born to women living with HIV.

Africa
Cameroon, Côte d'Ivoire, South Africa, Zambia
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Harnessing the successful political prioritisation of HIV to reduce the burden of congenital syphilis

Prevention of mother-to-child transmission of syphilis and HIV in China: What drives political prioritization and what can this tell us about promoting dual elimination?

Wu D, Hawkes S, Buse K. Int J Gynaecol Obstet. 2015 Apr 29. pii: S0020-7292(15)00202-7. doi: 10.1016/j.ijgo.2015.04.005. [Epub ahead of print]

Objective: The present study aims to identify reasons behind the lower political priority of mother-to-child transmission (MTCT) of syphilis compared with HIV, despite the former presenting a much larger and growing burden than the latter, in China, over the 20 years prior to 2010.

Methods: We undertook a comparative policy analysis, based on informant interviews and documentation review of control of MTCT of syphilis and HIV, as well as nonparticipant observation of relevant meetings/trainings to investigate agenda-setting prior to 2010.

Results: We identified several factors contributing to the lower priority accorded to MTCT of syphilis: relative neglect at a global level, dearth of international financial and technical support, poorly unified national policy community with weak accountability mechanisms, insufficient understanding of the epidemic and policy options, and a prevailing negative framing of syphilis that resulted in significant stigmatization.

Conclusion: A dual elimination goal will only be reached when prioritization of MTCT of syphilis is enhanced in both the international and national agendas.

Abstract  Full-text [free] access

Editor’s notes:  In 2009, China had nearly 11 000 reported cases of congenital syphilis, compared to 57 cases of mother-to-child HIV transmission, yet congenital syphilis was not a policy priority. The authors investigate and compare the policy responses to the two infections in order to understand the determinants of prioritisation in Chinese health policy. The national policy response to the mother-to-child transmission of HIV highlights the importance of global agendas. These include reporting mechanisms, international financial and technical assistance, credible indicators, as well as cohesive national policy communities that coalesce around a formal mechanism of coordination and policy influence, namely the Chinese National Centre for Women and Children’s Health. In addition, the specific national policy environment and other focusing events were critical to the prioritisation of the mother-to-child transmission of HIV. The new leadership was moving towards a socio-economic equality agenda, and the recent severe acute respiratory syndrome (SARS) outbreak had further underscored the importance of controlling infectious diseases. Alongside this, the national ‘blood selling’ scandal, during which hundreds of thousands of rural Chinese acquired HIV through blood selling in the 90s, was receiving increasing attention in international media. This contributed to a different framing of the HIV issue, away from the stigmatising ‘immoral’ narrative to an ‘innocent victims’ narrative. Congenital syphilis, unfortunately, continued to suffer from a stigmatising framing. However, delivery platforms for the effective prevention of mother-to-child transmission of HIV have been established and could be used for a dual control and elimination approach, with greater health benefits. The authors conclude that greater policy prioritisation could be achieved with a more nuanced framing of the two infections as being linked when it comes to underlying vulnerability and feasibility of solutions. It will require a strong partnership and collaboration between the mother-to-child transmission of syphilis and HIV policy communities.       

Asia
China
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Early postnatal cytomegalovirus infection may predict subsequent HIV transmission through breastfeeding

Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers.

Chang TS, Wiener J, Dollard SC, Amin MM, Ellington S, Chasela C, Kayira D, Tegha G, Kamwendo D, Jamieson DJ, van der Horst C, Kourtis AP; BAN Study Team. AIDS. 2015 Apr 24;29(7):831-6. doi: 10.1097/QAD.0000000000000617

Background: Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown.

Methods: The Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi, randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms - mother (triple regimen), infant (nevirapine), or neither - for 28 weeks of breastfeeding, followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity, mortality, or postnatal HIV acquisition.

Results: At 24 weeks of age, CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%, and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05).

Conclusion: Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding, pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV.

Abstract access 

Editor’s notes: Studies have illustrated that mother-to-child HIV transmission is more frequent among neonates with congenital cytomegalovirus (CMV) infection. Infants co-infected with HIV and CMV have higher rates of HIV disease progression and death. This study using data and samples of infant plasma and peripheral blood mononuclear cells are from the Breastfeeding, Antiretrovirals and Nutrition (BAN) randomised, controlled clinical trial (RCT). The study examines whether postnatal CMV infection in the infant is associated with HIV transmission through breastfeeding. The study investigates the relationship between postnatal antiretroviral therapy and postnatal CMV acquisition. The data suggests that early postnatal CMV infection in an HIV-exposed uninfected infant may predict subsequent HIV transmission through breastfeeding and infant mortality. The study confirmed previous findings that approximately 70% of breastfed infants born to mothers living with HIV in low-income settings acquire CMV infection by six months of age. However, the study did not find an association between maternal antiretroviral therapy and the risk of postnatal CMV transmission. It is important to note that in the RCT, antiretroviral therapy was only initiated at the onset of labour.  The effect of maternal antiretroviral therapy taken earlier in pregnancy on the prevention or delay of CMV acquisition remains unknown, although a few observational studies have found that maternal antiretroviral therapy reduces congenital and early postnatal CMV infection. It is biologically plausible that antiretroviral therapy reduces or prevents CMV reactivation in the mother, thus preventing transient episodes of maternal CMV viraemia. This mechanism could explain reduced CMV transmission to the infant (be that before or after birth). HIV-exposed but uninfected infants experience higher morbidity and mortality; any such disease attributable to CMV could therefore potentially be reduced by initiation of antiretroviral therapy earlier in pregnancy.

Africa
Malawi
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Elimination of mother-to-child HIV transmission: still a pipe dream?

HIV testing among pregnant women who attend antenatal care in Malawi.

Tenthani L, Haas AD, Egger M, van Oosterhout JJ, Jahn A, Chimbwandira F, Tal K, Myer L, Estill J, Keiser O. J Acquir Immune Defic Syndr. 2015 May 6. [Epub ahead of print] 

Malawi adopted the Option B+ strategy in 2011. Its success in reducing MTCT depends on coverage and timing of HIV testing. We assessed HIV status ascertainment and its predictors during pregnancy. HIV status ascertainment was 82.3% (95%-CI 80.2-85.9) in the pre-Option B+ period and 85.7% (95%-CI 83.4-88.0) in the Option B+ period. Higher HIV ascertainment was independently associated with higher age, attending ANC more than once, and registration in 2010. The observed high variability of HIV ascertainment between sites (50.6%-97.7%) and over time suggests that HIV test kits shortages and insufficient numbers of staff posed major barriers to reducing MTCT.

Abstract access 

Editor’s notes: UNAIDS has called for an end to mother-to-child HIV transmission through the Global Plan towards the elimination of new infections among children and keeping their mothers alive. WHO guidelines on the use of antiretroviral medicines for treating and preventing HIV infection in 2013 recommends two options for pregnant and breastfeeding women. One of which is lifelong antiretroviral therapy (ART) for all pregnant women living with HIV regardless of CD4 count or disease stage, commonly referred to as Option B+. The Global Plan requires that 90% of all women living with HIV have access to ART. The success of the Global Plan will depend on sufficient numbers of women being tested for HIV.

This study includes data from 19 secondary and primary health facilities offering antenatal care in Malawi, the first country to introduce the Option B+ strategy in 2011. Introduction of the Option B+ strategy did not result in a significant change in the proportion of women who underwent HIV testing.  HIV ascertainment varied widely across facilities from 50% to 98%, and fluctuated greatly within sites over short time periods. The observed sudden decreases in numbers of women who received an HIV test suggest that important barriers to HIV testing exist at facility level. Previous studies have illustrated that temporary shortages of HIV testing kits and staff interrupt regular antenatal (ANC) HIV testing in health facilities. Women who had had multiple ANC visits were more likely to have had their HIV status ascertained, likely because multiple visits increased their chance to attend when staff and kits were available. Unfortunately, this study was unable to determine individual-level factors associated with HIV testing not having occurred.

We now have highly effective programmes that can virtually eliminate new HIV infections  among children globally. To attain this goal, urgent attention must be paid to strengthening health systems. Elimination of new infections among children will require attention to the whole cascade of care from diagnosis of HIV, through to provision of results and treatment and supporting women to take ART consistently.   

Africa
Malawi
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Better retention in care among HIV-exposed infants whose mothers receive combination ART

Maternal combination antiretroviral therapy is associated with improved retention of HIV-exposed infants in Kinshasa, Democratic Republic of Congo.

Feinstein L, Edmonds A, Okitolonda V, Cole SR, Van Rie A, Chi BH, Ndjibu P, Lusiama J, Chalachala JL, Behets F. J Acquir Immune Defic Syndr. 2015 Apr 13. [Epub ahead of print]

Background: Programs to prevent mother-to-child HIV transmission (PMTCT) are plagued by loss to follow-up (LTFU) of HIV-exposed infants. We assessed if providing combination antiretroviral therapy (cART) to HIV-infected mothers was associated with reduced LTFU of their HIV-exposed infants in Kinshasa, DR Congo.

Methods: We constructed a cohort of mother-infant pairs using routinely collected clinical data. Maternal cART eligibility was based on national guidelines in effect at the time. Infants were considered LTFU following three failed tracking attempts after a missed visit or if more than six months passed since they were last seen in clinic. Statistical methods accounted for competing risks (e.g. death).

Results: 1318 infants enrolled at a median age of 2.6 weeks (interquartile range [IQR]: 2.1-6.9), at which point 24% of mothers were receiving cART. Overall, 5% of infants never returned to care following enrollment and 18% were LTFU by 18 months. The 18-month cumulative incidence of LTFU was 8% among infants whose mothers initiated cART by infant enrollment and 20% among infants whose mothers were not yet on cART. Adjusted for baseline factors, infants whose mothers were not on cART were over twice as likely to be LTFU, with a subdistribution hazard ratio of 2.75 (95% confidence limit: 1.81, 4.16). The association remained strong regardless of maternal CD4 count at infant enrollment.

Conclusion: Increasing access to cART for pregnant women could improve retention of HIV-exposed infants, thereby increasing the clinical and population-level impacts of PMTCT interventions and access to early cART for HIV-infected infants.

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Editor’s notes: An estimated one third of all HIV-exposed infants are lost to follow up (LTFU) by three months in sub-Saharan Africa.  Regular follow-up of HIV-exposed infants is necessary to ensure that they are provided with prophylactic drugs, have an opportunity for early infant diagnosis, and if HIV-positive that they are started on combination antiretroviral treatment (cART) as soon as possible.  This study using routinely collected programmatic data (2007 - 2013) in Kinshasa found that infants whose mothers had not yet initiated cART were more than twice as likely to be LTFU as infants whose mothers had initiated cART. An important point to highlight is that this study was unable to tease out what proportion of the effect of maternal cART on infant LTFU was attributable to reduction in infant mortality. There are few data on factors that contribute to LTFU in HIV-exposed infants. The available evidence suggests that structural barriers, including transport, waiting time and cost, affect retention in care. 

Africa
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