Articles tagged as "Eliminate new HIV infections among children"

Safety of tenofovir during pregnancy

Safety of tenofovir during pregnancy for the mother and fetus: a systematic review.

Wang L, Kourtis AP, Ellington S, Legardy-Williams J, Bulterys M. Clin Infect Dis. 2013 Dec;57(12):1773-81. doi: 10.1093/cid/cit601. Epub 2013 Sep 17.

Tenofovir disoproxil fumarate (TDF) safety during pregnancy has important public health implications. This review summarizes TDF safety during pregnancy, focusing on pregnancy outcomes, congenital anomaly risk, and other potential toxicities on neonates. Although information is limited, TDF appears to be safe during pregnancy. In 6 studies of human immunodeficiency virus type 1 (and/or hepatitis B virus)-infected women receiving TDF during pregnancy, adverse events were mild to moderate; none were considered to be TDF-related. Five studies that followed in utero TDF-exposed infants showed no increased risk of growth or bone abnormalities. One study showed slightly lower infant height at age 1 year, but the significance is unclear. The Antiretroviral Pregnancy Registry database, with 1 800 pregnancies exposed to TDF in the first trimester, does not indicate increased congenital anomaly risk with TDF exposure. More evidence collected prospectively, ideally with bone density measurements and randomized trial design, will be optimal to determine the effects of antenatal TDF exposure on children's health.

Abstract  Full-text [free] access

Editor’s notes: Tenofovir is a well-tolerated antiretroviral drug which is effective against HIV and hepatitis B. Due to these favourable characteristics and its once-daily dosing, tenofovir is increasingly used in clinical practice. As a result, more women are exposed to this drug at conception and during pregnancy. Tenofovir is classified by the US Food and Drug Administration as a pregnancy category B drug. This means that there is insufficient evidence to determine risk in humans. The authors of this paper provide the reader with an updated systematic review of the safety of tenofovir in pregnancy. Amongst the studies looking at adverse events in infants and mothers, no serious adverse events occurred which were attributed to tenofovir. Likewise, no study identified an increased risk of growth or bone abnormalities in infants up to two years of age. These studies need to be interpreted with caution as many studies had small sample sizes and in some studies the duration of exposure to tenofovir was short (single dose-seven days). Arguably, the most reassuring evidence comes from the antiretroviral pregnancy registry database report, which showed no increased risk of congenital anomalies amongst 1 800 infants exposed to tenofovir in utero. This systematic literature review notes the paucity of available evidence to guide decision-making and highlights the need for further studies to determine the risk to humans of tenofovir exposure during pregnancy.

HIV Treatment
Africa, Asia, Europe, Northern America
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The importance of continued infant prophylaxis against HIV-1 transmission throughout breastfeeding

Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

Fowler MG, Coovadia H, Herron CM, Maldonado Y, Chipato T, Moodley D, Musoke P, Aizire J, Manji K, Stranix-Chibanda L, Fawzi W, Chetty V, Msweli L, Kisenge R, Brown E, Mwatha A, Eshleman SH, Richardson P, Allen M, George K, Andrew P, Zwerski S, Mofenson LM, Jackson JB; for the HPTN 046 Protocol Team. J Acquir Immune Defic Syndr. 2013 Nov 1. [Epub ahead of print]

Background: HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to NVP or placebo to prevent postnatal infection: we report final 18 month outcomes.

Methods: Randomized, placebo-controlled trial in four African countries. Infant diagnostic HIV testing was done regularly from birth, through 18 months. Kaplan-Meier analysis was used to assess 18 month cumulative infant HIV infection, HIV infection/or death and mortality rates.

Results: Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower, among infants receiving daily NVP from 6 weeks to 6 months 1.1% (95% CI 0.2-1.8%), compared to placebo: 2.4% (95% CI 1.3-2.6%), p=0.049; but not significantly lower thereafter. Eighteen month postnatal infection rates were low: 2.2% [95% CI 1.1-3.3%] versus 3.1% [95% CI 1.9-4.4%], respectively, p=0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18 month postnatal infection rates (0.5%, 95% CI 0.0-1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI 1.9-5.5%); and infants of mothers with CD4 >350/mm not receiving ART (4.8%, 95% CI 2.7-6.8%), (p=0.46). There were no differences in adverse events between study arms.

Conclusion: This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age six weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.

Abstract access 

Editor’s notes: Despite increased coverage of antiretroviral treatment for pregnant women living with HIV, approximately 230 000 children are newly infected with HIV each year. The HPTN046 trial was designed to test the efficacy and safety of extended once daily infant nevirapine (NVP) prophylaxis to six months, among breastfed, HIV exposed infants who had received 6 weeks of NVP and were uninfected at age 6 weeks.  The trial was implemented at a time when breastfeeding was recommended to stop by 6 months for HIV exposed infants. This paper reports final HIV transmission, infant HIV-free survival and overall infant survival through to 18 months of age. Disappointingly, there was little evidence of a difference in postnatal HIV transmission rates between study arms (cumulative 18 month HIV-free survival rate of 94.5% in the NVP arm versus 93.3% in the placebo arm; p=0.32) and similar infant survival rates (95.3% versus 95.9%; p=0.72). The results of the 6 month follow-up, and the low transmission rate among infants whose mothers were on ART throughout 18 month follow-up emphasize the importance of ART provision to mothers who require it for their own health, and infant prophylaxis during the breastfeeding period (now recommended as 12 months). 

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Congenital CMV infection in Zambia – further population-based studies needed

High rates of congenital cytomegalovirus (CMV) infections linked with maternal HIV infection among neonatal admissions at a large referral centre in sub-Saharan Africa.

Mwaanza N, Chilukutu L, Tembo J, Kabwe M, Musonda K, Kapasa M, Chabala C, Sinyangwe S, Mwaba P, Zumla A, Bates M. Clin Infect Dis. 2013 Nov 21. [Epub ahead of print]

Congenital cytomegalovirus (CMV) infection is the major infectious cause of birth defects and hearing loss globally. There is a growing recognition of the potential clinical impact of congenital CMV infections in high seroprevalence settings.

Methods: A cross-sectional study of neonatal admissions at a large referral centre in sub-Saharan Africa to determine the prevalence of both symptomatic and asymptomatic congenital CMV infection. Real Time PCR was used to screen DNA-extracted from sera, urine and saliva, and an ELISA assay was used to screen sera for anti-CMV IgM. Multivariate binary logistic regression was used to identify risk factors associated with increased odds of congenital CMV infection.

Results: Congenital CMV was detected in 3.8% (15/395) of neonates. Among these cases 40% (6/15) presented with jaundice, one of which also had petechiae. Congenital CMV infection was detected in 11.4% (9/79) [6.1-20.3%] of neonates born to HIV-infected mothers and both maternal HIV (OR 6.661 [2.126-20.876], p=0.001) and jaundice (OR 5.701 [1.776-18.306], p=0.003) were independently linked with significantly increased odds of congenital CMV infection.

Conclusion: Congenital and early infant CMV infections may have important consequences for child health in sub-Saharan Africa and other high HIV and CMV seroprevalence populations globally.

Abstract access

Editor’s notes: Congenital cytomegalovirus (CMV) can lead to hearing impairment and neurodevelopmental delay, but few studies have estimated the prevalence of congenital CMV infection in Sub-Saharan Africa. This may be because it has been assumed that clinical impact of congenital CMV is likely to be low, resulting primarily from maternal re-infections or reactivations of CMV. This study recruited from an inpatient neonatal population in Lusaka, Zambia, and found a high prevalence of congenital CMV (3.8%) in this population and a strong association with maternal HIV infection.  The number of cases was small but a substantial minority (40%) were symptomatic. Limitations of the study include selection biases due to the recruitment process, and lack of information on antiretroviral status of the mother. Despite these, the study highlights the need for further, population-based studies in high HIV prevalence settings to assess the prevalence and risk factors for congenital CMV more widely, including the role of ART and maternal viral shedding on risk of transmission. 

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“Cure” of HIV in a baby?

Absence of Detectable HIV-1 Viremia after Treatment Cessation in an Infant.

Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M, Chun TW, Strain M, Richman D, Luzuriaga K. N Engl J Med. 2013 Oct 23. [Epub ahead of print]

An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing to high-risk exposure. ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection. After therapy was discontinued (when the child was 18 months of age), levels of plasma HIV-1 RNA, proviral DNA in peripheral-blood mononuclear cells, and HIV-1 antibodies, as assessed by means of clinical assays, remained undetectable in the child through 30 months of age. This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection.

Abstract access

Editor’s notes: This case report received wide media attention when it was presented at the Conference for Retroviruses and Opportunistic Infections in March 2013. A child, born to a mother with untreated HIV disease at the time of delivery, received combination antiretroviral therapy (ART) starting 30 hours after birth. ART was discontinued in an unplanned interruption at 18 months. When the child returned to care, the HIV viral load was undetectable, and has remained so to 36 months without re-initiation of treatment. The authors argue that the detectable viral load in the child at birth was unlikely to be due to transfusion of the mother’s blood to the child during labour. Also, that the child likely acquired HIV prior to the onset of labour, so ART was unlikely to have acted as post exposure prophylaxis. Although some of the tests for residual infection have been equivocal, the fact that the HIV viral load has not rebounded after treatment was discontinued suggests that HIV reservoirs were either not established or were abated. 

Since this is a case report with no comparator group, it remains uncertain to what degree early ART initiation influenced the outcome in this child. However, the observation that, 18 months after discontinuing ART, this child has an undetectable viral load raises the possibility that ART initiation very early after infection could profoundly alter the course of HIV infection.

Northern America
United States of America
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LPV/r mono-therapy: a future option for preventing mother to child transmission?

Lopinavir/Ritonavir monotherapy as a nucleoside analogue-sparing strategy to prevent HIV-1 mother-to-child transmission: The ANRS 135 PRIMEVA phase 2/3 randomized trial.

Tubiana R, Mandelbrot L, Le Chenadec J, Delmas S, Rouzioux C, Hirt D, Treluyer JM, Ekoukou D, Bui E, Chaix ML, Blanche S, Warszawski J; ANRS 135 PRIMEVA (Protease Inhibitor Monotherapy Evaluation)Study Group. Clin Infect Dis. 2013 Sep;57(6):891-902. doi: 10.1093/cid/cit390. Epub 2013 Jun 12.

Background:  Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is usually based on zidovudine-containing regimens, despite potential toxicities. This multicenter trial evaluated whether lopinavir/ritonavir (LPV/r) monotherapy in HIV type 1-infected women not requiring antiretrovirals for themselves could control maternal viral load (VL).

Methods:  Overall, 105 pregnant women with baseline VL <30 000 copies/mL and CD4 ≥350 cells/µL were randomized to start open-label LPV/r 400/100 mg twice daily alone (monotherapy group, n = 69) or combined with zidovudine/lamivudine 300/150 mg twice daily (triple therapy group, n = 36) from 26 gestational weeks to delivery. According to a Fleming 2-stage phase 2 design, monotherapy was considered to be efficacious if at least 59 patients achieved VL <200 copies/mL at 8 weeks of treatment (primary endpoint). Secondary endpoints were VL at delivery and tolerance.

Results:  Monotherapy was efficacious as defined: 62 women in the monotherapy group achieved VL <200 copies/mL at 34 weeks' gestation (ie, 8 weeks of treatment; 89.9%; 95% confidence interval [CI], 80.2%-95.8%). At delivery, proportions with VL <200 copies/mL were similar in the monotherapy and triple therapy groups (92.8% vs 97.2%; P = .66); however, fewer had VL <50 copies/mL in the monotherapy group (78.3% vs 97.2%; P = .01). Changes for intolerance were less frequent in the monotherapy than in the triple therapy group (1.4% vs 11.1%, respectively; P = .046). Cesarean delivery and preterm delivery rates did not differ. All children were liveborn; 1 case of HIV-1 transmission occurred in the triple therapy group, none in the monotherapy group (95% CI upper limit = 5.2%).

Conclusions:  LPV/r monotherapy achieved satisfactory virologic efficacy in women treated solely for PMTCT, providing proof of concept for future nucleoside-sparing strategies.

Clinical Trials Registration. NCT00424814; Afssaps AIDS Clinical Trial Group A61176-34.

Abstract access 

Editor’s notes: Treating pregnant mothers with antiretroviral therapy (ART) is an effective strategy for eliminating new HIV infections in children. Currently recommended regimens comprise two nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir boosted protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI). However, as NRTIs’ can cross the placenta and have a natural affinity for mitochondrial and nuclear human DNA, concerns have been raised that children exposed to NRTIs in-utero are at risk of long-term toxicity. In this ‘proof-of-concept’ randomized controlled trial (RCT) the researchers compared a NRTI-sparing regimen (ritonavir boosted lopinavir [LPV/r] mono-therapy) to standard of care (2 NRTIs plus LPV/r) in pregnant women who did not require ART for their own health. Mono-therapy was found to have satisfactory virological efficacy in terms of the primary end-point, maternal viral load (VL) <200 copies/ml at 8 weeks; however these women were more likely to have low level viraemia at birth (78.3% versus 97.2% with VL<50 copies/ml [p=0.01] with only one woman on mono-therapy having VL >400 copies/ml). As the authors state, the implications of low level maternal viraemia at birth are uncertain, with the targets set in national guidelines varying between 1000 copies/ml in USA to 50 copies/ml in UK. These results indicate that NRTI-sparing regimens, such as protease inhibitor (PI) mono-therapy, may be an alternative strategy for preventing mother to child transmission in an immune-competent woman with low viral loads in high-income settings. However, as this strategy requires serial VL monitoring, PI mono-therapy is unlikely to be a viable option for many low- and middle income countries. 

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High prevalence of primary resistance in HIV-infected pregnant women

HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania.

Vairo F, Nicastri E, Liuzzi G, Chaula Z, Nguhuni B, Bevilacqua N, Forbici F, Amendola A, Fabeni L, De Nardo P, Perno CF, Cannas A, Sakhoo C, Capobianchi MR, Ippolito G. BMC Infect Dis. 2013 Sep 21;13(1):439. [Epub ahead of print]

Background: HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naive to antiretrovirals.

Methods: Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected.

Results: Drug-resistance analysis was performed on 97 naive infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes.

Conclusion: Our study reports an 11.9% prevalence of primary drug resistance in naive HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

Abstract Full-text [free] access

Editor’s notes: This nested cross-sectional study of HIV-positive pregnant women in a rural area of Tanzania found a high prevalence of HIV-1 drug resistance. To be eligible for inclusion in this study, patients had to have been diagnosed with HIV during their current pregnancy and have had no prior exposure to antiretroviral therapy (including single dose nevirapine). Thus, transmitted drug resistance is a more likely explanation than acquired drug resistance. These findings, which are consistent with other reports from the region, raise concerns about the future use of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in the region, whether this is for preventing mother to child transmission or as a recommended first-line regimen.

United Republic of Tanzania
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Adolescent mothers are not linking to care

HIV-Infected adolescent mothers and their infants: low coverage of HIV services and high risk of HIV transmission in KwaZulu-Natal, South Africa.  

Horwood C, Butler LM, Haskins L, Phakathi S, Rollins N. PLoS One. 2013 Sep 20;8(9):e74568. doi: 10.1371/journal.pone.0074568.

Objectives: Rates of pregnancy and HIV infection are high among South African adolescents, yet little is known about rates of mother-to-child transmission of HIV (MTCT) in this group. We report a comparison of the characteristics of adolescent mothers and adult mothers, including HIV prevalence and MTCT rates.

Methods: We examined patterns of health service utilization during the antenatal and early postnatal period, HIV prevalence and MTCT amongst adolescent (20-years-old) and adult (20 to 39-years-old) mothers with infants aged 16 weeks attending immunization clinics in six districts of KwaZulu-Natal between May 2008 and April 2009.

Findings: Interviews were conducted with 19 093 mothers aged between 12 and 39 years whose infants were aged 16 weeks. Most mothers had attended antenatal care four or more times during their last pregnancy (80.3%), and reported having an HIV test (98.2%). A greater proportion of HIV-infected adult mothers, compared to adolescent mothers, reported themselves as HIV-positive (41.2% vs. 15.9%, p,0.0001), reported having a CD4 count taken during their pregnancy (81.0% vs. 66.5%, p,0.0001), and having received the CD4 count result (84.4% vs. 75.7%, p,0.0001). Significantly fewer adolescent mothers received the recommended PMTCT regimen. HIV antibody was detected in 40.4% of 7 800 infants aged 4–8 weeks tested for HIV, indicating HIV exposure. This was higher among infants of adult mothers (47.4%) compared to adolescent mothers (17.9%, p,0.0001). The MTCT rate at 4–8 weeks of age was significantly higher amongst infants of adolescent mothers compared to adult mothers (35/325 [10.8%] vs. 185/2,800 [6.1%], OR 1.7, 95% CI 1.2–2.4).

Conclusion: Despite high levels of antenatal clinic attendance among pregnant adolescents in KwaZulu-Natal, the MTCT risk is higher among infants of HIV-infected adolescent mothers compared to adult mothers. Access to adolescent-friendly family planning and PMTCT services should be prioritised for this vulnerable group.

Abstract  Full-text [free] access

Editorial notes:   Adolescents have high pregnancy rates in South Africa, with one third reporting a pregnancy by the age of 20 years. Adolescents are also at disproportionately high risk of HIV infection. A high proportion of lifetime HIV risk is accrued before age 25 years. This study from KwaZulu-Natal, comparing health service utilization and mother-to-child transmission rates between adult and adolescent mothers, report some concerning disparities.  The majority of mothers had attended frequently for antenatal care and been tested for HIV.  Adolescent mothers were more likely to have tested late (in the last trimester of pregnancy or postnatally), less likely to have had a CD4 count or to have received an effective prevention of mother-to-child transmission regimen.  In addition, adolescent mothers were more likely to be living in adverse social conditions than their adult counterparts.  These disparities resulted in higher HIV mother-to-child transmission rates among adolescents than in adults.

The findings highlight the differential service delivery, access to care and service uptake in the adolescent age-group.  Given the high rates of pregnancy and HIV in this age-group, there is a need to focus on adolescents if elimination of new HIV infections among children is to be achieved. Strategies to make reproductive health services more accessible to adolescents are urgently required. This must include addressing the particular vulnerabilities of adolescents as well as training of healthcare providers.     

South Africa
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Improved PMTCT strategies substantially reduce transmission rates in South Africa

Reduction in perinatal HIV infections in KwaZulu-Natal, South Africa, in the era of more effective prevention of mother to child transmission interventions (2004-2012)

Moodley P, Parboosing R, Moodley D., Acquir Immune Defic Syndr. 2013 Jul 1;63(3):410-5. doi: 10.1097/QAI.0b013e3182926931.

Objective: To describe a trend in perinatal HIV transmission associated with the implementation of rapidly changing prevention of mother to child transmission (PMTCT) interventions from 2004 to 2012.

Method: Retrospective analysis of infant HIV polymerase chain reaction results of infants from 2004 to 2012 archived from a Laboratory Information System.

Setting: KwaZulu-Natal, South Africa.

Main outcome measure: HIV infection in infants aged 4-8 weeks.

Results:  The proportion of 4- to 8-week-old infants who tested HIV polymerase chain reaction positive decreased significantly (P < 0.0001) from 27.5% in 2004 to 2.9% in 2012. The reduction rates in perinatal HIV infections in 4- to 8-week-old HIV-exposed infants decreased significantly (P < 0.0001) by 48.7% following single-dose nevirapine (sdNVP) (2005 to April 2008), 68.4% with zidovudine from 28 weeks and sdNVP together with triple antiretroviral therapy for women with CD4 cell count < 200 cells/mm (May 2008-April 2010), and 89.5% with zidovudine from 14 weeks, sdNVP, and triple antiretroviral therapy for women with CD4 cell count < 350 cells/mm (May 2010-December 2012).

Conclusions: We show an almost 10-fold reduction in mother to child transmission from 2004 to 2012 in infants aged 4-8 weeks during a rapid implementation of more complex and robust PMTCT interventions. The significant reductions in mother to child transmission in the South African PMTCT program are encouraging for a middle-income country with the second highest antenatal HIV prevalence in the world.

Abstract access

Editor’s notes: This retrospective study analyzed data from routine infant HIV tests, and thus provides empirical evidence of the effect of implementation of rapidly changing PMTCT guidelines in this high HIV prevalence setting over the past decade.  During this period, HIV prevalence among women attending antenatal clinics did not change substantially (between 37-39%), but the prevalence among HIV exposed infants aged 4-8 weeks decreased dramatically from 27.6% (95%CI 19.1-36.2) in 2004 to 2.9% (95%CI 2.8-3.0%) in 2012.  A similar decrease was seen among infants aged eight weeks to 15 months (30.1% in 2004 to 7.3% in 2012). The higher rate in the older infants is likely due to transmission through breastfeeding. The data from 2010-2012 are based on implementation of WHO Option A, and this changed in April 2013 to Option B (triple ARVs starting at 14 weeks gestation and continued intrapartum and through delivery if not breastfeeding, or until one week after cessation of all breastfeeding, with the infant given daily NVP or AZT from birth through age 4-6 weeks regardless of infant feeding method).  The expectation is that Option B, and B Plus (lifelong ART for all HIV-infected pregnant women regardless of CD4 count) should reduce MTCT to below 5% by 2015.  

South Africa
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AZT monotherapy vs. combination ART for prevention of vertical transmission in Ukraine

Impact of expanded access to combination antiretroviral therapy in pregnancy: results from a cohort study in Ukraine.

Bailey H, Townsend CL, Semenenko I, Malyuta R, Cortina-Borja M, Thorne C; Ukraine European Collaborative Study Group in EuroCoord., Bull World Health Organ. 2013;91(7):491-500. doi: 10.2471/BLT.12.114405

Objectives: To investigate the scale-up of antenatal combination antiretroviral therapy (cART) in Ukraine since this became part of the national policy for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV).

Methods: Data on 3 535 HIV-positive pregnant women who were enrolled into the Ukraine European Collaborative Study in 2008-2010 were analysed. Factors associated with receipt of zidovudine monotherapy (AZTm) - rather than cART - and rates of mother-to-child transmission (MTCT) of HIV were investigated.

Findings: cART coverage increased significantly, from 22% of deliveries in 2008 to 61% of those in 2010. After adjusting for possible confounders, initiation of antenatal AZTm - rather than cART - was associated with cohabiting (versus being married; adjusted prevalence ratio, aPR: 1.09; 95% confidence interval, CI: 1.02-1.16), at least two previous live births (versus none; aPR: 1.22; 95% CI: 1.11-1.35) and a diagnosis of HIV infection during the first or second trimester (versus before pregnancy; aPR: 1.11; 95% CI: 1.03-1.20). The overall MTCT rate was 4.1% (95% CI: 3.4-4.9); 42% (49/116) of the transmissions were from the 8% (n = 238) of women without antenatal ART. Compared with AZTm, cART was associated with a 70% greater reduction in the risk of MTCT (adjusted odds ratio: 0.30; 95% CI: 0.16-0.56).

Conclusion: Between 2008 and 2010, access to antenatal cART improved substantially in Ukraine, but implementation of the World Health Organization's Option-B policy was slow. For MTCT to be eliminated in Ukraine, improvements in the retention of women in HIV care and further roll-out of Option B are urgently needed.

Abstract Full-text [free] access

Editor’s notes:  Elimination of infant infections by 2015 is a global target. The guideline for PMTCT has moved from using Option A (AZT monotherapy or AZTm) and Option B (combination ART in pregnancy or cART) to the most recent recommendation in 2013 of Option B+ (initiation of life-long ART for all HIV-infected pregnant women).  

Coverage of cART in Ukraine increased significantly over the study period.  The majority of women who did not receive any ART were either diagnosed before conception and lost to care or were diagnosed before delivery.  cART was associated with a significantly lower risk of MTCT than AZTm even after adjusting for duration of ART and despite women with advanced disease more likely to be given cART . Women were diagnosed during pregnancy were however, more likely to get AZTm probably because there was less opportunity to counsel them about cART.  Notably, those who were co-habiting or had had two or more previous pregnancies were also less likely to receive cART.  This group had a lower educational status, a factor associated with AZTm receipt.  Underlying contextual factors such as practical and financial barriers to attending for care in this group may explain why they may have received AZTm, as clinicians are less likely to prescribe cART to infrequent attenders. 

This study demonstrates that engagement with and retention in care of women is a pre-requisite for successful scale-up of cART. This is going to be an even more important consideration if Option B+ is to be successfully implemented.

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Missed opportunities for vaginal delivery among women with HIV in Europe

Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery.

 Aebi-Popp K, Mulcahy F, Glass TR, Rudin C, Martinez de Tejada B, Bertisch B, Fehr J, Grawe C, Scheibner K, Rickenbach M, Hoesli I, Thorne C; for the European Collaborative Study in EuroCoord and the Swiss Mother & Child HIV Cohort Study., J Acquir Immune Defic Syndr. 2013 Jul 9. [Epub ahead of print]

Introduction:  Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe.

Methods: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre-or post-publication of national guidelines recommending vaginal delivery.

Results: Overall, 2 663 women with 3 013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2 020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2 377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2 354) before to 7% (42/599) after the change in guidelines (P < 0.001).

Conclusion: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

Abstract access

Editor’s notes: In 1999, following a randomised controlled trial showing a lower risk of vertical HIV transmission among babies delivered by elective Caesarean section, pregnant women with HIV were advised to deliver by elective Caesarean section where this option was available to them. In the last decade, accumulating observational data suggested that women taking combination ART with suppressed viral load who delivered vaginally were at very low risk of vertical transmission. This led to revised guidelines allowing vaginal delivery for women with suppressed viral load on combination ART.

This analysis of European data (with largest numbers contributed by Italy, Belgium and Switzerland) shows the increasing number of women having vaginal deliveries over the last decade. However, a substantial proportion of women had unsuppressed viral load at the time of delivery, and some received no ART prior to delivery, suggesting the need to engage pregnant women with HIV in care earlier.  In addition, the data suggest that more women who have suppressed viral load could safely undergo vaginal delivery.  The proportion of infants acquiring HIV infection in the period after introduction of guidelines allowing vaginal delivery was 0.6%, which is lower than 1.6% prior to the guideline change but suggests that further efforts are required to ensure that all children in Europe are born HIV-free.

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