HIV This Week

Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: the Mitra Plus study.

Kilewo C, Karlsson K, Ngarina M, Massawe A, Lyamuya E, Swai A, Lipyoga R, Mhalu F, Biberfeld G; Mitra Plus Study Team. J Acquir Immune Defic Syndr. 2009;52:406-16.

The main aim of this study was to reduce breast-milk transmission of HIV-1 by treating HIV-1-infected women with antiretroviral therapy (ART) during breastfeeding. Mitra Plus was an open-label, nonrandomized, prospective cohort study. HIV-1-infected pregnant women in Dar es Salaam were treated with zidovudine (ZDV) + lamivudine (3TC) + nevirapine (NVP). NVP was later replaced by nelfinavir for mothers with CD4 cell counts >200 cells per microlitre or with adverse reaction to NVP. Antiretroviral therapy was initiated at 34 weeks of gestation. For women with symptomatic HIV infection or CD4 cell counts below 200 cells per microlitre, antiretroviral therapy was started earlier if possible. Treatment of the mothers was stopped at 6 months except for those mothers who needed antiretroviral therapy for their own health. The infants received ZDV + 3TC for 1 week after birth. Mothers were advised to exclusively breastfeed and to wean abruptly between 5 and 6 months. Transmission of HIV-1 was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breastfeeding population of the Petra trial arm A. There were 441 infants included in the analysis of HIV-1 transmission. The cumulative transmission of HIV-1 was4.1 % [95% confidence interval (CI): 2.2 to 6.0] at 6 weeks, 5.0% (95% CI: 2.9 to 7.1) at 6 months, and 6.0% (95% CI: 3.7 to 8.3) at 18 months after delivery. The cumulative risk of HIV transmission between 6 weeks and 6 months was 1.0% and between 6 months and 18 months 1.1%. The cumulative HIV infection or death rate was 8.6% (95% CI: 6.0 to 11.2) at 6 months and 13.6% (95% CI: 10.3 to 16.9) at 18 months after delivery. Viral load at enrolment and duration of antiretroviral therapy before delivery were significantly associated with transmission but CD4 cell count at enrolment was not. The median time of breastfeeding was 24 weeks. The transmission in the Mitra Plus study was about half of the transmission in the breastfeeding population in the Petra trial arm A at 6 months after delivery (adjusted relative hazard = 0.49, P < 0.001). The combined outcome HIV infection or death was significantly lower in the Mitra Plus study than in the breastfeeding population in the Petra trialarm A at 18 months (adjusted relative hazard = 0.61, P = 0.007). NVP-related mucocutaneous rash was demonstrated in 6.5% of 429 NVP-exposed women. The incidence of NVP-related grade 3 or 4 hepatotoxicity was low (0.5%). Antiretroviral therapy given to HIV-infected mothers in late pregnancy and during breastfeeding resulted in a low postnatal HIV transmission similar to that previously demonstrated in the Mitra study in Dar es Salaam using infant prophylaxis with 3TC during breastfeeding. The extended maternal prophylaxis with antiretroviral therapy for prevention of mother-to-child transmission of HIV-1 for breastfeeding mothers who do not need antiretroviral therapy for their own health should be further evaluated and compared with the use of infant postnatal antiretroviral prophylaxis regarding safety and cost-effectiveness.

For access to abstract click here: 1 

Editors’ note: These Mitra Plus study findings from Tanzania of low HIV transmission through breastfeeding when mothers receive antiretroviral treatment, whether they need it for their own health or not, may well have informed the new WHO ‘rapid advice’ documents released last week. Although the option remains (Option A) to provide AZT only from as early as 14 weeks of pregnancy, followed by AZT and 3TC during labour and delivery and for 7 days postpartum – with breastfeeding babies then receiving nevirapine until one week after all exposure to breast milk has ended – a new option called Option B has emerged. It includes maternal triple antiretroviral prophylaxis from as early as 14 weeks and continuing until 1 week after all exposure of the infant to breast milk ends. Changes such as these will bring us closer to the goal of virtually eliminating mother-to-child transmission of HIV.

Breastfeeding with maternal antiretroviral therapy or formula feeding to prevent HIV postnatal mother-to-child transmission in Rwanda.

Peltier CA, Ndayisaba GF, Lepage P, van Griensven J, Leroy V, Pharm CO, Ndimubanzi PC, Courteille O, Arendt V. AIDS. 2009 23:2415-23.

The aim of the study was to assess the 9-month HIV-free survival of children with two strategies to prevent HIV mother-to-child transmission in a nonrandomized interventional cohort study. Four public health centres in Rwanda enrolled participants between May 2005 and January 2007. All consenting HIV-infected pregnant women were included. Women could choose the mode of feeding for their infant: breastfeeding with maternal antiretroviral therapy for 6 months or formula feeding. All received antiretroviral therapy from 28 weeks of gestation. Nine-month cumulative probabilities of HIV transmission and HIV-free survival were determined using the Kaplan-Meier method and compared using the log-rank test. Determinants were analysed using a Cox model analysis. Of the 532 first-liveborn infants, 227 (43%) were breastfeeding and 305 (57%) were formula feeding. Overall, seven (1.3%) children were HIV-infected of whom six were infected in utero. Only one child in the breastfeeding group became infected between months 3 and 7, corresponding to a 9-month cumulative risk of postnatal infection of 0.5% [95% confidence interval (CI) 0.1-3.4%; P = 0.24] with breastfeeding. Nine-month cumulative mortality was 3.3% (95% CI 1.6-6.9%) in the breastfeeding arm group and 5.7% (95% CI 3.6-9.2%) for the formula feeding group (P = 0.20). HIV-free survival by 9 months was 95% (95% CI 91-97%) in the breastfeeding group and 94% (95% CI 91-96%) for the formula feeding group (P = 0.66), with no significant difference in the adjusted analysis (adjusted hazard ratio for breastfeeding: 1.2 (95% CI 0.5-2.9%). Maternal antiretroviral therapy while breastfeeding could be a promising alternative strategy in resource-limited countries.

For access to abstract click here: 1

Editors’ note: This study enrolled 562 HIV-positive pregnant women who were placed on antiretroviral treatment at 28 weeks of pregnancy regardless of CD4 count. Those who decided to formula feed stopped antiretroviral treatment after their baby’s birth if they were not eligible in Rwanda (less than 350 CD4 count) and those who decided to breastfeed continued antiretroviral treatment until 1 month after weaning their babies at 6 months of age and then stopped taking antiretroviral drugs if they were not eligible for treatment. All babies received a backbone of AZT and 3TC for seven days after they stopped being exposed to maternal antiretroviral drugs through the placenta or through breast milk to reduce the risk of resistance to the third drug (nevirapine or efavirenz). There was no difference in HIV-free survival and, amazingly, there was no significant difference in the mortality by infant feeding mode (3.3% versus 5.7%) although virtually all studies in low- and middle-income countries have shown higher mortality with formula feeding. This may be because mothers received education and good follow-up and care, regardless of the feeding option they chose. The bottom line is that the risk of HIV transmission during breastfeeding is minimal when mothers are on antiretroviral treatment, regardless of CD4 count.

A Case Series of 104 Women Infected with HIV-1 via Blood Transfusion Postnatally: High Rate of HIV-1 Transmission to Infants through Breast-Feeding.

Liang K, Gui X, Zhang YZ, Zhuang K, Meyers K, Ho DD. J Infect Dis. 2009; 200:682-6.

Liang and colleagues investigated transmission of human immunodeficiency virus type 1 (HIV-1) via breast-feeding by 104 Chinese mothers who acquired the infection through blood transfusion postnatally. Of 106 children, 38 (35.8%) were infected. All children survived to age 5 years, and their survival curve was similar to that of their mothers. These findings suggest a high rate of HIV-1 transmission via breast-feeding when mothers were infected postnatally via blood transfusion, perhaps because of the higher viremia expected during the acute phase of infection. The course of disease among infected children was significantly less rapid than that among newborns infected perinatally, suggesting that a brief window of HIV-1-free life often enables the immune system of an infant to stave off rapid disease progression.

For full text access click here: 1

Editors’ note: Although blood-selling practices were officially prohibited in China by 1995 and the Blood Transfusion Law was passed in 1998, some of the women in this cohort were infected by blood transfusions as late as 2000. This emphasises the importance of concrete local plans to reduce the time between the announcement of policies and their implementation. In this case study series of acutely infected, breastfeeding women, the HIV transmission rate of 35.8% was considerably higher than previous estimates of 9 to 16% for post-natal transmission through breast milk. The risk of HIV transmission rose significantly to 62.5% (95%CI, 35.4-84.9%) if mastitis or cracked nipples were reported. The low mortality rate of 13.2% in these children after a mean of 9.1 years in the absence of antiretroviral treatment suggests rapid evolution in the immune system capacity over the initial weeks and months of life leading to better viral control.

Lehman DA, Chung MH, Mabuka JM, John-Stewart GC, Kiarie J, Kinuthia J, Overbaugh J. J Acquir Immune Defic Syndr. 2009;51:522-9

Antiretroviral resistance after short-course regimens used to prevent mother-to-child transmission has consequences for later treatment. Directly comparing the prevalence of resistance after short-course regimens of highly active antiretroviral therapy and zidovudine plus single-dose nevirapine (ZDV/sdNVP) will provide critical information when assessing the relative merits of these antiretroviral interventions. In a clinical trial in Kenya, pregnant women were randomized to receive either ZDV/sdNVP or a short-course of highly active antiretroviral therapy through 6 months of breastfeeding. Plasma samples were collected 3-12 months after treatment cessation, and resistance to reverse transcriptase inhibitors was assessed using both a sequencing assay and highly sensitive allele-specific polymerase chain reaction assays. No mutations associated with resistance were detectable by sequencing in either the ZDV/sdNVP or highly active antiretroviral therapy arms at 3 months posttreatment, indicating that resistant viruses were not present in >20% of virus. Using allele-specific polymerase chain reaction assays for K103N and Y181C, the authors detected low levels of resistant virus in 75% of women treated with ZDV/sdNVP and only 18% of women treated with highly active antiretroviral therapy (P =0.007). Y181C was more prevalent than K103N at 3 months and showed little evidence of decay by 12 months. The study finding provides evidence that compared with ZDV/sdNVP, HAART reduces but does not eliminate nevirapine resistance.

Abstract only: 1

Editors’ note: This small Kenyan trial is the first study to compare directly the prevalence of HIV resistance after short-course antiretroviral treatment with standard prophylactic regimens. Of 58 women initially randomised, 40 women had plasma samples for analysis by sequencing assay and highly sensitive polymerase chain reaction. One study arm received zidovudine twice daily for 6 weeks before delivery, single-dose nevirapine during labour, and for the babies, single dose nevirapine. The women in the other study arm received twice-daily zidovudine, nevirapine, and 3TC for 6 weeks before and 6 months after delivery. The big difference seen in the levels of resistant virus 3 months or more after ceasing to take drugs may well be due to the fact that in the first arm, nevirapine was not accompanied by any other antiretroviral drug during labour. Antiretroviral treatment for 6 months did not eliminate nevirapine resistance, suggesting that after nevirapine is stopped, treatment cessation strategies should include temporarily continuing zidovudine and 3TC to prevent single drug pressure caused by nevirapine’s longer half-life.  

Health workers’ views on quality of prevention of mother-to-child transmission and postnatal care for HIV-infected women and their children. Nguyen TA, Oosterhoff P, Pham YN, Hardon A, Wright P. Hum Resour Health. 2009;13;7:39.

Prevention of mother-to-child transmission has been considered as not a simple intervention but a comprehensive set of interventions requiring capable health workers. Viet Nam’s extensive health care system reaches the village level, but still HIV-infected mothers and children have received inadequate health care services for prevention of mother-to-child transmission. Nguyen and colleagues report here the health workers’ perceptions on factors that lead to their failure to give good quality prevention of mother-to-child transmission services. Semistructured interviews with 53 health workers and unstructured observations in nine health facilities in Hanoi were conducted. Selection of respondents was based on their function, position and experience in the development or implementation of prevention of mother-to-child transmission policies/programmes. Factors that lead to health workers’ failure to give good quality services for prevention of mother-to-child transmission include their own fear of HIV infection; lack of knowledge on HIV and counselling skills; or high workloads and lack of staff; unavailability of HIV testing at commune level; shortage of antiretroviral drugs; and lack of operational guidelines. A negative attitude during counselling and provision of care, treating in a separate area, and avoidance of providing service at all were seen by health workers as the result of fear of being infected, as well as distrust towards almost all HIV-infected patients because of the prevailing association with antisocial behaviours. Additionally, the fragmentation of the health care system into specialized vertical pillars, including a vertical programme for HIV, is a major obstacle to providing a continuum of care. Many hospital staff were not able to provide good care or were even unwilling to provide appropriate care for HIV-positive pregnant women The study suggests that the quality of prevention of mother-to-child transmission service could be enhanced by improving communication and other skills of health workers, providing them with greater support and enhancing their motivation. Reduction of workload would also be important. Development of a practical strategy is needed to strengthen and adapt the referral system to meet the needs of patients.

For full text access click here: 1

Editors’ note : This study was undertaken to find out the opinions of health care workers, who are subjected to many accusations about gaps and weaknesses in their performance, in Hanoi’s programme to prevent mother-to-child HIV transmission. The fragmentation of the health system, their own stigma from colleagues and family because of their exposure to HIV-infected patients, and their personal fear of HIV exposure in the absence of protective clothing and post-exposure kits all combine to reduce their motivation. They identified specific problems in their training and skills updating, a heavy workload, and a lack of equipment and materials. Remedying these will take varying lengths of time but seeking pragmatic solutions in the short term to produce tangible results could improve both the quality of patient care and the job satisfaction of health care personnel looking after them.

Early assessment of the implementation of a national programme for the prevention of mother-to-child transmission of HIV in Cameroon and the effects of staff training: a survey in 70 rural health care facilities. Labhardt ND, Manga E, Ndam M, Balo JR, Bischoff A, Stoll B. Trop Med Int Health 2009; 14: 288-93.

Labhardt and colleagues set out to assess the availability of equipment and the staff’s knowledge to prevent mother-to-child Transmission (PMTCT) in rural healthcare facilities recently covered by the national PMTCT programme in Cameroon. In eight districts inventories of antiviral drugs and HIV test kits were made on site, using a standardised check-list. Knowledge of HIV and PMTCT was evaluated with a multiple-choice questionnaire based on typical clinical PMTCT cases. Staff participated subsequently in a 2-day training on HIV and the Cameroon PMTCT guidelines. Immediately after training and after 7 months, retention of knowledge was tested with the same questions but in different order and layout. Sixty two peripheral nurse-led clinics and the eight district hospitals were assessed. Whereas all district hospitals presented complete equipment, only six of the peripheral clinics (10%) were equipped with both complete testing materials and a full set of drugs to provide PMTCT. Thirty six peripheral facilities (58%) possessed full equipment for HIV-testing and 8 (13%) stocked all PMTCT drugs. Of 137 nurses, 102 (74%) agreed to the two knowledge tests. Fewer than 66% knew that HIV-diagnosis requires positive results in two different types of rapid tests and only 19% chose the right recommendation on infant-feeding for HIV-positive mothers. Correct answers on drug regimens in different PMTCT settings varied from 25% to 56%. All percentages of correct answers improved greatly with training (P < 0.001) and retention remained high 7 months after training (P < 0.001). Programmes to prevent mother-to-child transmission in settings such as rural Cameroon need to be adapted to the special needs of peripheral nurse-led clinics. Appropriate short training may considerably improve nurses’ competence in PMTCT. Other important components are regular supervision and measures to guarantee supply of equipment in rural areas.

For abstract click here : 1

Editors’ note: Cameroon has set an ambitious objective of increasing the proportion of pregnant women who have access to HIV counselling and testing services from 10% to 50% by 2010. This study, conducted four to eight months after HIV test kits and antiretroviral drugs were distributed to health districts, found inadequate supplies of materials and low levels of staff awareness and knowledge of proper procedures. A two-day training programme including case-based interactive discussions led to sustained improvement in assessment scores. Guaranteeing the flow of equipment to peripheral clinics and maintaining health care worker competence through training and supportive supervision, will be key if Cameroon is to meet its 2010 objective.

Nattabi B, Li J, Thompson SC, Orach CG, Earnest J. A Systematic Review of Factors Influencing Fertility Desires and Intentions Among People Living with HIV/AIDS: Implications for Policy and Service Delivery. AIDS Behav. 2009. DOI 10.1007/s10461-009-9537-y

With availability of antiretroviral treatments, HIV is increasingly recognised as a chronic disease people live with for many years. This paper critically reviews the current literature on fertility desires and reproductive intentions among people living with HIV and critiques the theoretical frameworks and methodologies used. A systematic review was conducted using electronic databases: ISI Web of Knowledge, Science Direct, Proquest, Jstor and CINAHL for articles published between 1990 and 2008. The search terms used were fertility desire, pregnancy, HIV, reproductive decision-making, reproductive intentions, motherhood, fatherhood and parenthood. Twenty-nine studies were reviewed. Fertility desires were influenced by a myriad of demographic, health, stigma-associated and psychosocial factors. Cultural factors were also important, particularly in Sub-Saharan Africa and Asia. Future research that examines fertility desires among people living with HIV should include cultural beliefs and practices in the theoretical framework in order to provide a holistic understanding and to enable development of services that meet the reproductive needs of people living with HIV.

Editors’ note: This interesting systematic review of studies of fertility desires and intentions reveals the importance of mixed methodologies (quantitative and qualitative) to contextualise findings and emphasises the use of theoretical frameworks relevant to cultural context to underpin study design and analyses. In most settings, people living with HIV are uncomfortable talking with health care providers about fertility issues, anticipating or experiencing biased information-giving and negative attitudes. Provision of services within a rights-based framework requires consideration of a risk-reduction approach to minimise vertical and horizontal HIV transmission through nonjudgmental care, treatment, and counselling.

Cooper D, Moodley J, Zweigenthal V, Bekker LG, Shah I, Myer L. Fertility Intentions and Reproductive Health Care Needs of People Living with HIV in Cape Town, South Africa: Implications for Integrating Reproductive Health and HIV Care Services. AIDS Behav. 2009;13:suppl1:38-46.

Tailoring sexual and reproductive health services to meet the needs of people living with the human immuno-deficiency virus (HIV) is a growing concern but there are few insights into these issues where HIV is most prevalent. This cross-sectional study investigated the fertility intentions and associated health care needs of 459 women and men, not sampled as intimate partners of each other, living with HIV in Cape Town, South Africa. An almost equal proportion of women (55%) and men (43%) living with HIV, reported not intending to have children as were open to the possibility of having children (45 and 57%, respectively). Overall, greater intentions to have children were associated with being male, having fewer children, living in an informal settlement and use of antiretroviral therapy. There were important gender differences in the determinants of future childbearing intentions, with being on antiretroviral treatment strongly associated with women’s fertility intentions. Gender differences were also apparent in participants’ key reasons for wanting children. A minority of participants had discussed their reproductive intentions and related issues with HIV health care providers. There is an urgent need for intervention models to integrate HIV care with sexual and reproduction health counselling and services that account for the diverse reproductive needs of these populations.

Editors’ note: This 2006 exploratory survey of fertility intentions among people living with HIV attending two public sector health centres in a high HIV prevalence residential area of Cape Town found that only 19% of women and 6% of men had consulted a doctor, nurse, or counsellor in HIV care about fertility intentions. Among women in HIV care, 11% had become pregnant since their HIV diagnosis, all unintentionally. Among women on antiretroviral treatment, 9% had become pregnant since starting treatment, with 30% of these pregnancies reportedly unintentional. On-site integration of sexual and reproductive health services into HIV care settings is urgently required in order to create space for discussions with women and men about their fertility intentions; to provide easy access to contraceptive measures for those who desire to postpone, prevent or discontinue pregnancies; and to provide timely antiretroviral prophylaxis to prevent mother-to-child transmission.

Deschamps MM, Noel F, Bonhomme J, Dévieux JG, Saint-Jean G, Zhu Y, Wright P, Pape JW, Malow RM. Prevention of mother-to-child transmission of HIV in Haiti. Rev Panam Salud Publica. 2009;25:24-30.

Deschamps and colleagues set out to describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in a mother-to-child transmission prevention program. Of the 650 women who participated, 73.3% received zidovudine (AZT), 2.9% received nevirapine (NVP), and 10.1% received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8% received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. Complete data were available for 348 mother-infant pairs who completed the program to prevent mother-to-child transmission of HIV. The rate of mother-to-child transmission in the study was 9.2% (95% CI:6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27% in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (chi(2) = 19.06, P < .001, log rank test). Infant survival improved with early paediatric diagnosis and antiretroviral treatment. The mother-to-child transmission prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.

Editors’ note: Over the period from 1999 to 2004 the annual number of women who agreed to undergo HIV testing at the GHESKIO clinic more than doubled and the number of HIV-positive women who enrolled in the prevention of mother-to-child transmission (PMTCT) programme quadrupled. Overall 43,173 women at higher risk of HIV exposure were tested (18.3% were HIV-positive) and 5270 were pregnant (12.3% HIV-positive). Of the 650 HIV-positive pregnant women, 28.7% did not participate in the PMTCT programme, primarily because they returned to rural areas, and only 14% were able to bring their partners in for HIV testing. After delivery, 73.9% of the women were using family planning services at 18-month follow-up compared to national uptake data of 23%. Despite persistent instability and violence in Haiti, this programme in Port-au-Prince has successfully reduced HIV transmission to infants to one-third of the historical rate. With a 2007 adult (15-49 years) HIV prevalence of 2.2% (1.9-2.5), in a league with the Bahamas, Guyana, Suriname, and Belize in the Americas, Haiti clearly needs a nationwide programme integrating family planning, voluntary counselling and testing, and HIV treatment services with good referral links between centres.

Cailhol J, Jourdain G, Coeur SL, Traisathit P, Boonrod K, Prommas S, Putiyanun C, Kanjanasing A, Lallemant M; for the Perinatal HIV Prevention Trial Group. Association of Low CD4 Cell Count and Intrauterine Growth Retardation in Thailand. J Acquir Immune Defic Syndr. 2009; 50:409-413.

Each year, intrauterine growth retardation affects 20-30 million neonates worldwide, mostly in resource-limited settings. Increased perinatal and infant mortality has been associated with intrauterine growth retardation. Some studies have suggested that HIV infection could increase the risk of intrauterine growth retardation. To confirm this hypothesis, Cailhol and colleagues examined the association between HIV-related factors and the risk of intrauterine growth retardation in Thailand. Data from a cohort of 1436 HIV-infected pregnant women enrolled in the « Perinatal HIV Prevention Trial-1 », a clinical trial conducted from 1997 to 1999 in Thailand, were analyzed using a logistic regression, adjusting for risk factors usually associated with intrauterine growth retardation. The rate of intrauterine growth retardation was 7.6%. Adjusting for a short maternal height, low body mass index, small weight gain during pregnancy, and infant female sex, a low maternal CD4 percentage was independently associated with intrauterine growth retardation (odds ratio 0.96, per 1% increment, 95% confidence interval 0.93 to 0.99, P = 0.03). The current World Health Organization recommendation to initiate combination antiretroviral therapy for immunocompromised women as early as possible during pregnancy for their own health and for the prevention of HIV mother-to-child transmission is likely to also decrease the incidence of intrauterine growth retardation. Encouraging immunocompromised HIV-infected women who plan to become pregnant to wait until immune restoration has been achieved may help to reduce the risk of intrauterine growth retardation.

Editors’ note: Intrauterine growth retardation (IUGR) is the second cause of perinatal mortality after prematurity. It is associated with higher susceptibility to various conditions in the neonatal period as well as with diseases in adulthood such as diabetes, obesity, and hypertension. This Thai study used the stringent definition of IUGR of ‘birth weight below the 10 th percentile of weight for the corresponding gestational age’, rather than the low birth weight cut-off of 2500 g which can indicate prematurity. Also it used CD4 percentage which is less variable than absolute CD4 count. The finding that CD4 percentage below the median contributed 28% of the risk of IUGR in this population gives added support to the recommendation to initiate antiretroviral treatment (as opposed to antiretroviral prophylaxis) in pregnancy for women with low CD4 counts.

Mate KS, Bennett B, Mphatswe W, Barker P, Rollins N. Challenges for routine health system data management in a large public programme to prevent mother-to-child HIV transmission in South Africa. PLoS ONE. 2009;4(5):e5483. 

Recent changes to South Africa’s prevention of mother-to-child transmission of HIV (PMTCT) guidelines have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. While programmatic efforts to reach this target are underway, obtaining complete and accurate data from clinical sites to track progress presents a major challenge. Mate and colleagues assessed the completeness and accuracy of routine PMTCT data submitted to the District Health Information System in three districts of Kwazulu-Natal province, South Africa. They surveyed the completeness and accuracy of data reported for six key PMTCT data elements between January and December 2007 from all 316 clinics and hospitals in three districts. Through visits to randomly selected sites, they reconstructed reports for the same six PMTCT data elements from clinic registers and assessed accuracy of the monthly reports previously submitted to the District Health Information System. Data elements were reported only 50.3% of the time and were “accurate” (i.e. within 10% of reconstructed values) 12.8% of the time. The data element “Antenatal Clients Tested for HIV” was the most accurate data element (i.e. consistent with the reconstructed value) 19.8% of the time, while “HIV PCR testing of baby born to HIV positive mother” was the least accurate with only 5.3% of clinics meeting the definition of accuracy. Data collected and reported in the public health system across three large, high HIV-prevalence districts was neither complete nor accurate enough to track process performance or outcomes for PMTCT care. Systematic data evaluation can determine the magnitude of the data reporting failure and guide site-specific improvements in data management. Solutions are currently being developed and tested to improve data quality.

Editors’ note: Beyond the finding of data missing at source, the weakest link in this data chain is the actual data collation at the clinic level, followed by lack of submission of data to the district level. Unless health workers are supported and supervised in the execution of data management tasks and unless data collection is designed in the first instance to be used locally to improve patient care, front line staff will not have the capacities nor perceive the value of data collection. Effective health information systems are simple, acceptable, timely, accurate, flexible, and useful. Only then do staff, who can improve clinical practice locally through analysis of performance and outcomes data, truly value them. This foundation stone is key to a health information system that helps national health systems assess progress towards established goals and plan future resource allocations.

Pai NP, Klein MB. Rapid testing at labour and delivery to prevent mother-to-child HIV transmission in developing settings: issues and challenges. Womens Health (Lond Engl). 2009;5(1):55-62.

Worldwide, approximately 2.5 million children (95% CI: 2.2-2.6) are living with HIV infection. In 2007 alone, approximately 420,000 children (95%CI:350,000-540,000) were newly infected with HIV – a vast majority of these infections were acquired through maternal-foetal transmission. Many of these infections could have been reduced by timely diagnosis and the delivery of interventions aimed at preventing mother-to-child HIV transmission. This perspective examines the attitudes preventing women from accessing HIV testing early on during pregnancy and the issues and challenges that remain in the institutionalization of interventions to prevent mother-to-child HIV transmission at labour and delivery. Socio-cultural and economic factors prevent women from accessing testing at an opportune time during pregnancy. In addition, a lack of adequate infrastructure often prevents timely delivery of interventions to those who access testing at the last minute (i.e., during labour and delivery). In the wake of a paediatric HIV epidemic and the need for lifelong provision of antiretroviral therapy to infected children, a simple strategy for provision of round-the-clock rapid testing and counselling services in the labour rooms may be cost saving to the healthcare systems worldwide.

Editors’ note: Although studies of programmes of point-of-care rapid HIV testing in labour and delivery have been conducted around the world, the need for additional infrastructure resources, such as round-the-clock counsellors and user friendly and accurate rapid tests, has been an impediment to wider implementation. With only 33% of women needing antiretroviral prophylaxis in pregnancy worldwide actually able to access it, innovations are needed to improve coverage. Labour and delivery are not times conducive to reflection on the personal advantages and disadvantages of knowledge of serostatus but two-stage counselling (short prepartum and extended postpartum), attention to privacy and confidentiality, timely confirmation of results to reduce false-positives and false-negatives, and community-based education engaging partners and highlighting the importance of preventing HIV transmission to infants could identify more babies in need of intrapartum and post-exposure prophylaxis and more mothers needing tailored infant feeding counselling in addition to evaluation for antiretroviral treatment, and care and support.

Lazarus R, Struthers H, Violari A. Hopes, fears, knowledge and misunderstandings: responses of HIV-positive mothers to early knowledge of the status of their baby. AIDS Care. 2009;21(3):329-34.

Little is known about how HIV-positive mothers experience and react to knowing the HIV status of their baby as diagnosed by the polymerase chain reaction (PCR) test at 4-6 weeks. This qualitative study drew on interviews with 20 mothers of HIV-negative and 18 mothers of HIV-positive babies after receiving their baby’s PCR results. Thematic analysis combined exploration of themes that appeared significant to the participants and those relevant to health care. Amongst the themes identified were the following: The period before getting the results involved active mental preparation and was emotionally stressful. Most women accepted the results, but some had doubts about their reliability. Mothers of HIV-negative babies were relieved, but mothers of HIV-positive babies were generally very distressed and expressed a sense of responsibility and guilt. Both groups of mothers had similar hopes for the future of their babies, but the timelines of mothers of HIV-positive babies tended to be shorter. Most women experienced significant levels of stress, but were able to call on support networks and use various individual coping mechanisms to manage their stress. Most women were formula feeding their babies, but regretted not being able to breastfeed. Many women had not planned their current baby and most did not intend to have more children, but many of the latter had not taken active steps to prevent further pregnancy. The findings provide pointers to shortcomings in health worker communication and suggest that more effective communication should take account of normative community views and be more closely attuned to the changing needs and experiences of HIV-positive mothers.

Editors’ note: This study in the urban township of Soweto in Johannesburg, South Africa supports the notion that HIV-positive mothers prefer learning their babies’ status early at 4 to 6 weeks rather than waiting for 12 or more months until maternal antibodies disappear. The need for improvement in health care worker communication is evident from the fact that most of the mothers of infected children planned to replacement feed although breastfeeding offers more benefits to HIV-positive infants than risks of re-infection. As well, although most women said this baby had been unplanned and they would not want to have another, health care workers concentrated on condoms as means of reducing risk of transmission to partners, rather than as contraceptives, and some discouraged sterilisation as a more permanent fertility control option. This is a good example of how data collected using qualitative, in-depth interviews guided by a set of open-ended questions posed to end-users can underscore the need for training and enhanced service delivery.

Semprini AE, Hollander LH, Vucetich A, Gilling-Smith C. Infertility treatment for HIV-positive women. Womens Health (Lond Engl). 2008;4(4):369-82.

Thanks to antiretroviral combination therapy, HIV-infected individuals live longer, healthier lives and may wish to have children. Women with HIV can attempt to conceive naturally or through simple self-insemination to minimize the risk of horizontal HIV transmission. Assisted reproduction technology is necessary in couples with infertility, which can either be independent of HIV infection and its treatment or be associated with it. This article summarizes the latest evidence regarding the desire for a child in HIV-positive women and how HIV infection and its treatment may impact female fertility. Current data regarding access to and outcomes of assisted conception programs in HIV-positive women wishing to conceive in both high- and low-income countries are also reviewed.

Editors’ note: This exhaustive review covers the evidence that women living with HIV have similar levels of intentions to be a parent as do other women, that pregnancy itself does not worsen the immunological status of HIV-positive women and is not correlated with disease progression, and that HIV-positive women experience increased tubal infertility and reduced ovarian reserve. Limiting unprotected intercourse to the day of ovulation in women who have been screened and treated for sexually transmitted infections can reduce but not eliminate the risk of horizontal transmission to the male partner. The authors favour low-cost, home-based, simple self-insemination which eliminates the risk of HIV transmission to the uninfected male partner. If after 6 cycles of self-insemination with no conception, fertility investigations should begin. Emphasising that leading professional organisations state that assisted reproductive techniques should not be denied HIV-infected couples, the authors conclude with a section on limiting the risks of HIV transmission associated with in vitro fertilisation – intracytoplasmic sperm injection techniques and highlighting the success of sperm-washing programmes in Europe.

Speizer IS, White JS. The unintended consequences of intended pregnancies: youth, condom use, and HIV transmission in Mozambique. AIDS Educ Prev. 2008;20(6):531-46.

Although unwanted pregnancies can cause social and economic problems for sub-Saharan African youth, the consequences of intended adolescent pregnancies have gone unnoticed. Rarely do studies recognize that youth who desire a pregnancy are less likely to practice safe sex and, therefore, are at greater risk of contracting sexually transmitted infections (STIs), including HIV. This study uses data from the 2003 Mozambique Demographic and Health Survey to explore youth fertility desires and condom use. In multivariate analyses, controlling for other factors associated with condom use, female youth who want to get pregnant soon are significantly less likely (odds ratio: 0.35; 95% confidence interval: 0.22-0.55) to use condoms with non-marital partners than youth who want to delay childbearing. Programs for sexually active youth should recognize the importance of fertility desires as a potential moderator of condom use, even if the woman is at risk of HIV or STI. Recommendations are provided for HIV prevention counselling for youth who want to get pregnant and youth who are ambivalent about a future pregnancy.

Editors’ note: A common reality in many settings in sub-Saharan Africa is that, in the transition to adulthood, pregnancy (or childbirth) is often a precursor to union formation and marriage/cohabitation. HIV prevention programmes should determine which youth have an unmet need for family planning and condoms to prevent unintended pregnancy and sexually transmitted disease and which youth want to get pregnant in the near future. Strategies that the latter group of young women can use to reduce HIV risks include having sex only in the fertile period, discussing HIV risks with a partner, and undertaking HIV testing and counselling with this partner. This broader HIV prevention programme focus, considering the fertility desires of youth, can help reduce their HIV and unintended pregnancy risks.

This article presents the status of rural Bangladeshi adolescent girls’ awareness about reproductive health. Analysis of data revealed that a sizable proportion of adolescent girls had incorrect knowledge or misconceptions about the fertile period, reproduction, sexually transmitted diseases, and HIV. Age, education either of adolescents or their mothers, residence, and exposure to mass media were the significant predictors of adolescent girls’ knowledge about reproductive health. Strong efforts are needed to improve awareness and to clarify misconceptions about reproductive health. Improved access to mass media and education could improve rural Bangladeshi adolescent girls’ awareness about reproductive health.

Editors’ note: Only 7% of the 920 rural adolescent girls, aged 10 to 19 years, participating in this study had correct knowledge about the fertile period and 18 of 20 married adolescents who had given birth in the previous 6 months did not understand why they became pregnant. Only 20% of the girls had heard about sexually transmitted disease and of the 40% who had heard about AIDS, only 22% had correct knowledge about the routes of HIV transmission. These findings underscore the evident need to enhance behaviour change communication with culturally appropriate messages on reproductive health and strengthen access for adolescent girls in Bangladesh to sexual and reproductive health information and services through multiple entry points (school, work, sports, social activities) and settings (home, community, workplace, school or clinic).

Kagaayi J, Gray RH, Brahmbhatt H, Kigozi G, Nalugoda F, Wabwire-Mangen F, Serwadda D, Sewankambo N, Ddungu V, Ssebagala D, Sekasanvu J, Kigozi G, Makumbi F, Kiwanuka N, Lutalo T, Reynolds SJ, Wawer MJ. Survival of Infants Born to HIV-Positive Mothers, by Feeding Modality, in Rakai, Uganda. PLoS ONE. 2008;3(12):e3877.

Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. Kagaayi and colleagues compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda. 182 infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counselling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving antiretroviral therapy. Infant HIV infection was detected by polymerase chain reaction (Roche Amplicor 1.5) during the follow-up visits. Kaplan-Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR) of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%-29%) among the formula-fed compared to 3% (95% CI = 1%-9%) among the breast-fed infants (unadjusted hazard ratio (HR) = 6.1(95% CI = 1.7-21.4, P-value<0.01). There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted HR = 2.8[95%CI = 0.67-11.7, P-value = 0.16]. Formula feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. The authors conclude that these findings suggest that formula feeding should be discouraged in similar African settings.

Editors’ note: This small study in which women self-selected to breastfeed found a striking six-fold increased infant mortality among infants that were fed breast milk substitutes. The excess mortality remained even when infants found to have HIV infection at one month of age were excluded from the analysis. Less than 4% of the households had access to tap water and most mothers did not follow guidelines for sterile preparation and storage of formula, cleansing of utensils, and avoidance of bottle feeds. Strategies for HIV-positive mothers such as prolonged infant prophylaxis or material antiretroviral treatment during lactation need closer consideration.

The KIDS-ART-LINC Collaboration. Low Risk of Death, but Substantial Program Attrition, in Pediatric HIV Treatment Cohorts in Sub-Saharan Africa. J Acquir Immune Defic Syndr. 2008 – see if published 2008;49(5) 521-31.

To date, an estimated 10% of children eligible for antiretroviral treatment receive it, and the frequency of retention in programmes is unknown. The authors evaluated the 2-year risks of death and loss to follow-up of children after antiretroviral treatment initiation in a multicenter study in sub-Saharan Africa. Pooled analysis of routine individual data from 16 participating clinics produced overall Kaplan-Meier estimates of the probabilities of death or loss to follow-up after antiretroviral treatment initiation. Risk factors analysis used Weibull regression, accounting for between-cohort heterogeneity. The median age of 2405 children at antiretroviral treatment initiation was 4.9 years (12%, younger than 12 months), 52% were male, 70% had severe immunodeficiency, and 59% started antiretroviral treatment with a nonnucleoside reverse transcriptase inhibitor. The 2-year risk of death after antiretroviral treatment initiation was 6.9% (95% confidence interval [CI]: 5.9 to 8.1), independently associated with baseline severe anaemia (adjusted hazard ratio [aHR]: 4.10 [CI: 2.36 to 7.13]), immunodeficiency (adjusted aHR: 2.95 [CI: 1.49 to 5.82]), and severe clinical status (adjusted aHR: 3.64 [CI: 1.95 to 6.81]); the 2-year risk of loss to follow-up was 10.3% (CI: 8.9 to 11.9), higher in children with severe clinical status. The authors conclude that, once on treatment, the 2-year risk of death is low but the loss to follow-up risk is substantial. Antiretroviral treatment is still mainly initiated at advanced disease stage in African children, reinforcing the need for early HIV diagnosis, early initiation of antiretroviral treatment, and procedures to increase programme retention.

Editors’ note: Although the 2-year risk of mortality after initiation of antiretroviral treatment was low, 75% of these deaths occurred in the first 6 months of treatment, with baseline HIV stage, nutritional status, and anaemia playing a role. The 10% programme attrition due to loss to follow-up constitutes a serious programme weakness that may reflect unreported death or moving; caregiver illness or death; inability to pay for transport, drugs, or laboratory tests; lack of follow-up procedures for no shows, or other causes. All programmes, whether adult or paediatric, should strive to minimize losses to follow-up by determining the causes and addressing them.

Andia I, Kaida A, Maier M, Guzman D, Emenyonu N, Pepper L, Bangsberg DR, Hogg RS. Highly Active Antiretroviral Therapy and Increased Use of Contraceptives Among HIV-Positive Women During Expanding Access to Antiretroviral Therapy in Mbarara, Uganda. Am J Public Health. 2009; 99(2):340-7.

Andia and colleagues investigated whether the prevalence of contraceptive use among women who are HIV-positive varied according to use of highly active antiretroviral therapy (HAART) in Mbarara, Uganda. They used data from a cross-sectional survey of 484 women who were HIV-positive (18-50 years) and were attending Mbarara University’s HIV clinic, 45% of whom were receiving HAART. Multivariate logistic regression was used to investigate the association between HAART use and contraceptive use. Data were collected between November 2005 and June 2006. Overall, 45% of the women were sexually active in the previous 3 months. Of these, 85% reported using contraceptive methods, with 84% reporting use of barrier contraceptive methods. Women receiving HAART were more than twice as likely to use contraceptive methods (adjusted odds ratio [AOR]=2.64; 95% confidence interval [CI]=1.07, 6.49) and more than 3 times as likely to use barrier contraceptive methods (AOR=3.62; 95% CI=1.54, 8.55) than were women not receiving HAART. The authors conclude that these findings support the need for increased attention to better integration of reproductive health and HIV services for women who are HIV positive.

Editors’ note: The Ugandan women on antiretroviral treatment in this study had been on treatment for a relatively short period (median 15 months) and 62% of them reported being sexually abstinent, possibly as a result of situational abstinence (30% of them were widows) rather than deliberate abstinence. Only 14% wanted more children but improved health status may increase fertility desires, a question that longer follow-up can help answer. In the meantime, this study underscores the importance of ensuring that antiretroviral treatment programmes offer women reproductive health care on site so that they can make informed choices and have the tools to act on them.

Homsy J, Bunnell R, Moore D, King R, Malamba S, Nakityo R, Glidden D, Tappero J, Mermin J. Reproductive intentions and outcomes among women on antiretroviral therapy in rural Uganda: a prospective cohort study. PLoS ONE. 2009;4(1):e4149.

Antiretroviral therapy may influence the biological, social and behavioural determinants of pregnancy in HIV-infected women. However, there are limited longitudinal data on the reproductive intentions and outcomes among women on antiretroviral therapy in Africa. Using a prospective cohort design, Homsy and colleagues analyzed trends in desire for children and predictors of pregnancy among a cohort of 733 HIV-infected women in rural Uganda who initiated antiretroviral therapy between May 2003 and May 2004 and were followed up in their homes until June 2006. Women answered in-depth social and behavioural questionnaires administered every quarter in year 1 after initiating antiretroviral therapy, and every 6 to 12 months thereafter. Use of family planning methods was assessed at 18 and 24 months after starting antiretroviral therapy. The authors tested for non-constant pregnancy incidence by using a shape parameter test from the Weibull distribution. They modelled repeated measurements of all variables related to the women’s desire for children over time using a generalized estimating equation extension to the logistic regression model. Risk factors for pregnancy were examined using Cox proportional hazards model. 711 women eligible for the study were followed-up for a median time of 2.4 years after starting antiretroviral therapy. During this time, less than 7% of women reported wanting more children at any time point yet 120 (16.9%) women experienced 140 pregnancies and pregnancy incidence increased from 3.46 per 100 women-years in the first quarter to 9.5 per 100 women-years at 24 months (p<0.0001). This was paralleled by an increase in the proportion of women reporting sexual activity in the past 3 months, from 24.4% at baseline to 32.5% over 24 months of follow-up (p = 0.001). Only 14% of women used permanent or semi-permanent family planning methods by their second year on ART. In the multivariate model, younger age (HR = 2.71 per 10-year decrease, 95% CI: 2.95-3.78), having a body mass index>18.5 (HR = 1.09, CI:1.01-1.18) and not having used condoms consistently in the last 3 months (HR = 1.79, CI: 1.02-3.13) were independently associated with pregnancy. Women on antiretroviral therapy and their partners should be consistently counselled on the effects of antiretroviral therapy in restoring fertility, and offered regularly free and comprehensive family planning services as part of their standard package of care.

Editors’ note: Again from Uganda (see Andia et al abstract), this home-based AIDS care study documents the gap between not wanting more children and falling pregnant. The incidence of pregnancy increased over follow-up despite the fact that 93% of women repeatedly expressed not wanting or not planning to have more children. Following the study results, counsellors and nurses were retrained and then pro-actively counselled all registered clients on family planning quarterly, delivered hormonal contraceptives at home, and actively referred and followed up women opting for hormonal implants or tubal ligation. This is a good example of knowledge translation into action.

Ciaranello AL, Seage GR 3rd, Freedberg KA, Weinstein MC, Lockman S, Walensky RP. Antiretroviral drugs for preventing mother-to-child transmission of HIV in sub-Saharan Africa: balancing efficacy and infant toxicity. AIDS. 2008;22(17):2359-69.

Antiretroviral drugs can prevent mother-to-child transmission of HIV infection, but in-utero antiretroviral exposure may be associated with neurologic symptoms due to mitochondrial toxicity. Ciaranello and colleagues sought to identify the currently recommended regimen to prevent mother-to-child transmission that optimally balances risks of pediatric HIV infection and neurologic mitochondrial toxicity. Published mother-to-child transmission and mitochondrial toxicity data were used in a decision analytic model of mother-to-child transmission among women in sub-Saharan Africa. The authors investigated the HIV and mitochondrial toxicity risks associated with no antiretroviral prophylaxis and five recommended regimens ranging from single-dose nevirapine to three-drug antiretroviral therapy. Sensitivity analyses varied all parameters, including infant feeding strategy and the disability of mitochondrial toxicity relative to HIV. Provision of no antiretroviral drugs is the least effective and least toxic strategy, with 18-month HIV risk of 30.4% and mitochondrial toxicity risk of 0.2% (breastfed infants). With increasing drug number and duration, HIV risk decreases markedly (to 4.9% with three-drug antiretroviral therapy), but mitochondrial toxicity risk also increases (to 2.2%, also with three-drug antiretroviral therapy). Despite increased toxicity, three-drug antiretroviral therapy minimizes total adverse pediatric outcomes (HIV plus mitochondrial toxicity), unless the highest published risks are true for both HIV and mitochondrial toxicity, or the disability from mitochondrial toxicity exceeds 6.4 times that of HIV infection. The risk of paediatric mitochondrial toxicity from effective regimens to prevent mother-to-child transmission is at least an order of magnitude lower than the risk of HIV infection associated with less-effective regimens. Concern regarding mitochondrial toxicity should not currently limit the use of three-drug antiretroviral therapy to prevent mother-to-child transmission where it is available.

Editors’ note: This modelling showed that protease inhibitor (PI) based 3 drug antiretroviral regimens (ZDV, 3TC, PI) resulted in fewer paediatric infections, slightly more cases of paediatric mitochondrial toxicity, and substantially fewer adverse paediatric outcomes than less toxic but less effective regimens. The true prevalence and severity of infant neurological dysfunction related to mitochondrial toxicity remains unknown. Such toxicity is thought to be due primarily to in utero exposure to NRTI (nucleoside reverse transcriptase inhibitors), however maternal HIV viraemia also appears to be an independent risk factor for foetal mitochondrial dysfunction. Whether there will be next generation effects for the foetuses exposed to NRTI, as was seen for women whose mothers used diethylstilbestrol in the 1950s to prevent threatened abortions and unknowingly placed their daughters at higher risk of vaginal cancer, will not be known for a decade or two.

Six Week Extended-Dose Nevirapine (SWEN) Study Team, Bedri A, Gudetta B, Isehak A, Kumbi S, Lulseged S, Mengistu Y, Bhore AV, Bhosale R, Varadhrajan V, Gupte N, Sastry J, Suryavanshi N, Tripathy S, Mmiro F, Mubiru M, Onyango C, Taylor A, Musoke P, Nakabiito C, Abashawl A, Adamu R, Antelman G, Bollinger RC, Bright P, Chaudhary MA, Coberly J, Guay L, Fowler MG, Gupta A, Hassen E, Jackson JB, Moulton LH, Nayak U, Omer SB, Propper L, Ram M, Rexroad V, Ruff AJ, Shankar A, Zwerski S. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet 2008; 26;372(9635):300-13.

UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR-negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. A total of 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high.

Editors’ note: Science moves quickly in this field. Although the co-principal investigator and several colleagues in India disputed the interpretation of the results of this study, the PEPI study in Malawi now has found possibly even better results with 14 weeks of nevirapine prophylaxis started immediately after birth without a one-week delay. There is no doubt that major efforts should intensify to expand basic mother-to-child transmission prevention programmes beyond the current one-third coverage worldwide. Pending normative guidance, programmes that are already up and running need to consider whether to move now to add extended infant nevirapine prophylaxis when breastfeeding is the safest option that mothers have.

Chung MH, Kiarie JN, Richardson BA, Lehman DA, Overbaugh J, Kinuthia J, Njiri F, John-Stewart GC. Highly active antiretroviral therapy versus zidovudine/nevirapine effects on early breast milk HIV type-1 Rna: a phase II randomized clinical trial. Antivir Ther 2008;13(6):799-807.

Defining the effect of antiretroviral regimens on breast milk HIV type-1 (HIV-1) levels is useful to inform the rational design of strategies to decrease perinatal HIV-1 transmission. Pregnant HIV-1 seropositive women (CD4+ T-cell count >250 and <500 cells/mm3) electing to breastfeed in Nairobi, Kenya were randomized to highly active antiretroviral therapy (HAART; zidovudine [ZDV], lamivudine and nevirapine [NVP]) during pregnancy and 6 months post-partum or to short-course ZDV plus single-dose NVP (ZDV/NVP). Breast milk samples were collected two to three times per week in the first month post-partum. Between November 2003 and April 2006, 444 breast milk samples were collected from 58 randomized women during the first month after delivery. Between 3 and 14 days post-partum, women in the HAART and ZDV/NVP arms had a similar prevalence of undetectable breast milk HIV-1 RNA. From 15 to 28 days post-partum, women in the HAART arm had significantly lower levels of breast milk HIV-1 RNA than women randomized to ZDV/NVP (1.7 log10 copies/ml [limit of detection] versus >2.10 log10 copies/ml, P<0.001). In contrast to breast milk HIV-1 RNA, suppression of plasma HIV-1 RNA during the neonatal period was consistently several log10 greater in the HAART arm compared with the ZDV/NVP arm. HAART resulted in lower breast milk HIV-1 RNA than ZDV/NVP; however, ZDV/NVP yielded comparable breast milk HIV-1 RNA levels in the first 2 weeks post-partum. Breast milk HIV-1 RNA remained suppressed in the ZDV/NVP arm despite increased plasma HIV-1 levels, which might reflect local drug effects or compartmentalization.

Editors’ note: This study revealed the surprising durability of single-dose nevirapine in suppressing early breast milk HIV-1 RNA compared with combination antiretroviral treatment. A larger trial is needed to determine whether 6-month antiretroviral treatment of breastfeeding mothers, who would not be otherwise eligible for treatment under current guidelines, is incrementally effective in reducing breast milk transmission between 3 weeks and 6 months post-partum.

Varga C, Brookes H. Factors Influencing Teen Mothers’ Enrolment and Participation in Prevention of Mother-to-Child HIV Transmission Services in Limpopo Province, South Africa. Qual Health Res. 2008;18(6):786-802.

In this article, Varga and colleagues examine barriers to HIV testing uptake and participation in prevention of mother-to-child HIV transmission services among adolescent mothers aged 15 to 19 years in rural and urban Limpopo Province, South Africa. The authors used the narrative research method involving key informants constructing typical case studies of adolescent experiences with HIV testing and entry into prevention of mother-to-child HIV transmission. Case studies formed the basis of a community-based questionnaire and focus group discussions with adolescent mothers. Client-counsellor dynamics during pre-test counselling were pivotal in determining uptake and participation, and counsellor profile strongly influenced the nature of the interaction. Other factors found to influence adherence to prevention of mother-to-child HIV transmission recommendations included HIV and early premarital pregnancy stigma, fear of a positive test result, and concerns over confidentiality and poor treatment by health care providers. Adolescents described elaborate strategies to avoid HIV disclosure to labour and delivery staff, despite knowing this would mean no antiretroviral therapy for their newborn infants. Theoretical, methodological, and programmatic implications of study findings are also discussed.

Editors’ note: By age 19, 30% of South African adolescent girls have been pregnant. Surveillance data estimate that more than 15% of pregnant adolescents are HIV-positive. The double stigma of pregnancy and HIV infection along with negative attitudes among health care workers poorly prepared to deal with adolescents underpin poor programme uptake. Sufficient training and adequate time to ensure supportive interactions during the initial pre-test counselling contact is an obvious first step to healthier outcomes for both adolescent mothers and their infants.

In developing countries, mother-to-child transmission of HIV is responsible for 5-10% of all new HIV infections. HIV positive mothers can transmit HIV to their babies during pregnancy, childbirth and breast-feeding. Anti-retroviral drugs are effective in reducing the risk of mother-to-child transmission of HIV. The main focus of this study was to describe mothers’ attitudes towards using services for preventing mother-to-child transmission of HIV. A non-experimental, descriptive design with a survey approach was used. The study was conducted at one hospital in Bulawayo, Zimbabwe that offers both prenatal clinic and maternity, including prevention of mother-to-child transmission, services. Fifty pregnant women, who attended prenatal clinics in Bulawayo and who booked to deliver their babies in the hospital’s maternity section, were interviewed. A structured interview survey was used to collect data. The interviewed women required more knowledge about preventing mother-to-child transmission of HIV. Many pregnant women would not use the services available for the prevention of mother-to-child transmission of HIV, for personal, financial and cultural reasons. However, the most important barriers preventing pregnant women from using free prevention of mother-to-child transmission services were structural ones. Only pregnant women who attended prenatal clinics and delivered their babies in hospital could access these services. Prenatal and delivery services might be beyond the financial reach of many Zimbabwean women, making prevention of mother-to-child transmission services inaccessible to them. Free infant formula could not be accessed at hospitals and clinics because of transport costs.

Editors’ note: This small study in one site highlights practical constraints that must be overcome to achieve universal access to prevention of mother-to-child transmission. Although HIV testing and counselling, antiretroviral prophylaxis, and counselling and support for safe infant feeding were available free of charge, basic pre-natal, delivery, and post-natal services were not. When women cannot access these because of transport or financial constraints, prevention of mother-to-child transmission doesn’t even make it to the table.

Bollen and colleagues aimed to evaluate the association between maternal herpes simplex virus type 2 seropositivity and genital herpes simplex virus type 2 shedding with perinatal HIV transmission. Women who participated in a 1996-1997 perinatal HIV transmission prevention trial in Thailand were evaluated. In this non-breastfeeding population, women were randomized to zidovudine or placebo from 36 weeks gestation through delivery; maternal plasma and cervicovaginal HIV viral load and infant HIV status were determined for the original study. Stored maternal plasma and cervicovaginal samples were tested for herpes simplex virus type 2 antibodies by enzyme-linked immunoassay and for herpes simplex virus type 2 DNA by real-time PCR, respectively. Among 307 HIV-positive women with available samples, 228 (74.3%) were herpes simplex virus type 2 seropositive and 24 (7.8%) were shedding herpes simplex virus type 2. Herpes simplex virus type 2 seropositivity was associated with overall perinatal HIV transmission [adjusted odds ratio, 2.6; 95% confidence interval, 1.0-6.7)], and herpes simplex virus type 2 shedding was associated with intrapartum transmission (adjusted odds ratio, 2.9; 95% confidence interval, 1.0-8.5) independent of plasma and cervicovaginal HIV viral load, and zidovudine treatment. Median plasma HIV viral load was higher among herpes simplex virus type 2 shedders (4.2 vs. 4.1 log(10)copies/ml; P = 0.05), and more shedders had quantifiable levels of HIV in cervicovaginal samples, compared with women not shedding herpes simplex virus type 2 (62.5 vs. 34.3%; P = 0.005). The authors found an increased risk of perinatal HIV transmission among herpes simplex virus type 2 seropositive women and an increased risk of intrapartum HIV transmission among women shedding herpes simplex virus type 2. These novel findings suggest that interventions to control herpes simplex virus type 2 infection could further reduce perinatal HIV transmission.

Editors’ note: Co-infected women had higher HIV plasma viral loads than did women without herpes simplex virus-2 (HSV-2) in this study which may explain why women with HSV-2 were more likely to transmit to their infants. If these findings are replicated among women receiving currently recommended drugs for prophylaxis of mother-to-child transmission, further evaluation is warranted of adding suppressive treatment for HSV-2 to help prevent mother-to-child transmission. Acyclovir, a drug that is well tolerated in pregnancy, is off patent and cheap.