HIV This Week

Sebert Kuhlmann AK, Kraft JM, Galavotti C, Creek TL, Mooki M, Ntumy R. Radio role models for the prevention of mother-to-child transmission of HIV and HIV testing among pregnant women in Botswana. Health Promot Int. 2008 Apr 11 [Epub ahead of print]

Although Botswana supports a program for the prevention of mother-to-child-transmission of HIV (PMTCT), many women initially did not take advantage of the program. Using data from a 2003 survey of 504 pregnant and post-partum women, Sebert Kuhlmann and his colleagues assessed associations between exposure to a long-running radio serial drama that encourages use of the PMTCT program and HIV testing during pregnancy. Controlling for demographic, pregnancy and other variables, women who spontaneously named a PMTCT character in the serial drama as their favourite character were nearly twice as likely to test for HIV during pregnancy as those who did not. Additionally, multiparity, knowing a pregnant woman taking AZT, having a partner who tested, higher education and PMTCT knowledge were associated with HIV testing during pregnancy. Identification with characters in the radio serial drama is associated with testing during pregnancy. Coupled with other supporting elements, serial dramas could contribute to HIV prevention, treatment and care initiatives.

Editors’ note: This programme went further than public service announcements and counselling sessions to raise awareness of PMTCT services. It used two fundamental principles: modelling (showing people how to change) and reinforcement (supporting their efforts to change and to maintain healthy behaviours). The radio drama was the modelling component and may have helped some women to see HIV testing in pregnancy as a good choice supported by social norms. It is interesting to speculate whether this programme paved the way for broad acceptance of the introduction of a routine offer of antenatal testing in 2004.

Wringe A, Isingo R, Urassa M, Maiseli G, Manyalla R, Changalucha J, Mngara J, Kalluvya S, Zaba B. Uptake of HIV voluntary counselling and testing services in rural Tanzania: implications for effective HIV prevention and equitable access to treatment. Trop Med Int Health. 2008;13(3):319-27.

Wringe and colleagues aimed to describe the associations between socio-demographic, behavioural and clinical characteristics and the use of HIV voluntary counselling and testing (VCT) services among residents in a rural ward in Tanzania. Eight thousand nine hundred and seventy participants from a community-based cohort were interviewed, provided blood for research HIV testing, and were offered VCT. Univariate and multivariate logistic regression was used to identify socio-demographic, clinical, and behavioural factors associated with VCT use. Although 31% (1246/3980) of men and 24% (1195/4990) of women expressed an interest in the service, only 12% of men and 7% of women subsequently completed VCT. Socio-demographic factors, such as marital status, area of residence, religion and ethnicity influenced VCT completion among males and females in different ways, while self-perceived risk of HIV, prior knowledge of VCT, and sex with a high-risk partner emerged as important predictors of VCT completion among both sexes. Among males only, those infected with HIV for 5 years or less tended to self-select for VCT compared to HIV-negatives (adjusted odds ratio = 1.43; 95% CI: 0.99-2.14). This contributed to a higher proportion of HIV-positive males knowing their status compared to HIV-positive females.  In this setting, a disproportionate number of HIV-positive women are failing to learn their status, which has implications for equitable access to onward referral for care and treatment services. Evidence that some high-risk behaviours may prompt VCT use is encouraging, although further interventions are required to improve knowledge about HIV risk and the benefits of VCT. Targeted interventions are also needed to promote VCT uptake among married women and rural residents.

Editors´note: Both the proportion of people interested in learning their HIV serostatus and the proportion of people who actually got tested are very low for a country with a sizeable HIV epidemic. It is likely that fear of stigma and discrimination had remained an important barrier to HIV testing during this study, since the Tanzanian government had already announced on radio and in newspapers that it intended to start providing free antiretroviral treatment though major hospitals.

Brahmbhatt H, Sullivan D, Kigozi G, Askin F, Wabwire-Mangenm F, Serwadda D, Sewankambo N, Wawer M, Gray R. Association of HIV and Malaria With Mother-to-Child Transmission, Birth Outcomes, and Child Mortality. J Acquir Immune Defic Syndr. 2008;47(4):472-476.

Brahmbhatt and colleagues set out to assess the impact of HIV and malaria coinfection on mother-to-child HIV transmission (MTCT) and adverse birth outcomes. One hundred nine HIV-positive mother-infant pairs with a malaria diagnosis were identified in a community cohort and followed up postpartum. Maternal malaria was diagnosed by a rapid immunochromatographic test on sera and histopathologic examination of placenta. Infant HIV was diagnosed within 6 weeks of birth using polymerase chain reaction (PCR) to capture in-utero and intrapartum HIV transmission. Log binomial models were used to assess the relative risk of MTCT, low birth weight, and preterm birth associated with malaria. Approximately 17.4% of infants were HIV positive at or around birth, and the prevalence of serologic and placental malaria were 31% and 32%, respectively.  HIV-positive mothers with serological immunochromatographic test malaria were significantly more likely to have low-birth-weight infants, and low-birth-weight infants had significantly higher risk of MTCT compared with infants of normal birth weight. Although placental and serologic immunochromatographic test malaria were significantly associated with MTCT, after adjusting for maternal HIV viral load, the risk of MTCT was significantly increased only for mothers coinfected with placental malaria (relative risk [RR] = 7.9, P = 0.025). The authors conclude that placental malaria increases the risk of MTCT after adjustment for viral load. Programmes should focus on enhanced malaria prevention during pregnancy to decrease the risk of adverse birth outcomes and MTCT.

Editors´note: Coinfection with malaria and HIV during pregnancy is known to have adverse consequences for morbidity and mortality of infants. Placental malaria is more prevalent in HIV-positive mothers than HIV-negative mothers. In this study using highly sensitive diagnostic methods, placental malaria in pregnant women with HIV infection increased the risk of mother-to-child HIV transmission, irrespective of maternal viral load. This suggests that prevention of placental malaria in pregnancy is important to prevent HIV transmission to infants.

Ryan M, Griffin S, Chitah B, Walker AS, Mulenga V, Kalolo D, Hawkins N, Merry C, Barry MG, Chintu C, Sculpher MJ, Gibb DM. The cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia. AIDS. 2008;22(6):749-57.

Ryan and colleagues aimed to assess the cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia, as implementation at the local health centre level has yet to be undertaken in many resource-limited countries despite recommendations in recent updated World Health Organization (WHO) guidelines. A probabilistic decision analytical model of HIV progression in children based on the CD4 cell percentage (CD4%) was populated with data from the placebo-controlled Children with HIV Antibiotic Prophylaxis trial that had reported a 43% reduction in mortality with cotrimoxazole prophylaxis in HIV-infected children aged 1-14 years. Unit costs (US$ in 2006) were measured at University Teaching Hospital, Lusaka. Cost-effectiveness, expressed as cost per life-year saved; cost per quality adjusted life-year saved; and cost per disability adjusted life-year averted, was calculated across a number of different scenarios at tertiary and primary healthcare centres. Cotrimoxazole prophylaxis was associated with incremental cost-effectiveness ratios of US$72 per life-year saved, US$94 per quality adjusted life-year saved, and US$53 per disability adjusted life-year averted, i.e. substantially less than a cost-effectiveness threshold of US$1019 per outcome (gross domestic product per capita, Zambia 2006). Incremental cost-effectiveness ratios of US$5 or less per outcome demonstrate that cotrimoxazole prophylaxis is even more cost-effective at the local healthcare level. The intervention remained cost-effective in all sensitivity analyses including routine haematological and CD4% monitoring, varying starting age, AIDS status, cotrimoxazole formulation, efficacy duration, and discount rates. Cotrimoxazole prophylaxis in HIV-infected children is an inexpensive low technology intervention that is highly cost-effective in Zambia, strongly supporting the adoption of WHO guidelines into essential healthcare packages in low-income countries.

Editors´note: Along with other factors, cost-effectiveness analyses can inform decision-making on competing priorities. In this case, highly cost-effective cotrimoxazole in children with HIV infection is life-saving, simple, well–tolerated and inexpensive. It is a key element of pre-antiretroviral treatment care and part of the HIV chronic care package. The gap between World Health Organisation guidance and actual practice at the country level in sub-Saharan Africa needs to close rapidly for all children with HIV infection.

Dandona L, Kumar SG, Ramesh YK, Rao MC, Marseille E, Kahn JG, Dandona R. BMC Health Serv Res. 2008;8:26. Outputs, cost and efficiency of public sector centres for prevention of mother to child transmission of HIV in Andhra Pradesh, India.

Prevention of mother to child transmission is an important part of the effort to control HIV. PMTCT services are mostly provided at public sector government hospitals in India. Systematic data on the cost and efficiency of providing prevention of mother-to-child transmission services in India are not available readily for further planning. Cost and output data were collected at 16 sampled prevention of mother to child transmission centres in the south Indian state of Andhra Pradesh using standardized methods. The services provided were analysed, and the relation of unit cost of services with scale was assessed. In the 2005-2006 fiscal year, 125,073 pregnant women received prevention of mother to child transmission services at the 16 centres (range 2,939 to 20,896, median 5,679). The overall HIV positive rate among those tested was 1.67%. Of the total economic cost, the major components were personnel (47.3%) and recurrent goods (31.7%). For the 16 prevention of mother-to-child transmission centres, the average economic cost per post-HIV-test counselled pregnant woman was Indian Rupees (INR) 98.9 (US$ 2.23), ranging 2.7-fold from INR 71.4 (US$ 1.61) to INR 189.9 (US$ 4.29). The economic cost per mother-neonate pair who received nevirapine had a higher variation, ranging 41-fold for the 16 centres from INR 4,354 (US$ 98 ) to INR 179,175 (US$ 4,047), average INR 10,210 (US$ 231), with very high unit cost at some centres where HIV prevalence among pregnant women and the total volume of services were both low. Scale had a significant inverse relation with both of the unit costs, per post-HIV-test counselled pregnant woman and per mother-neonate pair who received nevirapine. In addition, HIV prevalence among pregnant women had a significant inverse relation with unit cost per mother-neonate pair who received nevirapine. Although the variation between prevention of mother-to-child transmission centres for unit cost per post-HIV-test counselled pregnant woman was modest that per mother-neonate pair receiving nevirapine was over 40-fold. The extremely high unit cost for each mother-neonate pair receiving nevirapine at some centres suggests that the new approach of combining prevention of mother to child transmission services with voluntary counselling and testing services that has recently been started in India could potentially offer better efficiency.

Editors’ note: An inverse relationship between unit cost and scale makes common sense. The piece that is missing in the equation is how many pregnancies in these 16 prevention of mother-to-child transmission centres were unplanned and unwanted. Integrating these services with voluntary counselling and testing services makes more than economical sense if fertility counselling is offered to all men and women testing HIV-positive.

Keiser O, Orrell C, Egger M, Wood R, Brinkhof MW, Furrer H, van Cutsem G, Ledergerber B, Boulle A; for the Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases to Evaluate AIDS in Southern Africa (IeDEA-SA). Public-Health and Individual Approaches to Antiretroviral Therapy: Township South Africa and Switzerland Compared. PLoS Med. 2008;5(7):e148.

The provision of highly active antiretroviral therapy in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. Keiser and colleagues compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting highly active antiretroviral therapy in South Africa and Switzerland. The authors analysed data from the Swiss HIV Cohort Study and two highly active antiretroviral therapy programmes in townships of Cape Town, South Africa. They included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded injecting drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4(+) T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of highly active antiretroviral therapy: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. Compared to the highly individualised approach in Switzerland, programmatic highly active antiretroviral therapy in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to highly active antiretroviral therapy and improve the prognosis of patients who start highly active antiretroviral therapy with advanced disease.

Editors´note: It is reassuring that the public health treatment approach in South Africa is as effective virologically as is the individualized approach of Switzerland: 96% of patients in both South Africa and Switzerland suppressed viral load to less than 500 copies/ml within a year. Although similar percentages developed viral rebound within two years, there were differences in mortality primarily due to the much lower CD4 count in South Africans (median 80) compared to Swiss (median of 204) at baseline. Know your status campaigns that provide social support for HIV testing and counselling would permit earlier initiation of treatment and reduce early mortality in South Africans on treatment. On the Swiss side, Switzerland could well consider simplifying its 36 first-line regimens.

Youngpairoj AS, Masciotra S, Garrido C, Zahonero N, de Mendoza C, García-Lerma JG. HIV-1 drug resistance genotyping from dried blood spots stored for 1 year at 4 degrees Celsius. J Antimicrob Chemother. 2008 Mar 15 [Epub ahead of print]

Dried blood spots are an attractive alternative to plasma for HIV-1 drug resistance testing in resource-limited settings. Youngpairoj and colleagues recently showed that HIV-1 can be efficiently genotyped from dried blood spots stored at -20 degrees C for prolonged periods (0.5-4 years). Here, the authors evaluated the efficiency of genotyping from dried blood spots stored at 4 degrees C for 1 year. A total of 40 dried blood spots were prepared from residual diagnostic specimens collected from HIV subtype B-infected persons and were stored with desiccant at 4 degrees C. Total nucleic acids were extracted after 1 year using a modification of the Nuclisens assay. Resistance testing was performed using the ViroSeq HIV-1 assay and an in-house nested Reverse Transciptase PCR method validated for HIV-1 subtype B that amplifies a smaller (1 kb) pol fragment. Using the ViroSeq assay, only 23 of the 40 (57.5%) dried blood spot specimens were successfully genotyped; 22 of these specimens had plasma viraemia >10 000 RNA copies/mL. When the specimens were tested using the in-house assay, 38 of the 40 dried blood spots (95%) were successfully genotyped. Overall, resistance genotypes generated from the dried blood spots and plasma were highly concordant. The authors show that drug resistance genotyping from dried blood spots stored at 4 degrees C with desiccant is highly efficient but requires the amplification of small pol fragments and the use of an in-house nested PCR protocol with quality-controlled reagents. These findings suggest that 4 degrees Celsius may represent a suitable temperature for long-term storage of dried blood spots.

Editors´note: Dried blood spots are easy to transport, can be stored for long periods, and can be used now for a variety of micro-level diagnostic tests. The HIV drug resistance genotyping test described here would require product development to move it from an “in-house” modified test to a standardized procedure that could be used in national resistance surveillance.

Kumwenda NI, Hoover DR, Mofenson LM, Thigpen MC, Kafulafula G, Li Q, Mipando L, Nkanaunena K, Mebrahtu T, Bulterys M, Fowler MG, Taha TE. Extended Antiretroviral Prophylaxis to Reduce Breast-Milk HIV-1 Transmission. N Engl J Med. 2008 Jun 4. Epub ahead of print.

Photo credit: WHO/UNAIDS/L.Gubb

Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, Kumwenda and colleagues assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. In conclusion, extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants.

Editors´note: The protective efficacy of both extended prophylaxis regimens was more than 60% at 14 weeks, significantly better that a control regimen of single dose nevirapine and 1 week of zidovudine. However, there were significantly more infants with serious adverse events in the dual extended prophylaxis group than in either of the other groups and HIV infection rates were similar for all three groups from age 14 weeks to 9 months, once drug was withdrawn. Based on these findings, a practical approach would be to consider prolonging the extended nevirapine regimen for the duration of breast-feeding. Clearly, serious study is now needed of the risks and benefits for mothers and babies of uninterrupted maternal antiretroviral therapy in pregnancy and beyond, irrespective of CD4 count, for HIV-positive women in settings in which breastfeeding is the safest option for infants.

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Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Mwiya M, Kasonde P, Scott N, Vwalika C, Walter J, Bulterys M, Tsai WY, Thea DM; the Zambia Exclusive Breastfeeding Study. Effects of Early, Abrupt Weaning for HIV-free Survival of Children in Zambia. N Engl J Med. 2008 Jun 4. Epub ahead of print.

In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. Kuhn and colleagues conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. The authors enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counselling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P=0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P=0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P=0.007). In conclusion, early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants.

Editors´note: The fact that only two-thirds of the women assigned to early abrupt weaning at 4 months did so, despite provision of free formula, complementary food, and home counselling visits, affected the intention-to-treat analysis. Even had the trial found an HIV-free survival advantage at 24 months for early abrupt weaning, this practice might not have been acceptable in this population where breastfeeding into the second year of life is the norm. WHO currently advises exclusive breastfeeding to 6 months of age and continued breastfeeding with complementary foods after 6 months if replacement feeding is still not acceptable, feasible, affordable, sustainable, and safe (AFASS). Most importantly, this trial demonstrated clear harm for infants who were already HIV-infected at 4 months and who were abruptly weaned. Now, it is no longer ethical to design trials in which HIV-exposed infants are randomly assigned to infant feeding interventions without knowledge of their HIV status.

Pai NP, Barick R, Tulsky JP, Shivkumar PV, Cohan D, Kalantri S, Pai M, Klein MB, Chhabra S. Impact of round-the-clock, rapid oral fluid HIV testing of women in labor in rural India. PLoS Med. 2008;5(5):e92.

Testing pregnant women for HIV at the time of labour and delivery is the last opportunity for prevention of mother-to-child HIV transmission measures, particularly in settings where women do not receive adequate antenatal care. However, HIV testing and counselling of pregnant women in labour is a challenge, especially in resource-constrained settings. In India, many rural women present for delivery without any prior antenatal care. Those who do get antenatal care are not always tested for HIV, because of deficiencies in the provision of HIV testing and counselling services. In this context, we investigated the impact of introducing round-the-clock, rapid, point-of-care HIV testing and counselling in a busy labour ward at a tertiary care hospital in rural India. After they provided written informed consent, women admitted to the labour ward of a rural teaching hospital in India were offered two rapid tests on oral fluid and finger-stick specimens (OraQuick Rapid HIV-1/HIV-2 tests, OraSure Technologies). Simultaneously, venous blood was drawn for conventional HIV ELISA testing. Western blot tests were performed for confirmatory testing if women were positive by both rapid tests and dual ELISA, or where test results were discordant. Round-the-clock (24 h, 7 d/wk) abbreviated prepartum and extended postpartum counselling sessions were offered as part of the testing strategy. HIV-positive women were administered prevention of mother-to-child HIV transmission interventions. Of 1,252 eligible women (age range 18 y to 38 y) approached for consent over a 9 month period in 2006, 1,222 (98%) accepted HIV testing in the labour ward. Of these, 1,003 (82%) women presented with either no reports or incomplete reports of prior HIV testing results at the time of admission to the labour ward. Of 1,222 women, 15 were diagnosed as HIV-positive (on the basis of two rapid tests, dual ELISA and Western blot), yielding a seroprevalence of 1.23% (95% confidence interval [CI] 0.61%-1.8%). Of the 15 HIV test-positive women, four (27%) had presented with reported HIV status, and 11 (73%) new cases of HIV infection were detected due to rapid testing in the labour room. Thus, 11 HIV-positive women received prevention of mother-to-child transmission interventions on account of round-the-clock rapid HIV testing and counselling in the labour room. While both OraQuick tests (oral and finger-stick) were 100% specific, one false-negative result was documented (with both oral fluid and finger-stick specimens). Of the 15 HIV-infected women who delivered, 13 infants were HIV seronegative at birth and at 1 and 4 mo after delivery; two HIV-positive infants died within a month of delivery. In a busy rural labour ward setting in India, Pai and colleagues demonstrated that it is feasible to introduce a program of round-the-clock rapid HIV testing, including prepartum and extended postpartum counselling sessions. Their data suggest that the availability of round-the-clock rapid HIV testing resulted in successful documentation of HIV serostatus in a large proportion (82%) of rural women who were unaware of their HIV status when admitted to the labour room. In addition, 11 (73%) of a total of 15 HIV-positive women received prevention of mother-to-child transmission interventions because of round-the-clock rapid testing in the labour ward. These findings are relevant for prevention of mother-to-child transmission programs in developing countries.

Editors´note: Despite the fact that labour is not an ideal time to make a decision about learning one’s serostatus, offering HIV testing during labour is the last chance for women who have had no antenatal care or were not given the opportunity to be tested during pregnancy. Acceptance was high in this study, with HIV prevalence of 1.23% mirroring the 1% anticipated in recent antenatal sentinel surveillance. Studies of cost-effectiveness may be needed to convince policy makers in some resource-constrained settings that this “catch up” approach for women of unknown HIV status has merit.

Kantarci S, Koulinska IN, Aboud S, Fawzi WW, Villamor E. Subclinical Mastitis, Cell-Associated HIV-1 Shedding in Breast Milk, and Breast-Feeding Transmission of HIV-1. J Acquir Immune Defic Syndr. 2007; 46(5):651-654.

Mastitis has been identified as a risk factor for mother-to-child transmission of HIV-1 through breast-feeding. It is unclear whether this association is mediated by increased cell-free virus versus cell-associated virus HIV shedding in breast milk. Kantarci and colleagues examined the risk of mother-to-child transmission associated with subclinical mastitis and the relation between mastitis and cell-free virus or cell-associated virus shedding in breast milk. Fifty-nine women who transmitted HIV through breast-feeding (cases) were individually matched to 59 non-transmitting controls nested in a cohort from Tanzania. For each case, the authors selected a milk specimen obtained before the infant’s first positive test to quantify sodium and potassium and measure cell-free virus and cell-associated virus concentrations. Controls were matched on the child’s age at the time of sample collection. Women with a breast milk sodium/potassium ratio suggestive of mastitis (>1.0) had an 11-fold greater odds of transmission (95% confidence interval [CI]: 1.2 to 98.1), compared to women with a sodium/potassium ratio </=0.6, after adjusting for maternal CD4 cell count and vitamin A supplementation. Although mastitis was positively related to both cell-free virus and cell-associated virus shedding in breast milk, only the association with the latter was strong and statistically significant. In conclusion, increased cell-associated HIV-1 shedding in breast milk could mediate the association between mastitis and mother-to-child transmission.

Editors’ note: Simpler methods to diagnose sub-clinical mastitis, studies to determine when it is safe to resume breast-feeding from the affected breast, and the results of current trials underway assessing the prevention efficacy of antiretroviral treatment provided to HIV-positive lactating women and/or their breastfeeding infants are needed for informed policy guidance.

In April 2007, UNAIDS released Securing the future-advocating for children, a call for the global community to recognize that “children still remain largely absent from national and international political responses to the AIDS pandemic”. Most efforts to date to protect children from HIV have focused on prevention of mother-to-child transmission programs. Though expanding prevention of mother-to-child transmission programs, particularly in sub-Saharan Africa, are crucial, even widespread prevention of mother-to-child transmission programs would still be grossly inadequate for achieving the goal of protecting children from HIV. The global community needs to fundamentally reframe its approach to HIV prevention to fully address the health of families; otherwise the future for at-risk children is likely to remain bleak. After identifying challenges with current approaches, Heymann and colleagues review recent research that provides insights into ways prevention programs may be adapted to better protect families and children from the devastating consequences of HIV. Only by protecting families from HIV will we be able to achieve the goal of an HIV-free generation.

Editors’ note: HIV prevention among partners is key to preventing children becoming infected or being orphaned due to HIV. Couples have a joint incentive to remain HIV-free, to identify HIV infection in either partner early to prevent onward transmission and access treatment, and to make fertility plans together.

Kuhn L, Sinkala M, Kankasa C, Semrau K, Kasonde P, Scott N, Mwiya M, Vwalika C,Walter J, Tsai WY, Aldrovandi GM, Thea DM. High Uptake of Exclusive Breastfeeding and Reduced Early Post-Natal HIV Transmission. PLoS ONE. 2007; 2(12):e1363.

Photo credit: UNAIDS/ L.Alyanak

Empirical data showing the clear benefits of exclusive breastfeeding for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. Kuhn and colleagues conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that exclusive breastfeeding is associated with a lower risk of postnatal HIV transmission than non-exclusive breastfeeding. As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by polymerase chain reaction. Detailed measurements of actual feeding behaviours were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of exclusive breastfeeding was high with 84% of women reporting exclusive breastfeeding cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among exclusively breastfed infants (0.040 95% CI: 0.024-0.055) than among non-exclusively breastfed infants (0.102 95% CI: 0.047-0.157); time-dependent Relative Hazard (RH) of transmission due to non-exclusive breastfeeding = 3.48 (95% CI: 1.71-7.08). There were no significant differences in the severity of disease between exclusively breastfeeding and non-exclusively breastfeeding mothers and the association remained significant (RH = 2.68 95% CI: 1.28-5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. In conclusion, non-exclusive breastfeeding more than doubles the risk of early postnatal HIV transmission. Programs to support exclusive breastfeeding should be expanded universally in low-resource settings. Exclusive breastfeeding is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children’s lives. TRIAL REGISTRATION: ClinicalTrials.gov NCT00310726.

Editors’ note: Exclusive breastfeeding for at least 6 months when the AFASS criteria (acceptable, feasible, affordable, sustainable, and safe) are not met balances the protective infant survival benefits of breastfeeding against the low, sustained risk of HIV acquisition. Relaxing treatment guidelines to provide antiretroviral drugs to lactating mothers with CD4 counts under 350 cells already makes imminent sense now, but several clinical trials assessing this and infant prophylaxis during breastfeeding, have yet to report.

Intrapartum and neonatal single-dose nevirapine are essential components of perinatal HIV prevention in resource-constrained settings, but can induce resistance to other non-nucleoside reverse transcriptase inhibitor drugs. Chi and colleagues aimed to investigate whether this complication would be reduced with a single peripartum intervention of tenofovir and emtricitabine. The authors randomly assigned 400 pregnant women living with HIV who sought care at two public-sector primary health facilities in Lusaka, Zambia. One was excluded, 200 were assigned to receive a single oral dose of 300 mg tenofovir disoproxil fumarate with 200 mg emtricitabine under direct observation, and 199 to receive no study drug. Short-course zidovudine and intrapartum nevirapine were offered to all of the participant women living with HIV, according to the local standard of care. Women who met national criteria for antiretroviral therapy were referred for care and not enrolled. The primary study outcome was resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery. The authors used standard population sequencing to determine HIV genotypes and analyzed data as per protocol. Of the 200 women who were randomly assigned to the intervention, 14 were lost to follow-up or withdrew from the study, two did not take study drug according to protocol, and one specimen was lost; 23 of 199 controls were lost to follow-up or withdrew from the study, and three specimens were lost. Women given the intervention were 53% less likely than controls to have a mutation that conferred resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery (20/173 [12%] vs. 41/166 [25%]; risk ratio [RR] 0.47, 95% CI 0.29-0.76). The authors noted postpartum anaemia, the most common serious adverse event in mothers, in four women in each group. 20 of 198 (10%) infants in the intervention group and 23 of 199 (12%) controls had a serious adverse event, mostly due to septicaemia (n=22) or pneumonia (n=8); these events did not differ between groups, and none were judged to be caused by the study intervention. The authors’ interpretation of the results was that a single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; and therefore this treatment should be considered as an adjuvant to intrapartum nevirapine.

Editors’ note: Although there was no difference in rates of perinatal HIV transmission, adding a single dose of tenofovir (TDF) and emtricitabine (FTC) significantly reduced the risk of resistance from single dose nevirapine. As cited in Lockman et al (HIV This Week Issue #25), women who started antiretroviral treatment within 6 months of receiving a single dose of nevirapine are at risk for virological and clinical treatment failure because of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. Since both nevirapine and efavirenz are common NNRTI components of first line therapy and options for second-line treatment are limited, addition of single dose TDF-FTC makes a lot of sense for the mother’s health.

Bezner Kerr R, Dakishoni L, Shumba L, Msachi R, Chirwa M. “We Grandmothers Know Plenty”: Breastfeeding, complementary feeding and the multifaceted role of grandmothers in Malawi. Soc Sci Med. 2008;66(5):1095-105.

This paper has two purposes: first of all, Bezner Kerr and colleagues examine grandmothers’ role and views of child feeding practices in northern Malawi, and their influence on younger women’s practices. Secondly, the authors consider the implications of these findings for health promotion activities and models of health education. Data were collected from semi-structured interviews, focus groups, and a participatory workshop. Findings demonstrate that, to address child feeding practices which have an effect on nutrition, attention must be paid to the broader context that influences child nutrition, including extended family relations. Paternal grandmothers have a powerful and multifaceted role within the extended family in northern Malawi, both in terms of childcare and in other arenas such as agricultural practices and marital relations. Grandmothers often differ in their ideas about early child feeding from conventional Western medicine. Some practices have existed in the area at least since colonial times, and have strong cultural significance. Despite the important integrated role that older women have within households and communities in this part of Malawi, hospital personnel often have disparaging and paternalistic attitudes towards ‘grannies’ and their knowledge. Health education rarely involves grandmothers, and even if they are involved, their perspectives are not taken into consideration. Hospital staff often reject grandmother knowledge as part of a broader modernization paradigm which views ‘traditional knowledge’ as backward. Grandmothers view current child health conditions within a broader context of changing livelihood conditions and a high prevalence of HIV. The paper concludes by discussing the challenges of involving grandmothers in health education, and the difficulties of incorporating local knowledge into a medical system that largely rejects it.

Editors’ note: Top-down approaches to change feeding practices, which do not take into account the views of key decision-makers or gate-keepers, in this case paternal grandmothers, are bound to face resistance. These women have power and influence over their daughter-in-laws, who are typically the focus of health education about infant feeding, and are experiencing themselves added care giving burdens as a result of high HIV prevalence. Establishing relationships of respect between health personnel and grandmothers who are central figures in agricultural production, social knowledge, and child feeding decisions is the first step. Actively engaging grandmothers in nutrition education can make it possible for young women to exclusively breastfeed, as recommended for infant well-being.

Shapiro RL, Lockman S, Kim S, Smeaton L, Rahkola JT, Thior I, Wester C, Moffat C, Arimi P, Ndase P, Asmelash A, Stevens L, Montano M, Makhema J, Essex M, Janoff EN. Infant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and HIV-uninfected women in Botswana. J Infect Dis 2007; 196:562-9.

Infants of human immunodeficiency virus (HIV)-positive women have high mortality, but the immunologic integrity and protection afforded by the breast milk of HIV-positive women is unknown. Shapiro and colleagues determined morbidity and mortality by 24 months among breast-fed infants of 588 HIV-positive and 137 HIV-negative women followed-up in a clinical trial in Botswana. A matched case-control study compared clinical, behavioral, and breast milk immunologic parameters among 120 HIV-positive women by infant outcome. Breast milk factors were also compared between HIV-positive and HIV-negative women. Twenty-four-month mortality was 29.5% among HIV-positive infants, 6.7% among HIV-exposed uninfected infants, and 1.6% among HIV-unexposed infants. No differences were detected in breast milk immunologic profiles of HIV-positive women whose infants were either ill or well. Discontinuation of breast-feeding was the strongest predictor of illness (P<.001). Levels in breast milk of pathogen-specific immunoglobulin (Ig) G and IgA to Haemophilus influenzae, Campylobacter jejuni, Helicobacter pylori, Streptococcus pneumoniae, and innate immune factors were not lower among HIV-positive women than among HIV-negative women. Mortality was higher among HIV-positive and HIV-exposed infants than among HIV-unexposed infants. However, the immunologic profiles of breast milk among HIV-positive women were intact, and discontinuation of breast-feeding was the primary risk for infant morbidity. Thus, the breast milk of HIV-positive women may confer protection against common infant pathogens.

Editors’ note: This first analysis comparing breast milk immunological profiles among HIV-positive and HIV-negative women did not detect in any differences in immunoglobin levels or other immune factors. Current recommendations are for exclusive breastfeeding by mothers with HIV infection, when breast-milk substitutes are unsafe or not feasible, and early weaning around 6 months of age. In this study, infants exposed to HIV were weaned at 5 to 6 months of age, whereas 9 months was the average for the HIV-unexposed group. Given the higher mortality at 6 and 24 months in the early weaning group, further study is required to find the right balance between risk of HIV transmission and risk of mortality from childhood illness.

Kumar A, St White H, Carter AO. Trends in the uptake of antenatal voluntary counselling and testing for HIV andHIV prevalence among childbearing women in Barbados, 1993-2004: evidence to gauge the effectiveness of HIV prevention measures. West Indian Med J. 2007 Jan;56(1):60-5.

Kumar and colleagues describe the long term trends in the uptake of antenatal voluntary counselling and testing (VCT) for Human Immunodeficiency Virus (HIV) and in the HIV prevalence among pregnant women. These data were used to gauge the impact of the National Acquired Immunodeficiency Syndrome (AIDS) Intervention Programme on preventing mother-to-child transmission (PMTCT) in Barbados. They conducted a population based study. Data for this report were drawn from the HIV Surveillance Programme for the mother-to-child transmission of HIV. The study population comprised all pregnant women who attended the various antenatal care clinics throughout Barbados during the period between 1993 and 2004. The uptake of the VCT for HIV among the pregnant women in Barbados has increased from 39.9% in 1993 to over 89.7% in 2004 (p < 0.0001). Mean annual HIV prevalence decreased from 10.5 per thousand women screened in 1993-1996 to 8.2 during 2001-2004 (p =0.121). Mean annual incidence rate of newly diagnosed HIV infection among the pregnant women declined from 8.8 per thousand women screened during 1993-1996 to 4.5 per thousand pregnant women screened during 2001-2004 (p = 0.004). Mean annual incidence rate of newly diagnosed HIV infection among the pregnant women aged less than 25 years during the corresponding period declined from 10.2 per thousand women aged less than 25 years screened to 4.8 per thousand women screened (p = 0.003). There has been a significant decline in the prevalence and incidence of HIV since the late-1990s. Although new infections are still occurring, the numbers are small. The decline may partly be explained by the impact of PMTCT and the general preventive measures on the spread of HIV among this population.

Editors’ note: The increase in HIV testing uptake in pregnancy from 40% to 90% over a 10-year period is striking. HIV prevalence remains high at 8% but newly diagnosed HIV infections have almost halved overall. The greater fall in incidence among women less than 25 years of age suggests that overall prevention efforts have found fertile ground among young people.

Rollins N, Little K, Mzolo S, Horwood C, Newell ML. Surveillance of mother-to-child transmission prevention programmes at immunization clinics: the case for universal screening. Rev Med Virol. 2007 Jun 1; [Epub ahead of print]

Surveillance programmes for prevention of mother-to-child transmission of HIV (PMTCT) fail to quantify numbers of infant HIV infections averted, often because of poor postnatal follow-up. Additionally, infected infants are often not identified early and only gain access to comprehensive HIV care and treatment late in their disease. Rollins et al conducted anonymous, unlinked, HIV prevalence testing on dried blood spot (DBS) samples from all infants attending 6 week immunization clinics at seven primary health care clinics offering PMTCT. Samples were tested for HIV antibodies (indicating maternal HIV infection) and those determined to be from HIV-exposed infants were tested for HIV RNA by polymerase chain reaction. Infant and child mortality rates were determined using birth histories. The authors collected samples from 2489 infants aged 4-8 weeks. HIV antibodies were identified in 931 infants [37.4%; 95% confidence interval (CI), 35.4-39.4], of whom 188 were HIV RNA positive. The estimated vertical transmission rate (VTR) was 20.2% (95% CI, 17.8-23.1%); 7.5% of all infants at this age were infected. Amongst mothers who reported that they had taken single-dose nevirapine for PMTCT, VTR was 15.0%. Amongst women who reported being HIV uninfected but whose infants had HIV antibodies, VTR was 30.5%. Infant mortality rates in KwaZulu Natal increased from 28/1000 live births in 1990-1994 to 92/1000 in 2000-2004. Anonymous HIV prevalence screening of all infants at immunization clinics is feasible to monitor the impact of PMTCT programmes on peri-partum infection; linked screening could identify infected children early for referral into care and treatment programmes.

Editors’ note: This surveillance programme using anonymous unlinked testing is not only a good programme measurement tool but revealed higher transmission rates among women who did not believe they were infected. Conducting in-depth interviews and focus groups with clinic attendees based on this information would help to develop effective communication messages to encourage pregnant women in this high prevalence setting to consider HIV testing more seriously. 

In the absence of interventions, 30-45% of exposed infants acquire human immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission. It remains unclear why some infants become infected while others do not, despite significant exposure to HIV-1 in utero, during delivery and while breastfeeding. Here we discuss the correlates of vertical transmission with an emphasis on factors that increase maternal HIV-1 levels, either systemically or locally in genital secretions and breast milk. Immune responses may influence maternal viral load, and data suggest that maternal neutralising antibodies reduce infection rates. In addition, infants may be capable of mounting HIV-specific cellular immune responses. We propose that both humoral and cellular responses are necessary to reduce infection because cell-free as well as cell-associated virus appears to play a role in vertical transmission. These distinct forms of the virus may be targeted most effectively by different components of the immune system. We also discuss the use of antiretrovirals to reduce transmission, focusing on the mechanisms of action of regimens currently used in developing country settings. We conclude that prevention relies not only on reducing maternal HIV-1 levels within blood, genital tract and breast milk, but also on pre- and/or post-exposure prophylaxis to the infant. However, HIV-1 has the capacity to mutate under drug pressure and rapidly acquires mutations conferring antiretroviral resistance. This review concludes with data on persistence of low-level resistance after delivery as well as recent guidelines for maternal and infant regimens designed to limit resistance. Copyright (c) 2007 John Wiley & Sons, Ltd.

Editors’ note: This review highlights the need for drugs that work to both reduce viral load in the mother and mop up any HIV that slips through to the baby.

Up to 40% of all mother-to-child transmission of HIV occurs by means of breast-feeding; yet, in developing countries, infant formula may not be a safe option. The World Health Organization recommends heat-treated breast milk as an infant-feeding alternative. Israel-Ballard and colleagues investigated the ability of a simple method, flash-heat, to inactivate HIV in breast milk from HIV-positive mothers. Ninety-eight breast milk samples, collected from 84 HIV-positive mothers in a periurban settlement in South Africa, were aliquoted to unheated control and flash-heating. Reverse transcriptase (RT) assays (lower detection limit of 400 HIV copies/mL) were performed to differentiate active versus inactivated cell-free HIV in unheated and flash-heated samples. The authors found detectable HIV in breast milk samples from 31% (26 of 84) of mothers. After adjusting for covariates, multivariate logistic regression showed a statistically significant negative association between detectable virus in breast milk and maternal CD4T-lymphocyte count (P = 0.045) and volume of breast milk expressed (P = 0.01) and a positive association with use of multivitamins (P = 0.03). All flash-heated samples showed undetectable levels of cell-free HIV-1 as detected by the RT assay (P< 0.00001). The authors conclude that flash-heat can inactivate HIV in naturally infected breast milk from HIV-positive women. Field studies are urgently needed to determine the feasibility of in-home flash-heating breast milk to improve infant health while reducing postnatal transmission of HIV in developing countries.

Editors’ note: Direct boiling of breast milk causes significant nutritional damage while standard pasteurization for 30 minutes requires temperature gauges and timing devices that are unavailable in many communities. Flash-heat is a recently developed, simple method that a mother can implement over an outdoor fire or in her kitchen. She expresses about 50 ml of breast milk into a locally available clean bottle and places it in a pot with warm water. As soon as the water comes to a rolling boil (100C) the bottle is removed and allowed to cool. This pilot study found the flash-heat method was capable of inactivating cell-free clade C HIV-1 while retaining most of the milk’s nutritional and antimicrobial properties. The next step: from the laboratory to field testing.

Simpore J, Pietra V, Pignatelli S, Karou D, Nadembega WM, Ilboudo D, Ceccherini-Silberstein F, Ghilat-Avoid-Belem WN, Bellocchi MC, Saleri N, Sanou MJ, Ouedraogo CM, Nikiema JB, Colizzi V, Perno CP, Castelli F, Musumeci S. Effective program against mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso. J Med Virol 2007;79:873-9.

The present research was aimed to prevent mother-to-child transmission of HIV; to use RT-PCR in order to detect, 6 months after birth, infected children; and to test the antiretroviral resistance of both children and mothers in order to offer them a suitable therapy. At the Saint Camille Medical Centre, 3,127 pregnant women (aged 15-44 years) accepted to be enrolled in the mother-to-child transmission prevention protocol that envisages: (i) Voluntary Counselling and Testing for all the pregnant women; (ii) Antiretroviral therapy for HIV positive pregnant women and for their newborns; (iii) either powdered milk feeding or short breast-feeding and RT-PCR test for their children; (iv) finally, pol gene sequencing and antiretroviral resistance identification among HIV positive mothers and children. Among the patients, 227/3,127 HIV seropositive women were found: 221/227 HIV-1, 4/227 HIV-2, and 2/227 mixed HIV infections. The RT-PCR test allowed the detection of 3/213 (1.4%) HIV infected children: 0/109 (0%) from mothers under ARV therapy and 3/104 (2.8%) from mothers treated with Nevirapine. All children had recombinant HIV-1 strain (CRF06_CPX) with: minor PR mutations (M36I, K20I) and RT mutations (R211K). Among them, two twins had Non-Nucleoside Reverse Transcriptase Inhibitor mutation (Y18CY). Both mothers acquired a major PR mutation (V8IV), investigated 6 months after a single-dose of Nevirapine. Prevention by single-dose of Nevirapine reduced significantly mother-to-child transmission of HIV, but caused many mutations and resistance to antiretroviral drugs. Based on present study the antiretroviral therapy protocol, together with the artificial-feeding, might represent the ideal strategy to avoid transmission of HIV from mother-to-child.

Editors’ note: Not having to wait into the second year of life to know whether your baby is infected or not is a great advantage for parents. Using two or more antiretroviral drugs for prophylaxis clearly reduces both HIV transmission and the risk of drug resistance in the mother and baby but success in rolling out single drug programmes remains elusive. It is also clear that breast milk replacement with milk powder can save lives only if sustainable access to milk powder can be ensured, the water supply is safe, and equipment is not contaminated. A better alternative if equipment is available is heat treating breast milk.

There have been no clinical trials in resource-rich regions that have addressed the question of which highly active antiretroviral therapy (HAART) regimens are more effective for optimal viral response in antiretroviral-naive, human immunodeficiency virus (HIV)-infected pregnant women. Data on 240 HIV-1-infected women starting HAART during pregnancy who were enrolled in the prospective European Collaborative Study from 1997 through 2004 were analyzed. An interval-censored survival model was used to assess whether factors, including type of HAART regimen, race, region of birth, and baseline immunological and virological status, were associated with the duration of time necessary to suppress viral load below undetectable levels before delivery of a newborn. Result revealed that protease inhibitor-based HAART was initiated in 156 women (65%), 125 (80%) of whom received nelfinavir, and a nevirapine-based regimen was initiated in the remaining 84 women (35%). Undetectable viral loads were achieved by 73% of the women by the time of delivery. Relative hazards of time to achieving viral suppression were 1.54 (95% confidence interval, 1.05-2.26) for nevirapine-based HAART versus PI-based regimens and 1.90 (95% confidence interval, 1.16-3.12) for western African versus non-African women. The median duration of time from HAART initiation to achievement of an undetectable viral load was estimated to be 1.4 times greater in women receiving PI-based HAART, compared with women receiving nevirapine-based HAART. Baseline HIV RNA load was also a significant predictor of the rapidity of achieving viral suppression by delivery, but baseline immune status was not. The authors of this study concluded that nevirapine-based HAART (compared with PI [mainly nelfinavir]-based HAART), western African origin, and lower baseline viral load were associated with shorter time to achieving viral suppression.

Editors’ note: Knowing which regimen is most effective in achieving an undetectable viral load by delivery seems like such a basic, essential question to answer. Almost three quarters of the women in this study had undetectable viral loads by the time of delivery, with nevirapine based treatment acting more quickly than the protease inhibitor-based regimens.

Suksomboon N, Poolsup N, Ket-Aim S. Systematic review of the efficacy of antiretroviral therapies for reducing the risk of mother-to-child transmission of HIV infection. J Clin Pharm Ther 2007 Jun;32:293-311.

Suksomboon and colleagues’ objective was to evaluate the efficacy of antiretroviral therapies in reducing the risk of mother-to-child transmission of HIV infection. The authors used a systematic review and meta-analysis of randomized controlled trials. Clinical trials of anti-retrovirals were identified through electronic searches (MEDLINE, EMBASE, BIOSIS, EBM review and the Cochrane Library) up until November 2006. Historical searches of reference lists of relevant randomized controlled trials, and systematic and narrative reviews were also undertaken. Studies were included if they were (i) randomized controlled trials of any antiretroviral therapy aimed at decreasing the risk of mother-to-child transmission of HIV infection, (ii) reporting outcomes in terms of HIV infection in infant, infant death, stillbirth, premature delivery, or low birth weight. The data were extracted by a single investigator and checked by a second investigator. Disagreements were resolved through discussion or a third investigator. The efficacy was estimated using relative risk (RR), risk difference (RD) and number needed to treat (NNT) together with 95% confidence intervals. Results: Fifteen trials were included in the systematic review. Based on five placebo-controlled trials, a zidovudine regimen reduced the risk of mother-to-child transmission by 43% (95% CI:29-55%). The incidence of low birth weight seems to be decreased with zidovudine (pooled RR 0.75, 95% CI: 0.57-0.99). The efficacy of short-short course of zidovudine was comparable with that of the long-short course. Nevirapine monotherapy given to mothers and babies as a single dose reduced the risk of vertical transmission compared with an intra-partum and post-partum regimen of zidovudine (RR 0.60, 95% CI: 0.41-0.87). Zidovudine plus lamivudine was effective in reducing the risk of maternal-child transmission of HIV (RR 0.63, 95% CI: 0.45-0.90). Adding zidovudine to single-dose nevirapine in babies was no more effective than nevirapine alone (pooled RR 0.88, 95% CI: 0.47-1.63), nor was there any significant difference between zidovudine plus lamivudine and nevirapine. In mothers who were treated with standard antiretroviral therapy, no additional benefit was observed with the addition of a single dose of nevirapine in mothers and newborns. In addition, for mothers who received zidovudine prophylaxis, a two-dose intra-partum/newborn nevirapine reduced the risk of HIV infection and death of babies by 68% (95% CI: 39-83%) and 80% (95% CI: 10-95%), respectively, when compared with placebo. In conclusion, the available evidence suggests that zidovudine alone or in combination with lamivudine and nevirapine monotherapy is effective for the prevention of mother-to-child transmission of HIV. They may also be beneficial in reducing the risk of infant death. Different antiretroviral regimens appear to be comparably effective in reducing HIV transmission from mothers to babies. In mothers already receiving zidovudine prophylaxis, adding a single dose of nevirapine to mothers during labour and giving the same drug to infants may further decrease the risk of vertical transmission and infant death.

Editors’ note: This review found single dose nevirapine to be more effective than intra-and post-partum zidovudine but adding two-dose intra partum/newborn nevirapine to existing zidovudine prophylaxis reduced the risk of infant infection by 68%. At this point the issue is less which regimen than any regimen — coverage levels for prevention of mother-to-child transmission remain unconscionably low in many low-and middle-income countries.

Coovadia HM, Rollins NC, Bland RM, Little K, Coutsoudis A, Bennish ML, Newell ML. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 2007;369:1107-16.

Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. Coovadia and colleagues assessed the HIV-1 transmission risks and survival associated with exclusive breastfeeding and other types of infant feeding. 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semi urban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Cox’s proportional hazard was used to quantify associations with maternal and infant factors. 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile [Q1] to third quartile [Q3], 122-174 days). 14.1% (95% CI 12.0-16.4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19.5% (17.0-22.4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per muL (adjusted hazard ratio [HR] 3.79; 2.35-6.12) and birth weight less than 2500 g (1.81, 1.07-3.06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4.04% (2.29-5.76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10.87, 1.51-78.00, p=0.018), as were infants who at 12 weeks received both breast milk and formula milk (1.82, 0.98-3.36, p=0.057). Cumulative 3-month mortality in exclusively breastfed infants was 6.1% (4.74-7.92) versus 15.1% (7.63-28.73) in infants given replacement feeds (HR 2.06, 1.00-4.27, p=0.051). The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.

Editors’ note: In October 2006, examination of new evidence on HIV transmission through breastfeeding from 3 large cohort studies in Côte d’Ivoire, South Afica and Zimbabwe; on morbidity and mortality; on improving infant feeding practices; and on programme performance led to a consensus statement (click here). HIV-infected women are recommended to breastfeed exclusively for the first 6 months of life unless replacement feeding is acceptable, feasible, affordable, sustainable and safe for them and their infants (known as AFASS).