Highly Active Antiretroviral Therapy Versus Zidovudine for Prevention of Mother-to-Child Transmission in a Programmatic Setting, Botswana

Dryden‐Peterson, Scott; Jayeoba, O.; Hughes, Michael D.; Jibril, Haruna; Keapoletswe, Koona; Tlale, Josephine; Modise, Taolo A.; Asmelash, Aida; Moyo, Sikhulile; Widenfelt, Erik van; Makhema, Joseph; Essex, Max; Shapiro, Roger; Lockman, Shahin

doi:10.1097/qai.0b013e31822d4063

Cited by 17 publications

(14 citation statements)

References 15 publications

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“…However, more information on the safety and effectiveness of the preventive regimens can help in defining optimized strategies. In our study maternal ART administration was significantly beneficial for women’s health (with a very low mortality rate) and highly effective, with a transmission rate similar to other observational and randomized studies [2,13,14]. Although the very limited number of infections did not allow us to establish a significant correlation between one or more factors and the overall risk of transmission, some of our findings were intriguing.…”

Section: Discussionsupporting

confidence: 64%

Maternal Antiretroviral Therapy for the Prevention of Mother-To-Child Transmission of HIV in Malawi: Maternal and Infant Outcomes Two Years after Delivery

et al. 2013

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BackgroundOptimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.Methodology/Principal FindingsA total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm3 at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm3. HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm3 were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm3 was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.ConclusionsHIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

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Section: Discussionsupporting

confidence: 64%

Maternal Antiretroviral Therapy for the Prevention of Mother-To-Child Transmission of HIV in Malawi: Maternal and Infant Outcomes Two Years after Delivery

et al. 2013

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“…However, with maternal highly active antiretroviral therapy (HAART), less than 2% of infants acquire HIV infection. [3]–[5] With improved access to maternal HAART during pregnancy and breastfeeding, [6] the recommendation to provide empiric cotrimoxazole prophylaxis for all HIV-exposed infants has been questioned. [7].…”

Section: Introductionmentioning

confidence: 99%

Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants

et al. 2013

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BackgroundProphylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia.MethodsWe compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana.ResultsA total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, −0.69% (95% confidence interval [CI] −2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI −1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93).ConclusionsSevere anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants.ClinicalTrials.gov Registration NumbersNCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).

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“…Treatment as prevention also has been examined in maternal to child transmission with early studies showing reduction of maternal to child transmission from 20% to <2% [89]. A recent study from Botswana showed 2.5% of infants born to mothers receiving zidovudine were HIVinfected compared to 0.4% of infants born to mothers on combination antiretroviral therapy (cART, previously known as highly active antiretroviral therapy or HAART) [90]. This data further solidifies the need for earlier diagnosis of HIV infected individuals and broader treatment of HIV-infected individuals to prevent new HIV infections.…”

Section: Treatment As Preventionmentioning

confidence: 97%

HIV in Africa: Challenges and Directions for the Next Decade

Gilliam

Patel

Talwani

et al. 2011

Curr Infect Dis Rep

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Africa carries a disproportionate burden of the global HIV endemic, accounting for two thirds of the global 33.3 million people living with HIV. While tremendous advances have been made in addressing the HIV epidemic in Africa, considerable challenges remain. Testing for HIV increased by 86% from 2007 to 2009 but more than 75% of people 15-49 years remain unaware of their HIV status. CD4 count at diagnosis tends to be low and linkage to care and treatment is suboptimal. The scale-up of antiretroviral therapy is ongoing but is hampered by the lack of diagnostic capability to monitor response to therapy and a substantial healthcare workforce shortage. Prevention strategies such as male circumcision, pre-exposure prophylaxis, and antiretroviral therapy for prevention have generated great excitement but cost and healthcare infrastructure deficiencies may limit their widespread applicability. Operational research to validate and inform treatment decisions, health care policies, and prevention strategies is sorely needed.

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Highly Active Antiretroviral Therapy Versus Zidovudine for Prevention of Mother-to-Child Transmission in a Programmatic Setting, Botswana

Cited by 17 publications

References 15 publications

Maternal Antiretroviral Therapy for the Prevention of Mother-To-Child Transmission of HIV in Malawi: Maternal and Infant Outcomes Two Years after Delivery

Maternal Antiretroviral Therapy for the Prevention of Mother-To-Child Transmission of HIV in Malawi: Maternal and Infant Outcomes Two Years after Delivery

Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants

HIV in Africa: Challenges and Directions for the Next Decade

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