Lessons learned from early implementation of option B+: the Elizabeth Glaser Pediatric AIDS Foundation experience in 11 African countries.

BACKGROUND: "Option B+" is a World Health Organization-recommended approach to prevent mother-to-child HIV transmission whereby all HIV-positive pregnant and lactating women initiate lifelong antiretroviral therapy (ART). This review of early Option B+ implementation experience is intended to inform Ministries of Health and others involved in implementing Option B+. METHODS: This implementation science study analyzed data from 11 African countries supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) to describe early experience implementing Option B+. Data are from 4 sources: (1) national guidelines for prevention of mother-to-child HIV transmission and Option B+ implementation plans, (2) aggregated service delivery data between January 2013 and March 2014 from EGPAF-supported sites, (3) field visits to Option B+ implementation sites, and (4) relevant EGPAF research, quality improvement, and evaluation studies. RESULTS: Rapid adoption of Option B+ led to large increases in percentage of HIV-positive pregnant women accessing ART in antenatal care. By the end of 2013, most programs reached at least 50% of HIV-positive women in antenatal care with ART, even in countries using a phased approach to implementation. Scaling up Option B+ through integrating ART in maternal and child health settings has required expansion of the workforce, and task shifting to allow nurse-led ART initiation has created staffing pressure on lower-level cadres for counseling and community follow-up. Complex data collection needs may be impairing data quality. DISCUSSION: Early experiences with Option B+ implementation demonstrate promise. Continued program evaluation is needed, as is specific attention to counseling and support around initiation of lifetime ART in the context of pregnancy and lactation.

A multi-disciplinary approach to implementation science: the NIH-PEPFAR PMTCT implementation science alliance.

In resource-limited countries, interventions to prevent mother-to-child HIV transmission (PMTCT) have not yet realized their full potential health impact, illustrating the common gap between the scientific proof of an intervention's efficacy and effectiveness and its successful implementation at scale into routine health services. For PMTCT, this gap results, in part, from inadequate adaptation of PMTCT interventions to the realities of the implementation environment, including client and health care worker behaviors and preferences, health care policies and systems, and infrastructure and resource constraints. Elimination of mother-to-child HIV transmission can only be achieved through understanding of key implementation barriers and successful adaptation of scientifically proven interventions to the local environment. Central to such efforts is implementation science (IS), which aims to investigate and address major bottlenecks that impede effective implementation and to test new approaches to identifying, understanding, and overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions. Advancing IS will require deliberate and strategic efforts to facilitate collaboration, communication, and relationship-building among researchers, implementers, and policy-makers. To speed the translation of effective PMTCT interventions into practice and advance IS more broadly, the US National Institutes of Health, in collaboration with the President's Emergency Plan for AIDS Relief launched the National Institutes of Health/President's Emergency Plan for AIDS Relief PMTCT IS Alliance, comprised of IS researchers, PMTCT program implementers, and policy-makers as an innovative platform for interaction and coordination.

Lessons from the President's Emergency Plan for AIDS Relief: from quick ramp-up to the role of strategic partnership.

In its first five years, the President's Emergency Plan for AIDS Relief (PEPFAR)--the largest commitment ever by any nation to combat a single disease--succeeded in getting 2.1 million people on antiretroviral treatment and 10.1 million people in care; prevented an estimated 237,600 HIV infections in infants; and saved an estimated 3.28 million adult years of life. Much of the global program's success can be attributed to early decisions to implement new structures and approaches designed to meet its ambitious targets quickly, overcome bureaucratic inertia, and ensure continued progress. A unified US government program was created with a single coordinator. There was a focus on quick ramp-up, strategic partnerships, and sustainable local ownership. Accountability and performance were emphasized. These new approaches played critical roles in translating the unprecedented resources and political support for PEPFAR into improved health for millions of people. Successful aspects of the way in which PEPFAR was organized and implemented, along with less successful or deficient ones, offer lessons for any large, complex international health initiative.

PEPFAR scale-up of pediatric HIV services: innovations, achievements, and challenges.

HIV/AIDS has had a profound impact on children around the world since the start of the epidemic. There are currently 3.4 million children under the age of 15 years living with HIV globally, and more than 450,000 children currently receiving lifesaving antiretroviral treatment. This article describes efforts supported by the President's Emergency Plan for AIDS Relief (PEPFAR) to expand access to treatment for children living with HIV in high-burden countries. The article also highlights a series of case studies that illustrate the impact that the PEPFAR initiative has had on the pediatric HIV epidemic. Through its support of host governments and partner organizations, the PEPFAR initiative has expanded HIV testing and treatment for pregnant women to reduce vertical transmission of HIV, increased access to early infant diagnosis for HIV-exposed infants, improved training and resources for clinicians who provide pediatric care and antiretroviral treatment, and, through public-private partnerships with pharmaceutical manufacturers, helped increase the number of medications available for the treatment of HIV-infected children in resource-limited settings.

Factors associated with non-disclosure of HIV infection status of new mothers in Bangkok.

The objective of this study was to estimate HIV disclosure rates and identify factors that predict non-disclosure in Thai women who tested HIV positive during pregnancy or at delivery. This was a cohort study evaluating the implementation of prevention of mother-to-child HIV transmission programs at two Bangkok hospitals in 1999-2003. All HIV-infected women who delivered during the study period were enrollment eligible. Thai-language questionnaires were used to collect baseline data before discharge from the hospital. At the 1 and 4 month follow-up visits, women were asked if they had disclosed their HIV status. Of the 799 women who enrolled, 647 (81.0%) completed follow-up at 1 and 4 months. Four hundred fifty-three (70.0%) women disclosed their status by 1 month. Of the 194 women who had not disclosed by 1 month, 48 (24.7%) had disclosed their status by 4 months. An independent increased odds of non-disclosure by 1 month was associated with not having a partner tested for HIV (OR=5.83, 95% CI=3.19-9.08) or not knowing if the partner was ever tested for HIV (OR=1 3.02, 95% Cl=5.26-32.28), first learning of HIV positive status during delivery (OR=6.84, 95% CI=2.36-19.81) or after delivery (OR=3.14, 95% CI=1.57-6.26) and having >2 lifetime sexual partners (OR=1.71, 95% CI=1.04-2.82). Not living with a partner every day was associated with non-disclosure by 4 months in those women who had not disclosed by 1 month (OR=2.28, 95% CI=1.43-3.64). Despite high rates of disclosure by 1 month, 22.6% of women still had not disclosed their HIV status to their partners by 4 months. The benefits of disclosure warrant effective interventions targeted at women at risk for non-disclosure.

Evaluating programs to prevent mother-to-child HIV transmission in two large Bangkok hospitals, 1999-2001.

The 2 largest maternity hospitals in Bangkok implemented comprehensive programs to prevent mother-to-child HIV transmission in 1998. We conducted a cross-sectional survey of post-partum HIV-infected women in 1999 through 2001 to evaluate these programs. Women were given structured interviews at 0 to 3 days, 1 month, and 2 months postpartum. Medical records of women and their newborns were reviewed. Of 488 enrolled women, 443 (91%) had antenatal care: 391 (88%) at study hospitals and 52 (12%) elsewhere. The HIV diagnosis was first known before pregnancy for 61 (13%) women, during pregnancy for 357 (73%) women, during labor for 22 (5%) women, and shortly after delivery for 48 (10%) women. Antenatal zidovudine (ZDV) was used by 347 (71%) women, and intrapartum ZDV was used by 372 (76%) women. Twelve (55%) of the 22 women who first learned of their HIV infection during labor took intrapartum ZDV. All 495 newborn infants started prophylactic ZDV; the first dose was given within 12 hours for 491 (99%) children. Ten (2%) children were breast-fed at least once by their mother, and 10 (2%) were breast-fed at least once by someone else. Although uptake of services was high, inconsistent antenatal care, fear of stigmatization, and difficulty in disclosing HIV status prevented some women from using services.

Survival, disease manifestations, and early predictors of disease progression among children with perinatal human immunodeficiency virus infection in Thailand.

OBJECTIVE: To describe survival and signs of human immunodeficiency virus (HIV) infection in perinatally infected children in Thailand. METHODS: At 2 large Bangkok hospitals, 295 infants born to HIV-infected mothers were enrolled at birth from November 1992 through September 1994 and followed up with clinical and laboratory evaluations every 1 to 3 months for 18 months. Infected children remained in follow-up thereafter. For the infected children, we used data collected through October 2000 to estimate survival times and compare characteristics among those whose disease progressed at rapid (died within 1 year), intermediate (died at 1-5 years), and slow (survived at least 5 years) rates. RESULTS: None of the 213 uninfected children died during the follow-up period. Of the 68 infected children, 31 (46%) died; median survival was 60 months (95% confidence interval: 31-89 months). The most common cause of death was pneumonia (52% of deaths). Thirty-two children (47%) started antiretroviral therapy. Six children died in their first year before developing specific signs of HIV infection; all others developed signs of HIV infection between 1 and 42 months old (median: 4 months). Severe clinical (Centers for Disease Control and Prevention Class C) conditions were diagnosed in 23 children at a median age of 12 months, 15 (65%) of whom died a median of 3 months later. Compared with children whose disease progressed slowly, those whose disease progressed rapidly gained less weight by 4 months old (median 1.7 vs 2.6 kg), and their mothers had higher viral loads (median 5.1 vs 4.5 log(10) copies/mL) and lower CD4(+) counts (median 350 vs 470 cells/ micro L) at delivery. CONCLUSIONS: Among HIV-infected Thai children, survival times are longer than among children in many African countries, but shorter than among children in the United States and Europe. Signs of HIV develop early in most children. Growth failure and advanced maternal disease can predict rapid HIV disease progression and may be useful markers for treatment decisions.

Preventing mother-to-child HIV transmission: the first year of Thailand's national program.

CONTEXT: Each year in Thailand, about 10,000 children are born at risk for mother-to-child human immunodeficiency virus (HIV) transmission. In 2000, Thailand implemented a national program to prevent mother-to-child HIV transmission. OBJECTIVE: To describe the results of implementation of the program. DESIGN: Monthly collection of summary data from hospitals. SETTING: Public health hospitals (n = 822) in all 12 regions of Thailand, representing 75 provinces, excluding Bangkok. PARTICIPANTS: Women giving birth from October 2000 through September 2001, including HIV-seropositive women and their neonates. MAIN OUTCOME MEASURES: Percentages of women giving birth who were tested for HIV, HIV-seropositive women giving birth who received antenatal prophylactic antiretroviral drugs, and HIV-exposed neonates who received prophylactic antiretroviral drugs and infant formula. RESULTS: Among 573,655 women (range, 27,344-77,806 by region) giving birth, 554,912 (96.7%) received antenatal care (range, 91.9%-98.8% by region). Of 554,912 women giving birth who had antenatal care, 517,488 (93.3%) were tested for HIV (range, 87.7%-99.4% by region) before giving birth; of 18,743 women giving birth who did not have antenatal care, 13,314 (71.0%) were tested for HIV (range, 21.7%-92.9% by region). Of 6646 HIV-seropositive women giving birth, 4659 (70.1%) received prophylactic antiretroviral drugs before delivery (range, 55.3%-81.2% by region). Of 6475 neonates of HIV-seropositive women, 5741 (88.7%) received prophylactic antiretroviral drugs (range, 67.4%-96.9% by region) and 5386 (83.2%) received infant formula (range, 65.3%-100% by region). CONCLUSIONS: Major program components of Thailand's national program for preventing mother-to-child HIV transmission were implemented. Thailand's experience may encourage other developing countries to implement or expand similar national programs.

National program for preventing mother-child HIV transmission in Thailand: successful implementation and lessons learned.

OBJECTIVE: To describe the development, components, and initial uptake of Thailand's national program for preventing mother-child HIV transmission. DESIGN: Historical review, interpretation of experience, national program monitoring. SETTING: Public health system, Thailand. PARTICIPANTS: Policymakers, clinicians, HIV-infected pregnant women. INTERVENTION: Voluntary counseling and HIV testing of pregnant women; short-course zidovudine for HIV-infected women and their infants and formula feeding for infants. MAIN OUTCOME MEASURES: Program components implemented and program uptake. RESULTS: Research, monitoring and evaluation of pilot projects, training, and policy-making provided the information, experience, infrastructure, and guidance to develop a program for preventing mother-child HIV transmission that was implemented in all Ministry of Public Health hospitals in Thailand in 2000. A national system was established to monitor program implementation. Monitoring reports were received from 669 hospitals in 65 provinces for the period October 2000 through July 2001. During this period, 93% of 318 721 women who gave birth were tested for HIV; 69% of 3958 HIV-infected women giving birth received zidovudine; and 86% and 80% of the 3865 children born to HIV-infected women received zidovudine and infant formula, respectively, through the program. CONCLUSIONS: A national program for preventing mother-child HIV transmission was successfully implemented in Thailand. Early monitoring indicates good program uptake. Lessons learned from implementing this program include the importance of paying attention to counseling, communication, and training in the program, and using pilot projects and focused monitoring and evaluation data to guide the program development, expansion, and improvement.

Maternal characteristics associated with antenatal, intrapartum, and neonatal zidovudine use in four US cities, 1994-1998.

OBJECTIVES: To evaluate implementation of 1994 United States Public Health Service guidelines for zidovudine (ZDV) use in HIV-infected women and their newborns by describing the prevalence of use of perinatal ZDV and other antiretrovirals and by investigating determinants of not receiving perinatal ZDV. DESIGN/METHODS: The Perinatal AIDS Collaborative Transmission Study is a prospective cohort study designed to collect information related to mother-to-child HIV transmission that was conducted in New York City (NY), Newark (NJ), Baltimore (MD), and Atlanta (GA), U.S.A. The current analysis was restricted to infants born between July 1994 and June 1998. RESULTS: Utilization rates for antenatal, intrapartum, and neonatal ZDV increased from 41% to 70% during the 4-year period. Use of combination antiretrovirals increased from fewer than 2% of women in 1994 to 1995 to 35% in 1997 to 1998. Antenatal and neonatal ZDV use increased each year, but intrapartum ZDV use reached a plateau after 1996. Mother-infant pairs with the following characteristics were less likely to have received a complete 3-part ZDV regimen: older maternal age, CD4 count >500 cells/microl, preterm birth, cocaine or heroin use during pregnancy, positive newborn drug screen test result, and smoking or alcohol use during pregnancy. By multivariate logistic regression adjusted for hospital and year of birth, cocaine or heroin use during pregnancy (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6-3.3), maternal CD4 count (OR, 0.4; 95% CI, 0.2-0.8; comparing <200 with >500 cells/microl), and preterm birth (OR, 1.6; 95% CI, 1.1-2.5) remained independently associated with not receiving the complete ZDV regimen. CONCLUSIONS: ZDV use by pregnant HIV-infected women and their infants has increased dramatically since publication of the 1994 guidelines. Nevertheless, women who abuse substances, give birth preterm, or have less advanced immunosuppression, were at substantial risk of not receiving the complete ZDV regimen.

Barriers to universal prenatal HIV testing in 4 US locations in 1997.

OBJECTIVES: We determined rates of prenatal HIV testing and investigated barriers to testing. METHODS: We surveyed 1362 representative parturient women from 7 hospitals in 4 locations of the United States. RESULTS: Overall, 89.9% of women reported being offered HIV testing and 69.6% reported being tested. Proportions of women not offered testing differed by location (range = 5.2%-16.3%), as did proportions not tested (range = 12.2%-54.4%). Among women who perceived that their clinicians had not recommended testing, 41.7% were tested, compared with 92.8% of women who perceived a strong recommendation (P < .05). Private insurance for prenatal care was also associated with not being tested. Women gave multiple reasons for not being tested, most commonly not being at risk, having been tested recently, and the test's not being offered or recommended, cited by 55.3%, 39.1% and 11.1% of women, respectively. CONCLUSIONS: Although most parturient women were offered a prenatal HIV test and got tested, testing proportions did not reach national goals and differed significantly by location and payment status. Concern about testing consequences was not a major barrier. Perception of clinicians' recommendations strongly influenced testing. Changing provider practices will be essential to implementing universal prenatal HIV testing.

HIV seroconversion during pregnancy and risk for mother-to-infant transmission.

Pregnant women infected with HIV-1 were enrolled in a prospective mother-to-infant transmission study from 1992 through 1994 in Bangkok. In participating hospitals, voluntary HIV testing was routinely offered at the beginning of antenatal care and again in the middle of the third trimester of pregnancy. Women who seroconverted to HIV during pregnancy were compared with women who had tested positive on their first antenatal test. Maternal HIV RNA levels were determined during pregnancy, at delivery, and postpartum using RNA polymerase chain reaction (PCR), and infection status in infants was determined by DNA PCR. No infants were breast-fed, but prophylactic antiretroviral therapy was not yet used in Thailand to prevent transmission from mother to infant. Among enrolled women, 16 who seroconverted during pregnancy and 279 who were HIV-1-seropositive at their first antenatal test gave birth. Median plasma RNA levels at delivery were similar for the two groups (17,505 and 20,845 copies/ml, respectively; p =.8). Two (13.3%) of 15 infants born to women who seroconverted and 66 (24.8%) of 266 infants born to previously HIV-seropositive women were infected with HIV (p =.5). There was no increased risk for mother-to-infant HIV transmission and no significant difference in viral load at delivery between HIV-infected women who seroconverted to HIV during pregnancy and those who were HIV-seropositive when first tested.

Safety of late in utero exposure to zidovudine in infants born to human immunodeficiency virus-infected mothers: Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group.

BACKGROUND: Short-course zidovudine (ZDV) given in the late antenatal period can reduce mother-infant human immunodeficiency virus (HIV) transmission by one half. Because this intervention is being implemented in developing countries, evidence of its safety is needed. METHODS: In a randomized, double-blinded, placebo-controlled trial in Bangkok, HIV-infected pregnant women received either ZDV (300 mg twice daily from 36 weeks' gestation until labor, then every 3 hours until delivery) or an identical placebo regimen. Infants were evaluated at birth and at 1, 2, 4, 6, 9, 12, 15, and 18 months of age. Growth, clinical events, and hematologic and immunologic measurements were compared between treatment groups. RESULTS: Of the 395 children born (196 in ZDV group and 199 in placebo group), 330 were uninfected, 55 were infected, and 10 had indeterminate infection status. Overall, 319 children (81%) completed 18 months of follow-up, and 14 (4%) died before 18 months of age. Among uninfected children, the mean hematocrit was lower in the ZDV group at birth (49.1% vs 51.5%) but not at later ages; mean weight, height, head circumference, and CD4(+) and CD8(+) T lymphocyte counts were similar in both groups at all ages. Five uninfected children in the ZDV group but only one in the placebo group had a febrile convulsion. No other signs suggestive of mitochondrial dysfunction and no tumors were observed. Among infected children, an estimated 62% in the ZDV group and 77% in the placebo group survived free of Centers for Disease Control and Prevention class C disease during the 18-month follow-up. CONCLUSIONS: No significant adverse events were associated with short-course ZDV during 18 months of follow-up in this population.

Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes.

OBJECTIVES: To evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV-1 infection and to investigate early viral dynamics in infected infants. DESIGN: A cohort study of 395 non-breastfed infants born to HIV-infected mothers in a randomized clinical trial of short-course antenatal zidovudine. METHODS: Infant venous blood specimens collected at birth, 2 months, and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR, results were compared with later DNA PCR results and to antibody results at 18 months. The HIV-1 subtype of the mother's infection was determined by peptide serotyping. RESULTS: In the study, 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth, and 100% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA-positive tested RNA-positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants, the median viral load of RNA-positive specimens was 407,000 copies/ml (5.6 log10) at birth, 3, 700,000 copies/ml (6.6 log10) at 2 months, and 1,700,000 copies/ml (6.2 log10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure, or RNA level at birth. CONCLUSION: This RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection, detecting nearly half of infected infants at birth, and 100% at 2 and 6 months, with 100% specificity. Infected infant viral RNA levels were very high at 2 and 6 months, and were unaffected by maternal zidovudine treatment.

Evaluating a new strategy for prophylaxis to prevent Pneumocystis carinii pneumonia in HIV-exposed infants in Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVE: To evaluate a strategy for prophylaxis against Pneumocystis carinii pneumonia (PCP) for infants in Thailand. METHODS: HIV-infected women were offered trimethoprim-sulfamethoxazole for PCP prophylaxis for their children at 1-2 months of age. When the children reached 6 months of age, investigators simulated a decision to continue or stop prophylaxis on the basis of clinical criteria, and compared their decisions with results of polymerase chain reaction (PCR) testing for HIV. We calculated the proportions of children who received and completed prophylaxis, and compared the rates of pneumonia and death from pneumonia with rates from an earlier prospective cohort. RESULTS: Of 395 eligible infants, 383 (97%) started prophylaxis. By 6 months of age, 10 (2.6%) were lost to follow-up, three (0.8%) were non-adherent, seven (2%) had stopped because of adverse events, four (1%) had died, and 359 (94%) still received prophylaxis. At 6 months of age, 30 (70%) of 43 HIV-infected children and 16 (5%) of 316 uninfected children met the clinical criteria to continue prophylaxis. The incidence of pneumonia at 1 to 6 months of age was 22% (15/68) in the earlier cohort, and 13% (6/46) in the recent cohort [relative risk (RR) 0.6, 95% confidence interval (CI) 0.3-1.4; P= 0.22]; mortality rates were 9% and 4%, respectively (RR 0.5; 95% CI 0.1-2.3; P = 0.47). CONCLUSION: This PCP prophylaxis strategy appeared to be acceptable and safe, may have reduced morbidity and mortality from pneumonia, and should be considered in developing countries where early laboratory diagnosis of perinatal HIV infection is unavailable.

Implementing short-course zidovudine to reduce mother-infant HIV transmission in a large pilot program in Thailand.

OBJECTIVES: To describe a pilot mother-infant HIV prevention program started by the Ministry of Public Health of Thailand in July 1998 and to report on the first year of its implementation. DESIGN: Analysis of monthly summaries of data from project logbooks, simple data forms in antenatal clinics and delivery rooms, site visits and workshops, mail survey. SETTING: All 89 public hospitals in seven north-eastern provinces of Thailand. PARTICIPANTS: Childbearing women, program officials. INTERVENTIONS: Counseling and HIV testing for pregnant women, short-course antenatal zidovudine for HIV-infected pregnant women, and infant formula for their children. MAIN OUTCOME MEASURES: Proportion of women with HIV test, proportion of HIV-infected women receiving zidovudine. RESULTS: Of 75,308 women who gave birth between July 1998 and June 1999, 74,511 (98.9%) had antenatal care, 51,492 (69.1%) in the same district and 23,019 (30.9%) outside the district where they gave birth. HIV test results were available at delivery for 46,648 (61.9%) women, 410 (0.9%) of whom tested positive. Of these HIV-infected women, 259 (63.2%) participated in the zidovudine program and 6 (1.5%) received zidovudine from other sources. The proportion of women whose HIV test results were known and proportion of HIV-infected women who received zidovudine increased significantly during the year. CONCLUSIONS: A mother-infant HIV prevention program using short-course antenatal zidovudine was quickly implemented in a large region of Thailand with moderate HIV prevalence. This successful experience is leading to national implementation of a perinatal HIV prevention program in Thailand and may prompt other developing countries to start similar programs.

Antiretroviral therapy and declining AIDS mortality in New York City.

The objective was to evaluate the association between antiretroviral therapy and AIDS mortality in New York City (NYC). Design was a population-based case-control study. We randomly selected 150 case patients and 150 control patients whose AIDS diagnosis was made during 1994 to 1996 (male:female, 2:1) from among 19,238 persons reported to the NYC Health Department HIV/AIDS Reporting System (HARS). Case patients had died of AIDS-related causes in 1996. Control patients, category matched with case patients on gender, were not known to have died by the end of 1996. Analysis was performed on 279 patients (142 cases and 137 controls). Cases and controls were similar in age, gender, race, HIV transmission category, and health insurance coverage. The median baseline CD4 count was 30 cells/microL for those who died and 103 cells/microL for survivors (p < 0.001). The prescription of HAART (antiretroviral combination that includes at least one protease inhibitor) in 1996 was strongly associated with survival in univariate analysis (OR = 5.1, 95%CI = 2.5-10.2). This association remained in a logistic regression analysis after adjusting for sex, age, race, health insurance status, HIV transmission categories, year of AIDS diagnosis, baseline CD4 count, and other antiretroviral therapy (AOR = 8.6, 95%CI = 3.5-20.7). Prescription of combination therapy other than HAART in 1996 and baseline CD4 count were also associated with survival, but less strongly so. The survival benefit of HAART extends beyond the confines of a few highly selected patients into the "real world," reducing AIDS deaths at the population level. This population-based study supports the likelihood that the introduction of HAART in 1996 played a primary role in the decline in NYC AIDS mortality.

Interventions to prevent vertical transmission of HIV-1: effect on viral detection rate in early infant samples.

OBJECTIVE: To determine whether mode of delivery or the use of maternal or neonatal antiretroviral prophylaxis influence the age when HIV-1 can first be detected in infected infants, particularly the probability of detection at birth. METHODS: In a collaboration between four multicentre studies, data on 422 HIV-1 infected infants who were assessed by HIV-1 DNA PCR or cell culture before 14 days of age were analysed. Weibull mixture models were used to estimate the cumulative proportion of infants with detectable levels of HIV-1 according to use of maternal/neonatal antiretroviral therapy (mainly zidovudine monotherapy) and mode of delivery. RESULTS: HIV-1 was detected in 162 infants (38%) when they were first tested, at a median age of 2 days. At birth, it was estimated that 36% [95% confidence interval (CI), 31-41%] of infants have levels of virus that can be detected by DNA PCR or cell culture. This percentage was not associated with either mode of delivery (35% for vaginal delivery versus 40% for cesarean section delivery; P = 0.4) or the use of maternal or neonatal antiretroviral prophylaxis. Among infants with undetectable levels of HIV-1 at birth, the median time to viral detectability was estimated to be 14.8 days (95% CI, 12.9-16.8 days). This time was increased by 15% (95% CI, -11 to 48%; P = 0.3) among infants who were exposed to antiretroviral therapy postnatally compared with infants who were not exposed. No effect was observed for mode of delivery. CONCLUSIONS: The outcome of an early virological test for HIV-1 is thought to be related directly to the timing of transmission and cesarean section delivery primarily reduces the risk of intrapartum transmission. The absence of an association between mode of delivery and viral detectability at birth was therefore unexpected. There was no evidence that foetal or neonatal exposure to prophylactic zidovudine delays substantially the diagnosis of infection, although this cannot be inferred for combination antiretroviral therapy.

Oral zidovudine during labor to prevent perinatal HIV transmission, Bangkok: tolerance and zidovudine concentration in cord blood. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To evaluate tolerance for the oral administration of zidovudine (ZDV) during labor and measure the resulting ZDV concentrations in umbilical cord blood. DESIGN: A cross-sectional study of women in a placebo-controlled trial of short-course ZDV (twice a day from 36 weeks' gestation until labor and every 3 h during labor) to prevent perinatal HIV transmission in Bangkok. METHODS: Umbilical cord blood was collected. Sixty control specimens and specimens from 372 women (182 in the ZDV group, 190 in the placebo group) were tested for ZDV by radioimmunoassay (lower detection limit < 1 ng/ml). RESULTS: All women in the ZDV group took one or more labor dose, 170 (93%) took their last dose within 3 h of delivery, and only five (3%) experienced nausea or vomiting, a proportion similar to the placebo group. The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml (range, < 1-1133 ng/ml); 31 (17%) specimens were less than 130 ng/ml (0.5 microM), the concentration thought to be active against HIV in vitro. Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses, 290 ng/ml in those taking three or four doses, and 293 ng/ml in those taking more than four doses (P < 0.01). The ZDV concentration was not associated with time since the last dose, body weight, or perinatal transmission. CONCLUSION: Oral intrapartum ZDV was feasible and well tolerated. Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration. Although concentrations were not associated with perinatal transmission, these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective.