Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials.

BACKGROUND: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. METHODS: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. FINDINGS: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). INTERPRETATION: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. FUNDING: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

Fine-needle aspiration cytology in tuberculous lymphadenitis of patients with and without HIV infection.

A study of the cytologic features and role of fine-needle aspiration cytology (FNAC) in tuberculous lymphadenitis (TBL) of 21 patients with HIV (group 1) and 21 patients without HIV (group 2) infection was undertaken. Four cytologic patterns were observed, of which necrotizing lymphadenitis (42.9%) and necrotizing suppurative lymphadenitis (28.6%) were predominant in group 1 while necrotizing granulomatous lymphadenitis (47.7%) and granulomatous lymphadenitis (23.8%) were more common in group 2. No pattern was found specific for either group. Zeihl-Neelsen-stained cytology smears of group 1 showed a much higher percentage of positively (61.9%) and a higher density of acid-fast bacilli than group 2. Definitive diagnoses of TBL on FNAC could be provided in 61.9% of group 1 as against 9.5% of group 2. The need for culture or biopsy for definitive diagnosis was higher in group 2. In suspected TBL, diagnostic efficacy can be improved and the need for surgical biopsy reduced if material collected on FNA is also used for culture.

Multi-drug resistant Acinetobacter ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) due to a multi-drug resistant (MDR) Acinetobacter is one of the most dreadful complications, which occurs in the critical care setting. AIMS AND OBJECTIVES: To find out the incidence of Acinetobacter infection in VAP cases, to determine various risk factors responsible for acquisition of Acinetobacter infection and to determine the antimicrobial susceptibility pattern of Acinetobacter. MATERIALS AND METHODS: A total of 60 endotracheal aspirate specimens from intubated patients diagnosed clinically and microscopically as VAP were studied bacteriologically. All clinical details and prior exposure to antibiotics were recorded. RESULTS: An incidence of 11.6% of Acinetobacter VAP cases was recorded. Various underlying conditions like head injury, cerebral hemorrhage and chronic obstructive pulmonary disease (COPD) were found to be associated with Acinetobacter VAP. Acinetobacter strains exhibited MDR pattern. CONCLUSION: Strict infection control measures, judicious prescribing of antibiotics, antibiotic resistance surveillance programs and antibiotic cycling should be adopted to control infections due to these bacteria in patients admitted to intensive care units.

Acinetobacter septicemia in neonates admitted to intensive care units.

BACKGROUND: Acinetobacter species are gaining importance as potential pathogens in neonatal septicemia because of their frequent isolation and multidrug resistance. AIMS AND OBJECTIVES: The aim of the present study was to evaluate the role of Acinetobacter spp. as important pathogens in neonatal blood stream infection, to identify the associated risk factors, and to evaluate the drug sensitivity pattern. MATERIALS AND METHODS: Blood samples of infected neonates were studied bacteriologically. Cases of Acinetobacter septicemia were identified. Speciation of Acinetobacter species was done. Various risk factors were identified. The drug-sensitivity test was done. RESULTS: A total of 26 Acinetobacter septicemia cases were identified by blood culture. Acb complex strains predominated. Institutional birth and preterm birth were identified as the most frequent significant risk factors. 11.3% mortality rate was recorded. Acb complex strains exhibited a multi-drug resistant pattern. No carbapenem resistance was observed. CONCLUSION: Acinetobacter should be added to the list of organisms causing severe nosocomial infection in neonatal intensive care units. Continuous bacteriological surveillance, implementation of infection control policies, careful disinfection of intensive care equipment, and rational antibiotic use are required for control of such infections.

Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants.

BACKGROUND: Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life. METHODS/FINDINGS: Standard population sequencing and cloning for viral subpopulations present at > or =5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission. CONCLUSIONS/SIGNIFICANCE: Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00061321.