Longitudinal study on Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine.

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are all potentially pathogenic, which frequently colonize the nasopharynx (NP) prior to causing disease. We studied bacterial NP-colonization in 321 HIV-infected and 243 HIV-uninfected children vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7) at 6, 10 and 14 weeks of age. METHODS: HIV-uninfected infants included those born to HIV-uninfected (HUU) and HIV-infected women (HEU); HIV-infected children with CD4+ lymphocyte ≥25% were randomized to initiate antiretroviral therapy immediately (ART-Immed) or when clinically indicated (ART-Def). Nasopharyngeal swabs for bacterial culture were taken prior to each PCV7 dose (Visits 1-3) and at 20, 39, 47 and 67 weeks of age (Visits 4-7). Swabs were cultured by standard methods and pneumococcal serotyping done by the Quellung method. RESULTS: Colonization patterns for pneumococcus, H. influenzae and S. aureus did not differ between HUU and HEU children; and were also generally similar between ART-Def and ART-Immed children. Prevalence of PCV7-serotype colonization was similar between HIV-infected and HIV-uninfected children, however, overall pneumococcal and specifically non-vaccine serotype colonization tended to be lower in HIV-infected children. HIV-infected children also had a 44% lower prevalence of S. aureus colonization at Visit-1 (p=0.010); and H. influenzae colonization was also lower among HIV-infected than HIV-uninfected children at Visit-2, Visit-3, Visit-6 and Visit-7. CONCLUSION: Vaccine-serotype colonization is similar in PCV-immunized HIV-infected and HIV-uninfected children. We, however, identified a lower prevalence of overall-pneumococcal and H. influenzae colonization in HIV-infected children post-PCV vaccination, the clinical-relevance of which warrants further study.

Immunogenicity following the first and second doses of 7-valent pneumococcal conjugate vaccine in HIV-infected and -uninfected infants.

BACKGROUND: The immunogenicity of pneumococcal conjugate vaccine (PCV) has not been evaluated in HIV-infected infants following the first and second PCV-doses. We studied antibody kinetics of serotypes included in 7-valent PCV in HIV-infected and HIV-uninfected infants prior to and following each of three PCV-doses. METHODS: HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU); and perinatal HIV-infected children with CD(4+)<25% randomized to initiate antiretroviral treatment (ART) when clinically and/or immunologically indicated (ART-) or immediately (ART+) were enrolled. Vaccination occurred at approximately 7.4, 11.5 and 15.5 weeks of age. Serotype-specific antibody was measured by ELISA following each PCV-dose and opsonophagocytic activity (OPA) to three serotypes following the second and third doses. RESULTS: Pre-vaccination, antibody geometric mean concentrations (GMCs) were higher in HUU compared to HIV-exposed groups for most serotypes. GMCs and proportion of infants with antibody ≥0.35 µg/ml were similar in HUU compared to other groups following the second PCV-dose. In all groups, GMCs were greater following the third compared to post-second dose; and a higher proportion within each group had antibody ≥0.35 µg/ml to 6B and 23F. OPA GMTs increased after the third compared to post-second dose for studied-serotypes; as did the proportion with OPA ≥8 to 23F. CONCLUSION: A two-dose primary-series of PCV probably confers similar protection against invasive pneumococcal disease in HIV-infected compared to HUU children. The inferior response to serotypes 6B and 23F, and lower GMCs and OPA GMTs, following two compared to after three PCV-doses may have implications in the prevention of pneumococcal disease in high-burden countries.

Pilot study on the immunogenicity of paired Env immunogens from mother-to-child transmitted HIV-1 isolates.

Recent studies have reported that founder viruses play unique roles in establishing HIV-1 infection. Understanding the biological and immunological features of envelope glycoproteins (Env) from such viruses may facilitate the development of effective vaccines against HIV-1. In this report, we evaluated the immunogenicity of gp120 immunogens from two pairs of clade B and two pairs of clade C mother-to-child transmitted (MTCT) HIV-1 variants that had various levels of sensitivity to broadly neutralizing monoclonal antibodies. Individual gp120 DNA and protein vaccines were produced from each of the eight MTCT Env antigens included in the current study. Rabbits were immunized with these gp120 immunogens by the DNA prime-protein boost approach. High level Env-specific antibody responses were elicited by all MTCT gp120 immunogens. However, their abilities to elicit neutralizing antibody (NAb) responses differed and those from relatively neutralization-resistant variants tended to be more effective in eliciting broader NAb. Results of this pilot study indicated that not all MTCT Env proteins have the same potential to elicit NAb. Understanding the mechanism(s) behind such variation may provide useful information in formulating the next generation of HIV vaccines.

Effect of HIV infection status and anti-retroviral treatment on quantitative and qualitative antibody responses to pneumococcal conjugate vaccine in infants.

Serotype-specific antibody concentration and opsonophagocytic activity (OPA) were evaluated after 3 doses of pneumococcal conjugate vaccine. Groups included human immunodeficiency virus (HIV)-positive infants with CD4(+) cell percentages > or =25% who initiated immediate antiretroviral treatment (the HIV+/ART+ group) or whose antiretroviral treatment was deferred until clinically or immunologically indicated (the HIV+/ART- group). Immune responses were also evaluated in HIV-noninfected infants born to HIV-seronegative (M-/I-) or HIV-positive mothers (M+/I-). Antibody concentrations were similar between HIV+/ART+ and HIV+/ART- infants. However, antibody concentrations were lower in M-/I- infants than in M+/I- infants. Nevertheless, M-/I- infants had superior OPA responses, compared with those in HIV+/ART+ infants, who in turn had better OPA responses, compared with those in HIV+/ART- infants.

Antiviral activity of nucleoside analogues during short-course monotherapy or dual therapy: its role in preventing HIV infection in infants.

BACKGROUND: This is the first report on the preliminary efficacy of 4 different short-course nucleoside analogue regimens (stavudine [d4T], didanosine [ddI], d4T+ddI, and zidovudine [ZDV]) for the prevention of mother-to-child transmission of HIV-1 (MTCT) in a resource-limited setting. DESIGN: This prospective open-label, randomized 4-arm study (May 1999 to May 2000) conducted in South Africa enrolled 373 women from 34 weeks of gestation; medication was continued through delivery and for 6 weeks to infants. MTCT rates were ascertained at birth, 6, 12, and 24 weeks of age. RESULTS: Mean maternal HIV-1 RNA levels decreased rapidly on treatment in all groups. At week 4, the mean decrease was 1.91 log10 copies/mL (c/mL) in the d4T+ddI group, 1.33 log10 c/mL in the ddI group, 1.12 log10 c/mL in the d4T group, and 0.76 log10 c/mL in the ZDV group. Among the 362 evaluable mother-infant pairs, 11 infants in the d4T group, 10 in the ddI group, 5 in the ZDV group, and 4 in the d4T+ddI group were infected by 24 weeks of age. Eleven infections occurred in utero. Treatment with d4T and ddI was not associated with lactic acidosis or hepatic steatosis. CONCLUSIONS: The abbreviated use of nucleoside analogues for the prevention of MTCT appears safe and effective.

Tolerance and safety of different concentrations of chlorhexidine for peripartum vaginal and infant washes: HIVNET 025.

BACKGROUND: There is a continuing need to evaluate sustainable interventions for prevention of mother-to-child transmission (MTCT) of HIV type 1. We evaluated different concentrations (0.25%, 1%, and 2%) of chlorhexidine (CHX) for perinatal maternal and infant washes to identify the maximum tolerable concentration of CHX for such an intervention. METHODS: Women were enrolled during their third trimester at the maternity unit of the Chris Hani Baragwanath Hospital in Soweto, South Africa, and perinatal maternal and infant washes were completed. Subjective maternal symptoms as well as infant examinations were used to assess tolerability of the washes. RESULTS: The 0.25% concentration of CHX was well tolerated by the mothers (n = 29). Ten of 79 women (13%) with 1% CHX washes complained of mild vaginal area burning or itching, and washes were stopped in 5 (6%). Twenty-three of 75 women (31%) in the 2% CHX wash group had subjective complaints, and the washes were stopped in 12 (16%). There were no clinical indications of toxicity of the CHX washes among infants. CONCLUSION: A 1% solution of CHX appears to be a safe and tolerable concentration of CHX for consideration in an MTCT prevention trial.