Table_1.docx

<p>The success of prevention of mother to child transmission programs over the last two decades has led to an increasing number of infants who are exposed to human immunodeficiency virus (HIV), but who are not themselves infected (HIV-exposed, uninfected infants). Although the morbidity and mortality among HIV-exposed, uninfected infants is considerably lower than that among HIV-infected infants, they may remain at increased risk of infections in the first 2 years of life compared with their HIV-unexposed peers, especially in the absence of breastfeeding. There is some evidence of immunological differences in HIV-exposed, uninfected infants, which could play a role in susceptibility to infection. Cytomegalovirus (CMV) may contribute to the increased immune activation observed in HIV-exposed, uninfected infants. Infants born to HIV-infected women are at increased risk of congenital CMV infection, as well as early acquisition of postnatal CMV infection. In infants with HIV infection, CMV co-infection in early life is associated with higher morbidity and mortality. This review considers how HIV infection, HIV exposure, and CMV infection affect infant responses to vaccination, and explores possible immunological and other explanations for these findings. HIV-infected infants have lower vaccine-induced antibody concentrations following tetanus, diphtheria, pertussis, hepatitis B, and pneumococcal vaccination, although the clinical relevance of this difference is not known. Despite lower concentrations of maternal-specific antibody at birth, HIV-exposed, uninfected infants respond to vaccination at least as well as their HIV-unexposed uninfected peers. CMV infection leads to an increase in activation and differentiation of the whole T-cell population, but there is limited data on the effects of CMV infection on infant vaccine responses. In light of growing evidence of poor clinical outcomes associated with CMV infection in HIV-exposed, uninfected infants, further studies are particularly important in this group. A clearer understanding of the mechanisms by which maternal viral infections influence the developing infant immune system is critical to the success of maternal and infant vaccination strategies.</p

Outcome Flow Diagram.

<p>Outcome Flow Diagram.</p

Univariable analysis: psychosocial variables and LTFU.

1<p>n = 380 unless stated;</p>2<p>Cox Regression;</p>3<p>n = 376;</p>4<p>n = 376;</p>5<p>n = 379;</p>6<p>n = 379;</p>7<p>n = 267.</p

Distribution of hypertension by age group in (A) women and (B) men.

<p>Hypertension categories (normal: systolic BP less 120 or diastolic BP less 80 mmHg; stage-I hypertension: systolic BP between 140–160 mmHg and/or diastolic BP between 90–100 mmHg; stage-II hypertension: systolic BP greater 160 mmHg and/or diastolic BP greater than 100 mmHg).</p

Distribution of body mass index by age group in (A) women and (B) men.

<p>BMI categories (underweight: less than 18.5 kg/m²; normal: between 18.5 and 25 kg/m²; overweight: between 25 and 30 kg/m²; obese: greater than 30 kg/m²) .</p

Univariable analysis: demographic and clinical variables and LTFU.

1<p>n = 380 unless stated;</p>2<p>Cox Regression;</p>3<p>n = 356;</p>4<p>n = 363;</p>5<p>n = 377;</p>6<p>n = 377.</p

Anthropometric measurements, body-mass index (BMI), blood pressure, and hypertension staging by HIV infection status and sex.

1<p>Median (interquartile range)</p>2<p>sBP (systolic blood pressure), dBP (diastolic blood pressure)</p>3<p>Stage-I hypertension refers to systolic sBP between 140–160 mmHg and/or dBP between 90–100 mmHg.</p>4<p>Stage-II hypertension refers to sBP greater 160 mmHg and/or dBP greater than 100 mmHg.</p

Flow diagram of individuals participating in the various aspects of the health and demographic surveillance.

<p>Non-contacts refer to eligible individuals who were not contacted due to death, illness or had out-migrated outside the demographic study area.</p

Reduction in early mortality on antiretroviral therapy for adults in rural south africa since change in CD4+ cell count eligibility criteria

Objective: To explore the impact of expanded eligibility criteria for antiretroviral therapy (ART) on median CD4+ cell count at ART initiation and early mortality on ART. Methods: Analyses included all adults (16 years) initiated on first-line ART between August 2004 and July 2012. CD4+ cell count threshold 350 cells per microliter for all adults was implemented in August 2011. Early mortality was defined as any death within 91 days of ART initiation. Trends in baseline CD4+ cell count and early mortality were examined by year (August to July) of ART initiation. Competing risks analysis was used to examine early mortality. Results: A total of 19,080 adults (67.6% female) initiated ART. Median CD4+ cell count at ART initiation was 110-120 cells per microliter over the first 6 years, increasing marginally to 145 cells per microliter in 2010-2011 and more significantly to 199 cells per microliter in 2011-2012. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate was 19.4 per 100 personyears [95% confidence interval (CI) 18.2 to 20.7]. After adjustment for sex, age, baseline CD4+ cell count, and concurrent tuberculosis (TB), there was a 46% decrease in early mortality for those who initiated ART in 2011-2012 compared with the reference period 2008-2009 (subhazard ratio, 0.54; 95% CI: 0.41 to 0.71). Conclusions: Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rate in this primary health care programme. These findings provide strong support for national ART policies and highlight the importance of earlier ART initiation for achieving reductions in HIV-related mortality. Copyright © 2013 by Lippincott Williams & Wilkins

Participation rates among residents aged 15–54years in HIV testing, 2003–6.

<p>Participation rates among residents aged 15–54years in HIV testing, 2003–6.</p