The magnitude of loss to follow-up of HIV-exposed infants along the prevention of mother-to-child HIV transmission continuum of care: a systematic review and meta-analysis

Introduction: Although prevention of mother-to-child HIV transmission (PMTCT) programs are widely implemented, many children do not benefit from them because of loss to follow-up (LTFU). We conducted a systematic review to determine the magnitude of infant/baby LTFU along the PMTCT cascade. Methods: Eligible publications reported infant LTFU outcomes from standard care PMTCT programs (not intervention studies) at any stage of the cascade. Literature searches were conducted in Medline, Embase, Web of Knowledge, CINAHL Plus, and Maternity and Infant Care. Extracted data included setting, methods of follow-up, PMTCT regimens, and proportion and timing of LTFU. For programs in sub-Saharan Africa, random-effects meta-analysis was done using Stata v10. Because of heterogeneity, predictive intervals (PrIs; approximate 95% confidence intervals of a future study based on extent of observed heterogeneity) were computed. Results: A total of 826 papers were identified; 25 publications were eligible. Studies were published from 2001 to 2012 and were mostly from sub-Saharan Africa (three were from India, one from UK and one from Ireland). There was extensive heterogeneity in findings. Eight studies reported on LTFU of pregnant HIV-positive women between antenatal care (ANC) registration and delivery, which ranged from 10.9 to 68.1%, pooled proportion 49.08% [95% confidence interval (CI) 39.6–60.9%], and PrI 22.0–100%. Fourteen studies reported LTFU of infants within 3 months of delivery, range 4.8–75%, pooled proportion 33.9% (27.6–41.5), and PrI 15.4–74.2. Children were also lost after HIV testing; this was reported in five studies, pooled estimate 45.5% (35.9–57.6), PrI 18.7–100%. Programs that actively tracked defaulters had better retention outcomes. Conclusion: There is unacceptable infant LTFU from PMTCT programs. Countries should incorporate defaulter-tracking as standard to improve retention

Interleukin-6 and granulocyte macrophage-csf in the cerebrospinal fluid from hiv infected subjects with involvement of the central nervous system

We detected the cytokines interleukin-6 (IL-6) and granulocyte macrophage-CSF (GM-CSF) by ELISA in the CSF and serum of 30 HIV-infected patients classified as AIDS dementia complex (ADC), and 20 subjects with other neurological diseases (OND). We have found a high incidence of detectable IL-6 and GM-CSF in the CSF of ADC patients compared with OND patients. No statistical differences were observed between both groups for serum IL-6 and GM-CSF levels. These results suggest an intrathecal synthesis of these cytokines and a possible involvement in the pathogenesis of ADC

Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4(+) cell counts of between 200 and 750 cells per mm(3). Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4(+) cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients

Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen

Background Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, may be the infectious cause of KS. Its prevalence in the general population, on the basis of detection of the virus genome, is controversial. To investigate the seroprevalence, we measured antibodies to a recombinant capsid-related (lytic cycle) KSHV antigen and a latent antigen complex. Methods We selected potentially immunoreactive capsid-related proteins of KSHV by expressing them as recombinant proteins and testing them in western blot assays. We used a truncated recombinant protein encoded by KSHV open reading frame 65 (orf 65) to develop a diagnostic enzyme-linked immunosorbent assay (ELISA) and tested sera from HIV-infected individuals with KS, HIV-uninfected patients with ‘’classic” KS, other HIV risk groups, and blood donors. We also compared the antibody response to this capsid-related protein to the response to latent antigen(s) in an immunofluorescence assay. Findings 77/92 (84%) sera from KS patients reacted with the KSHV orf 65 protein and 84/103 (81 . 5%) reacted with KSHV latent antigen(s). The dominant immunogenic region of orf 65 is within the carboxyterminal 80 aminoacids, a region with little sequence similarity to the related Epstein-Barr virus, suggesting that orf 65 is a KSHV specific antigen. Only three sera from patients with haemophilia (1/84) or from intravenous drug users (2/63) had KSHV specific antibodies in the orf 65 assay whereas none of these sera reacted with latent antigen. Antibodies to KSHV were also infrequently found in UK and US blood donors by either assay (UK, 3/174 with orf 65 and 4/150 with latent antigen; US, 6/117 with orf 65 and 0/117 with latent antigen). They were more common among HIV-infected gay men without KS (5/16 by orf 65 ELISA, 10/33 by IFA), HIV-uninfected STD clinic attenders (14/166 by IFA), and Ugandan HIV-uninfected controls (6/17 by orf 65 ELISA, 9/17 by IFA). Antibody reactivity to the orf 65 protein (ELISA) and to latent antigen(s) (IFA) was concordant in 89% of 462 sera tested but reactive blood donor sera were discordant in both assays. Four AIDS-KS sera were unreactive in both assays. Interpretation The distribution of antibodies to both a capsid-related recombinant protein and latent antigen(s) of KSHV strongly supports the view that infection with this virus is largely confined to individuals with, or at increased risk for, KS. However, infection with KSHV does occur, rarely, in the general UK and US population and is more common in Uganda. Antibodies to latent antigen(s) or to orf 65 encoded capsid protein will not detect all cases of KSHV infection, and a combination of several antigens will probably be required for accurate screening and confirmatory assays