Point of View: Interpreting and dismissing the relevance of the “wait and wipe” finding from the circumcision studies conducted in Africa

Some of the secondary findings from the circumcision studies conducted in Africa, are both interesting and difficult to explain. This paper focuses on the finding that uncircumcised men who waited for ten minutes after sexual  intercourse and then wiped their penises using a dry cloth, had lower rates of HIV infection compared to those who cleaned using a wet cloth or those who cleaned within three minutes of having intercourse. The paper also focuses on the finding on men who became infected and yet they reported no sexual acts or 100% condom use. Interpretations that have been provided so far in trying to explain these two interesting findings are somewhat inadequate. Because of the inadequate interpretation that has been provided, anti-circumcision lobbyist are presenting the “wait and wipe strategy” as an alternative to circumcision for HIV prevention. In this paper, we argue that waiting for ten minutes and wiping with a dry cloth does not prevent men from becoming infected by HIV. We therefore attempt to present some alternative views

Exploring research participants’ perceptions and comprehension of the informed consent process in a pre-exposure HIV prevention study

No abstract available.http://www.retrovirology.com/content/9/S2/P238am2013ay201

HIV-1 vertical transmission in Zimbabwe in 622 mother and infant pairs: rethinking the contribution of Mannose Binding Lectin deficiency in Africa

Vertical transmission of human immunodeficiency virus (HIV) remains a major global health problem. We assessed the association of mannose binding lectin (MBL) deficiency and vertical transmission of HIV. Novel diagnostics would be a major breakthrough in this regard. MBL is a liver-derived protein and a key component of the innate immune system. MBL levels may be classified as normal, intermediate, or deficient in the plasma and can use MBL2 haplotypes as a proxy. These haplotypes comprise polymorphisms in the MBL2 gene and promoter region and are known to result in varying levels of MBL deficiency. MBL deficiency can be defined as presence of A/O and O/O genotypes in the mothers and their children. MBL deficiency leads to defective opsonization activities of the innate immune system and increased susceptibility to several infections, including HIV-1. We determined the prevalence of MBL deficiency, using MBL2 haplotypes among 622 HIV-positive Zimbabwean mothers and their children aged 9-18 months old, in relation to the HIV-1 vertical transmission risk. The median age of the mothers was 30 (26-34, interquartile range [IQR]) years, and the babies' median age was 13 months old at the time of enrollment. From the sample of 622 mothers who were HIV-1 infected, 574 babies were HIV negative and 48 were HIV-1-positive babies, giving a transmission rate of 7.7%. MBL2 normal structural allele A and variants B (codon 5 A>G), C (codon 57 A>G), and promoter region SNPs -550(H/L) and -221(X/Y) were detected. Prevalence of haplotype-predicted MBL deficiency was 34% among the mothers and 32% among the children. We found no association between maternal MBL2 deficiency and HIV-1 transmission to their children. We found no difference in the distribution of HIV-1 infected and uninfected children between the MBL2 genotypes of the mothers and those of the children. Taken together, the present study in a large sample of mother-infant pairs in Zimbabwe adds to the emerging literature and the hypothesis that MBL2 variation as predicted by haplotypes does not influence the vertical transmission risk for HIV. Research from other populations from the African continent is called for to test this hypothesis further.

Longitudinal Analysis of CCR5 and CXCR4 Usage in a Cohort of Antiretroviral Therapy-Naïve Subjects with Progressive HIV-1 Subtype C Infection

HIV-1 subtype C (C-HIV) is responsible for most HIV-1 cases worldwide. Although the pathogenesis of C-HIV is thought to predominantly involve CCR5-restricted (R5) strains, we do not have a firm understanding of how frequently CXCR4-using (X4 and R5X4) variants emerge in subjects with progressive C-HIV infection. Nor do we completely understand the molecular determinants of coreceptor switching by C-HIV variants. Here, we characterized a panel of HIV-1 envelope glycoproteins (Envs) (n = 300) cloned sequentially from plasma of 21 antiretroviral therapy (ART)-naïve subjects who experienced progression from chronic to advanced stages of C-HIV infection, and show that CXCR4-using C-HIV variants emerged in only one individual. Mutagenesis studies and structural models suggest that the evolution of R5 to X4 variants in this subject principally involved acquisition of an "Ile-Gly" insertion in the gp120 V3 loop and replacement of the V3 "Gly-Pro-Gly" crown with a "Gly-Arg-Gly" motif, but that the accumulation of additional gp120 "scaffold" mutations was required for these V3 loop changes to confer functional effects. In this context, either of the V3 loop changes could confer possible transitional R5X4 phenotypes, but when present together they completely abolished CCR5 usage and conferred the X4 phenotype. Our results show that the emergence of CXCR4-using strains is rare in this cohort of untreated individuals with advanced C-HIV infection. In the subject where X4 variants did emerge, alterations in the gp120 V3 loop were necessary but not sufficient to confer CXCR4 usage. © 2013 Jakobsen et al

Longitudinal analysis of coreceptor usage alterations in a cohort of antiretroviral therapy-naïve subjects with progressive HIV-1 subtype C infection

HIV-1 subtype C (C-HIV) is responsible for most HIV-1 cases worldwide. Although the pathogenesis of C-HIV is thought to predominantly involve CCR5-restricted (R5) strains, we do not have a firm understanding of how frequently CXCR4-using (X4 and R5X4) variants emerge in subjects with progressive C-HIV infection. Nor do we completely understand the molecular determinants of coreceptor switching by C-HIV variants. Here, we characterized a panel of HIV-1 envelope glycoproteins (Envs) (n = 300) cloned sequentially from plasma of 21 antiretroviral therapy (ART)-naı¨ve subjects who experienced progression from chronic to advanced stages of C-HIV infection, and show that CXCR4-using C-HIV variants emerged in only one individual. Mutagenesis studies and structural models suggest that the evolution of R5 to X4 variants in this subject principally involved acquisition of an ''Ile-Gly'' insertion in the gp120 V3 loop and replacement of the V3 ''Gly-Pro-Gly'' crown with a ''Gly-Arg-Gly'' motif, but that the accumulation of additional gp120 ''scaffold'' mutations was required for these V3 loop changes to confer functional effects. In this context, either of the V3 loop changes could confer possible transitional R5X4 phenotypes, but when present together they completely abolished CCR5 usage and conferred the X4 phenotype. Our results show that the emergence of CXCR4-using strains is rare in this cohort of untreated individuals with advanced C-HIV infection. In the subject where X4 variants did emerge, alterations in the gp120 V3 loop were necessary but not sufficient to confer CXCR4 usage

Summary of coreceptor usage.

<p>The numbers in parentheses represent the numbers of Env clones that display R5, R5X4 or X4 phenotype as described in the Materials and Methods. Coreceptor usage results for individual Env clones are shown in more detail in . N/A, not available.</p