Modelling the impact of HIV prevention and treatment for men who have sex with men on HIV epidemic trajectories in low- and middle-income countries.

Little is known about the impact of combination HIV prevention interventions for men who have sex with men (MSM) and the impacts on the wider epidemics. Modelling analyses of MSM-specific interventions across varied HIV epidemics may inform evidence-based responses. The Goals model was adapted to project the impacts of providing HIV interventions for MSM and access to expanded coverage of antiretroviral therapy (ART) for adults to measure the effects on the MSM and adult epidemics in Peru, Ukraine, Kenya and Thailand. Positive impacts were observed in all four countries. Across epidemics, 14-25% of infections among MSM may be averted between 2012 and 2016 when MSM interventions are brought to scale and MSM have equal access to expanded ART for adults. Among adults, MSM interventions may avert up to 4000 new infections, in addition to the benefits associated with increased ART. Greatest impacts from expanded interventions were observed in countries where same sex transmission contributes significantly to the HIV epidemic. While significant benefits are observed among the adult and MSM populations with expansion of ART, consideration should be given to the synergies of combining ART expansion with targeted interventions to reach hidden, high-risk populations for HIV testing and counselling and linkages to care.

HIV type 1 in Fiji is caused by subtypes C and B.

The HIV epidemic in Fiji remains largely uncharacterized. By February 2009, there were 294 confirmed cases; the majority occurred among the 20- to 39-year old age group and resulted from heterosexual contact. There are currently no published data concerning HIV subtypes in Fiji. In this study, venous blood samples were collected as dried blood spots from 35 HIV-positive individuals in Fiji. HIV-1 subtype was determined for 27 (77%) samples and the presence of four different subtypes, with multiple introductions of two, was demonstrated. Subtype distribution was as follows: 16 (59%) were subtype C, 9 (33%) were subtype B, 1 (4%) was subtype A, and 1 (4%) was subtype G. Phylogenetic analysis showed a clear segregation of the Fijian subtype C isolates and previously published Papua New Guinea subtype C isolates as well as multiple introductions of subtype B. These findings represent the first HIV-1 subtype data from the Fiji Islands.

Survey of reverse transcriptase from the heterosexual epidemic of human immunodeficiency virus type 1 CRF01_AE in Thailand from 1990 to 2000.

Genetic diversity of the HIV-1 envelope gene has shown a steady increase over time in the Thai and other regional epidemics. A serial survey of subtype CRF01_AE polymerase gene (RT) diversity in Thailand was performed, using 48 novel and 15 reported sequences covering the period 1990--2000. These sequences were gathered from individuals whose sole risk factor for infection was heterosexual contact. By contrast to envelope, diversity was low and, despite a 40% increase early in the epidemic, has remained static since 1996. These results indicate that epidemic HIV-1 may be constrained within defined limits of genetic diversity at least in some genomic regions.

Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy.

OBJECTIVE: To determine whether HIV-1 can be recovered from blood monocytes as well as resting, memory CD4 T lymphocytes of patients on highly active antiretroviral therapy (HAART) with undetectable plasma viraemia and whether infection is active or latent. DESIGN: Five patients with plasma HIV-1-RNA levels of less than 500 copies/ml for at least 3 months and less than 50 copies/ml at the time of sampling were initially selected, followed by an additional five patients with viral loads of less than 50 copies/ml for 3 months or more. METHODS: Monocytes were isolated from blood by plastic adherence, then further purified by a second adherence step or CD3 depletion before co-culture with CD8-depleted donor peripheral blood mononuclear cells. Virus isolates were examined for mutations conferring resistance to reverse transcriptase or protease inhibitors and for genotype. The highly purified monocytes were also analysed for the presence of proviral and unintegrated viral DNA and multiply spliced (MS) viral mRNA by polymerase chain reaction. RESULTS: Virus was recovered from monocytes of five patients. Sequencing of the recovered viruses did not reveal multiple drug resistance, and was consistent with a non-syncytium-inducing/CCR5 phenotype. Proviral DNA was detectable in monocytes from all subjects, and unintegrated HIV-1 DNA and MS RNA was found in four out of five populations examined. CONCLUSION: Recovery of replication-competent virus from some HAART patients indicates that monocytes can also harbour HIV-1. Detection of circular, viral DNA and spliced RNA, albeit at very low levels, in these cells suggests that their infection is recent and transcriptionally active rather than latent.

Prevalence of CCR2-64I, SDF1-3'A and CCR5-Delta32 alleles in healthy Thais.

A genetic survey was performed of 200 healthy Thai blood donors for the frequency of three alleles that influence susceptibility to HIV infection and the rate of progression to HIV disease. The CCR5-Delta32 allele was not detected in this population. The CCR2-64I allele was detected at a frequency similar to that found in other Asian populations (15.7%). SDF1-3'A was detected at 33.2%, supporting a cline of increasing frequency of this allele from African and Caucasian to Asian (particularly Australasian) populations. These results have implications for the role of host genetic background in the biology and pathology of HIV in Thailand, and indicate that a systematic survey of non-Caucasian populations may reveal novel alleles important in HIV disease.

Rapid full-length genomic sequencing of two cytopathically heterogeneous Australian primary HIV-1 isolates.

Two Australian HIV-1 isolates, derived from patient blood (HIV(MBC200)) and cerebrospinal fluid (HIV(MBC925)), were characterized after in vitro culture in peripheral blood mononuclear cells (PBMC). Although virus replication was similar, as measured by cell-free reverse transcriptase activity, only one of the two isolates (HIV-1(MCB200)) consistently induced cell syncytia and depleted the PBMC population of CD4+ cells by cell killing. A novel technique, devised for rapidly obtaining high-quality viral sequence data and the full-length genomic sequence of these two isolates, is presented. Analysis of the predicted sequence of the viral Env proteins provides correlates of the observed phenotypes. Phylogenetic analysis derived using near full-length sequence of these and other HIV-1 subtype B genomic sequences (including two other Australian isolates) shows a star-shaped phylogeny with each member having a similar genetic diversity. These data expand the database of genomic sequence available from well-characterized primary clinical isolates of HIV-1 using a novel rapid technique.

The explosive human immunodeficiency virus type 1 epidemic among injecting drug users of Kathmandu, Nepal, is caused by a subtype C virus of restricted genetic diversity.

An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among the injecting drug user population of Kathmandu, Nepal, whose seropositivity rate has risen from 0 to 40% between 1995 and 1997. By using Catrimox to preserve whole-blood RNA at ambient temperature for transportation, HIV-1 envelope V3-V4 sequences were obtained from 36 patients in this group. Analysis of the sequences indicated a homogenous epidemic of subtype C virus, with at least two independent introductions of the virus into the population. Viral diversity was restricted within two transmission subclusters, with the majority of variation occurring in V4. Calculation of the synonymous-to-nonsynonymous mutation ratio (Ks:Ka) across this region showed that significant evolutionary pressure had been experienced during the rapid horizontal spread of the virus in this population, most strongly directed to the region between V3 and V4.

Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort.

BACKGROUND AND METHODS: The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type 1 (HIV-1) with a deletion in the region in which the nef gene and the long terminal repeat overlap. Two recipients have died since 1994, at 77 and 83 years of age, of causes unrelated to HIV infection; one other recipient, who had systemic lupus erythematosus, died in 1987 at 22 years of age of causes possibly related to HIV. We present longitudinal immunologic and virologic data on the six surviving members and one deceased member of this cohort through September 30, 1998. RESULTS: The five surviving recipients remain asymptomatic 14 to 18 years after HIV-1 infection without any antiretroviral therapy; however, the donor commenced therapy in February 1999. In three recipients plasma concentrations of HIV-1 RNA are undetectable (<200 copies per milliliter), and in two of these three the CD4 lymphocyte counts have declined by 9 and 30 cells per cubic millimeter per year (P=0.3 and P=0.5, respectively). The donor and two other recipients have median plasma concentrations of HIV-1 RNA of 645 to 2850 copies per milliliter; the concentration has increased in the donor (P<0.001). The CD4 lymphocyte counts in these three cohort members have declined by 16 to 73 cells per cubic millimeter per year (P<0.001). In the recipient who died after 12 years of infection, the median plasma concentration of HIV-1 RNA was 1400 copies per milliliter, with a decline in CD4 lymphocyte counts of 17 cells per cubic millimeter per year (P=0.2). CONCLUSIONS: After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV-1 RNA. The CD4 lymphocyte counts appear to be stable in the three subjects in whom plasma HIV-1 RNA remains undetectable.

NYK/FLK-1: a putative receptor protein tyrosine kinase isolated from E10 embryonic neuroepithelium is expressed in endothelial cells of the developing embryo.

A protein tyrosine kinase (NYK/FLK-1), bearing all the hallmarks of a growth factor receptor, has been isolated from a cDNA library generated from enriched populations of mouse day 10 embryonic neuroepithelium and from day 18 embryonic colon. Sequence analysis of cDNAs covering the entire coding region of this 5.7 kb mRNA predicted the presence of seven immunoglobulin-like domains in the extracellular region of this molecule. This feature, coupled with the detection of an insert domain bisecting the kinase domain of the predicted protein sequence, places NYK/FLK-1 firmly in the Platelet-derived Growth Factor Receptor-related class of molecules. NYK/FLK-1 is expressed at high levels in adult heart, lung, kidney, brain and skeletal muscle, but is also expressed at lower levels in most other adult tissues. In situ hybridization of day 12.5 embryo sections demonstrated NYK/FLK-1 mRNA expression in endothelial cells lining the dorsal aorta and intervertebral veins. In addition, expression was found in cells lining the capillary plexus which surrounds the developing neuroepithelium, and in the endothelial cells which are found within the embryonic lung, spleen, liver and metanephros.