Molecular epidemiology of HIV in Ghana: dominance of CRF02_AG

Recent studies showed the importance of CRF02_AG in West Africa, although the clinical relevance of these recombinant forms of HIV remains unknown. The present study aimed at determining the molecular diversity of HIV in Ghana and investigating the possible epidemiologic advantage of recombinant HIV-1. Plasma samples collected in 1999-2002 from two populations of HIV infected individuals (144 asymptomatic candidate blood donors and 169 AIDS patients) were studied and 249 of them were molecularly characterised in gag, pol, and env regions. Five molecular groups were identified: strains clustering with CRF02_AG in all regions (147/249 or 59%), recombinant strains clustering with CRF02_AG in one or two regions (50/249 or 20%), other subtypes, pure or recombinant, but not involving CRF02_AG (37/249 or 15%), HIV-2 (11/249 or 4.5%), and double infections (4/249 or 1.5%). There was no significant difference in the distribution of HIV-1 recombinant strains according to clinical presentation. No evidence of a significant increase in CRF02_AG prevalence between 1999 and 2002 was found. Irrespective of clinical condition, CRF02_AG is the predominant molecular form of HIV-1 in Kumasi, Ghana.     

Structural effects of amino acid variations between B and CRF02-AG HIV-1 integrases

HIV‐1 integrase is one of the three essential enzyme required for viral replication and has a great potential as a novel target for anti‐HIV drugs. The sequence variability of the entire integrase (IN) was examined in HIV‐1 subtype B and CRF02‐AG antiretroviral naïve infected patients for the presence of naturally occurring polymorphisms IN gene sequences and protein structures from both subtypes were compared. The phylogenetic analysis showed a total concordance between the 3 pol gene sequences for patients identified as subtype B whereas 3% of patients identified as CRF02‐AG showed a mixture of subtypes. The analysis of IN aa sequences showed that 13 positions (K/R14, V/I31, L/I101, T/V112, T/A124, T/A125, G/N134, I/V135, K/T136, V/I201, T/S206, L/I234, and S/G283) differed between subtypes B and CRF02‐AG. As observed in the 3D model of the preintegration complex, these differences may impact the functional property of IN. The fact that most variations were grouped suggests that some of them are linked together through compensatory mechanisms. This comparison allowed us to identify several variations of amino acids in HIV‐1 IN subtype CRF02‐AG that could have a putative impact on anti‐integrase sensitivity. In particular, the region formed by Thr125, Thr124, Val31 contains at least one residue, T125, which variation has been involved in eliciting resistance to the naphtyridine carboxamide L870,810 IN inhibitor. In conclusion, virological response to anti‐integrase should be studied carefully, according to the subtype, in clinical trials. J. Med. Virol. 80:754–761, 2008. © 2008 Wiley‐Liss, Inc.     

北京市男男性接触者人乳头瘤病毒及人类免疫缺陷病毒感染状况调查

目的 了解北京市男男性接触者人乳头瘤病毒和人类免疫缺陷病毒感染情况,并分析其影响因素.方法 通过男男非政府组织招募志愿者,进行一对一访谈,并开展血清学检测及人乳头瘤病毒DNA分型.结果 被调查的283名男男性接触者,人类免疫缺陷病毒感染率为10.25%,人乳头瘤病毒感染率为70.67%.按照HPV不同感染情况和感染HP...     

我国男男性行为人群HIV-1新发感染者亚型及原发耐药分析

目的为了掌握全国男男性行为人群（MSM人群）HIV原发耐药状况,本研究在BED—EIA新发感染筛查阳性者中开展了亚型及耐药性检测。方法采用同伴推动抽样（简称RDS）或分类滚雪球抽样方法在13个省份男男性行为人群中开展抽样调查,确证阳性者进行BED—EIA检测。通过PCR反应和基因测序对214个新发感染样本进行HIV—1亚型及原发耐药分析。结果扩增成功104个样本,CRF01-AE、CRF07-BC和B’亚型分别占62．5％、28．8％和8．7％;耐药突变发生率20．2％,潜在耐药13个、低度耐药6个,中度耐药4个、高度耐药2个;逆转录酶区耐药突变发生率较高;蛋白酶抑制剂、核苷类反转录酶抑制剂、非核苷类反转录酶抑制剂相关耐药突变发生率分别为7．69％、6．73％及10．6％;耐药发生率14．4％。结论我国MSMHIV新发感染人群中原发耐药问题不容忽视,有必要对MSM人群开展治疗前耐药检测;另外,还需加大感染者管理、加强干预力度,以应对我国MSM人群未来可能的艾滋病治疗原发耐药的严峻考验。     

Early detection of HIV infection and of asymptomatic sexually transmitted infections among men who have sex with men

ObjectiveTo provide data on incidence of early diagnosis of HIV infections and define prevalence and incidence of asymptomatic sexually transmitted infections (STI) in men who have sex with men (MSM).MethodsWe assessed a prospective cohort study of HIV-uninfected MSM at high risk for HIV infection. Participants were selected through a risk-assessment questionnaire, and they were screened for HIV infection (quarterly) and for other STI (yearly): syphilis, and hepatitis A, B and C (serology); Chlamydia trachomatis and Neisseria gonorrhoeae in penis and rectum; and human papillomavirus in anus and mouth (PCR).ResultsBetween November 2009 and October 2012, a total of 258 HIV-uninfected MSM at high risk for HIV infection were included and followed up for a median of 2 years (interquartile range 1.4, 2.5). Nineteen acute HIV infections were diagnosed (incidence, 3.9 per 100 person-years). Prevalence of STI at baseline was follows: syphilis 8.4% (95% confidence interval (CI) 5.4–12.7); hepatitis C virus (HCV) 2.0% (95% CI 0.7–4.8); C. trachomatis in penis 3.2% (95% CI 1.5–6.5) and in rectum 6.5% (95% CI 3.9–10.5); N. gonorrhoeae in penis 2.0% (95% CI 0.8–5.0) and in rectum 6.1% (95% CI 3.6–10.1); human papillomavirus in anal canal 75.7% (95% CI 68.8–81.5) and in mouth 3.8% (95% CI 1.8–7.7).ConclusionsThe implementation of the Check-Ear Project in a MSM community centre allowed for the identification of early HIV infections and asymptomatic STI among MSM. The high incidence of HIV infections and the high prevalence of STI strongly support the recommendation of periodic screenings among sexually active MSM.     

A survey of HIV infection and related high-risk factors among men who have sex with men in Suzhou,Jiangsu,China

A cross-sectional study using the snowball sampling method was conducted in May 2008 to investigate human immunodeficiency virus (HIV) infection status and related high risk factors among men who have sex with men (MSM) in Suzhou city of Jiangsu province. The researchers carried out a face-to-face questionnaire interview among MSM, and collected their blood samples to test for HIV and other sexually transmitted diseases (STDs). Among the 280 respondents, 91.1% had homosexual acts in the past 6 months and 87.5% had multiple homosexual partners; 46.4% had heterosexual sex in the past 6 months and 33.1% had multiple heterosexual partners. The rate of continued condom use was 44.3% in homosexual sex in the past 6 months, while the rate in heterosexual sex was 33.9%. Laboratory test results showed that the prevalences of HIV and syphilis were 7.1% (20/280) and 15.0% (42/280), respectively, but no HCV-positive person was found. In the multivariate logistic regression model, subjects with a monthly income of more than RMB $ 1,000 (OR=4.83,95% CI=1.44-16.22), subjects who often went to bars for sexual partners (OR=2.25, 95%CI=1.21-4.20), and subjects who had more than one sexual partner in the past 6 months (OR=0.49, 95%CI=0.25-0.97) and had sex with fixed sexual partners in the past 6 months (OR=0.42, 95%CI=0.25-0.75) were significantly associated with the rate of continued condom use in homosexual sex in the past 6 months. Unprotected sex and multiple sexual partners were more common among MSM in Suzhou city; furthermore, the prevalences of HIV infection and syphilis were relatively high. HIV preventive measures should be designed to address these risk factors and control the spread of HIV among MSM.     

Oral human papillomavirus type-specific infection in HIV-infected men: a prospective cohort study among men who have sex with men and heterosexual men

The natural history of type-specific oral infection of human papillomavirus (HPV) was assessed in a cohort of HIV-infected men (538 men who have sex with men (MSM); 195 heterosexuals). Risk factors associated with oral HPV infections were examined. The overall prevalence of HPV was 16%: HPV-16 was the most prevalent type (3.7% MSM; 7.8% heterosexuals). The prevalence of HPV-16 in heterosexuals was associated with CD4 nadir counts <200 cells/μL (OR_adjusted = 3.0, 95% CI, 1.4–6.3). The overall incidence of HPV was similar between groups (11%), but the incidence of HPV-16 was higher in heterosexuals (OR_adjusted = 3.2, 95% CI, 1.1–9.5). Not only MSM but also HIV-infected heterosexual men are at risk of HPV infection. Regular and careful oral inspection is needed.     

Hepatitis B vaccination in infants of mothers infected with human immunodeficiency virus

A study was conducted to investigate the immunogenicity of a recombinant DNA hepatitis B vaccine in neonates and children of HIV-infected women. Immunization against hepatitis B consisted of three 10 μg doses of the vaccine administered on a 0-, 1- and 6-month schedule. The children were followed up for an average of 11 months. Of the 118 HIV-positive neonates who participated in the study, 95 lost their HIV antibodies during the follow-up period. Most (94.2%) of the latter who completed the study responded to the vaccine. Of the 23 who remained HIV-positive, 17 completed the study and 7 produced hepatitis B antibodies. © 1995 Wiley-Liss, inc.     

Molecular characterization of hepatitis B virus strains circulating in Belgian patients co-infected with HIV and HBV: overt and occult infection

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) have similar transmission routes, implying that patients infected with HIV are at particular risk for HBV infection. Patients who are co-infected with HIV and HBV progress more rapidly to end-stage liver disease and different HBV genotypes may have a distinct impact on disease progression. One hundred ninety-one anti-HBc-positive sera from Belgian patients co-infected with HIV and HBV were collected during 1998-2008. Full-length HBV genomes as well as large S or partial S genes were amplified and their molecular evolutionary history was analyzed. Clinically, 30 (65.8%) patients were categorized as "overt infection" and 16 (34.7%) cases were categorized as "occult infection." Five distinct HBV genotypes comprising A (69.6%), E (19.6%), followed by D, C, and G were detected. HBV genotype A was observed in all clinical groups and in patients with varying ethnical background. HBV genotype E could be detected in African patients who were mostly infected by heterosexual contacts. Several clinically important mutations at the HBs major hydrophilic region were detected in the new isolates but with no significant difference between occult and overt infection. The high prevalence of HBV genotype A in overt and occult cases, and in particular the detection of certain HBV subgenotypes in patients co-infected with HIV and HBV that carry diagnostic escape mutations, may provide useful information for national guidelines for prophylaxis and treatment.     

Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan

The prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion-transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti-HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)-region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population.     

Differential isotype expression and binding properties of T cell-reactive antibodies in human immunodeficiency virus (HIV) infection

Isotype and binding characteristics of T cell-reactive antilymphocyte antibodies (ALA) were investigated in 287 human immunodeficiency virus (HIV)⁺ sera from patients with CDC II to IVC clinical disease. Using purified soluble T-lymphoblast (CEM cell line) membranes and an ELISA method, 29 HIV⁺ sera showed significant reactions with this substrate and a selective expression of IgG-ALA was detected in 7 HIV⁺ sera. Subsequent microcytotoxicity assays, utilizing peripheral T lymphocytes and CEM cells as targets, demonstrated no significant cytotoxic capability in such sera, whereas 12 of 17 HIV⁺ serum samples with IgM-ALA ELISA reactivities showed a significant degree of killing in the Terasaki test. Further experiments of saturation of CD4 molecules on CEM extract by OKT4 monoclonal antibody (MoAb) induced a high inhibition of IgG-ALA binding to the T-cell membranes in only two IgG-ALA⁺ sera (No. 93, CDC III; No. 179, CDC II stage). Conversely, treatment of CEM membrane lysate with Leu3a MoAb, specific for the gp120 reactive domain of the HIV receptor, failed to prevent membrane binding in all seven of the IgG-ALA⁺ sera. Following the adsorption of serum 93 on a T-cell membrane antigen affinity column, SDS-PAGE analysis demonstrated that the predominant ALA material reacting with T-cell membranes was IgG with no detectable traces of IgM. These data provide evidence that ALA in HIV⁺ patients may be simultaneously or selectively expressed as IgG and/or IgM with different properties. While IgM-ALA show predominant cytotoxic activity, IgG-ALA may include anti-CD4 molecules. However, IgG binding to the C-terminal domain of native HIV receptor appears to occur at a lower rate than IgM-ALA in HIV infection.