Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004

OBJECTIVE: To estimate the global and regional distribution of HIV-1 subtypes and recombinants in 2004. DESIGN: A study was conducted in which molecular epidemiological data on HIV-1 subtype distribution in individual countries were combined with country-specific estimates of the number of people living with HIV. METHODS: HIV-1 subtype data were collected for 23 874 HIV-1 samples from 70 countries, which together accounted for 89% of all people living with HIV worldwide in 2004. The proportions of HIV-1 infections due to various subtypes detected in each country were combined with the number of HIV infected people in the respective countries to generate regional and global HIV-1 subtype distribution estimates. RESULTS: Subtype C accounted for 50% of all infections worldwide in 2004. Subtypes A, B, D and G accounted for 12%, 10%, 3% and 6%, respectively. The subtypes F, H, J and K together accounted for 0.94% of infections. The circulating recombinant forms CRF01_AE and CRF02_AG each were responsible for 5% of cases, and CRF03_AB for 0.1%. Other recombinants accounted for the remaining 8% of infections. All recombinant forms taken together were responsible for 18% of infections worldwide. CONCLUSION: Combining data on HIV-1 subtype distribution in individual countries with country-specific estimates of the number of people living with HIV provided a good method to generate estimates of the global and regional HIV-1 genetic diversity in 2004. The results could serve as an important resource for HIV scientists, public health officials and HIV vaccine developers.     

Detection of HIV-1 neutralizing antibodies by a simple, rapid, colorimetric assay

A rapid, simple, reproducible and semi-quantitative assay to measure neutralizing antibodies has been developed. It employs a unique cell line which is exquisitively sensitive to infection with all HIV isolates tested. The assay is amenable to microtiter formulation as well as analysis by automation.     

Increase of non-B subtypes and recombinants among newly diagnosed HIV-1 native Spaniards and immigrants in Spain

Although HIV-1 clade B variants are predominant in Western Europe, non-B subtypes are rapidly spreading, mainly due to immigration from endemic regions. All newly diagnosed HIV-1-infected individuals at a HIV/AIDS clinic in Madrid from 2000 to 2007 were identified. Subtype assignment was based on phylogenetic analysis of pol sequences from plasma specimens collected at first visit. A total of 1,430 newly diagnosed HIV-1 individuals were identified: 902 Spaniards, 232 South Americans, and 162 Africans, among others. The proportion of South-Americans and Africans among diagnosed HIV-1 patients increased from 2000 to 2007 (from 17% to 22% and from 4% to 21%, respectively). Half of diagnosis of HIV-1 in 2007 was in foreigners whereas in previous years Spaniards were predominant. Non-B variants were found in 157 (24%) of the 649 subjects who could be subtyped: 11A, 6C, 2D, 1F2, 13G, 4H, 1J, 3CRF01_AE, 64CRF02_AG, 2CRF03_AB, 3CRF06_cpx, 3CRF10_CD, 7CRF11_cpx, 9CRF12_BF, 9CRF14_BG, 1CRF18_cpx, 1CRF19_cpx, 2CRF31_BC, 10 URF and 5 outgroups. They represented 93%, 14% and 4% of newly-diagnosed HIV-1 Africans, South-Americans and native Spaniards, respectively. Non-B subtypes increased from 9% in 2000 to 32% in 2007, specially among South-Americans (from 11% to 20%) and native Spaniards (from 4% to 10%). Most (75%) were recombinant viruses. The highest number and diversity of HIV-1 variants among natives was observed in 2007. HIV-1 non-B subtypes are increasingly present among newly diagnosed HIV-1 individuals in Madrid, representing a third of cases in 2007, whereas 10% of newly diagnosed HIV-1 native Spaniards had non-B viruses.     

Molecular epidemiology of dual HIV-1/HIV-2 seropositive adults from Senegal,West Africa

Dual infection with HIV-1 and HIV-2 can occur in locales where these viruses co-circulate, most commonly in West Africa. Although dual seropositivity is common in this region, the true rate of dual infection remains unclear. In addition, whether unique HIV-1 subtypes are circulating in dually infected individuals is unknown. A cohort of 47 HIV-1 and HIV-2 dually seropositive individuals from Senegal, West Africa was screened for the presence of HIV-1 and HIV-2 gag and env PBMC viral DNA sequences using PCR. Of the 47 dual HIV-1/HIV-2 seropositive individuals tested, 19 (40.4%) had infection with both HIV-1 and HIV-2 confirmed by genetic sequence analysis, whereas only HIV-1 or HIV-2 was confirmed in 17 (36.2%) or 9 (19.1%), respectively. The majority of HIV-1 subtypes found were CRF-02 and A, although subtypes D, C, G, J and B were also found, reflecting the subtypes known to be circulating in Senegal. There was no significant difference in HIV-1 subtype distribution between individuals with confirmed dual infection and patients in this study with dual seropositivity but lacking HIV-2, or with HIV-1 infected patients within the general population in Senegal, although the study was underpowered to detect anything but large differences. The prevalence of HIV-1/HIV-2 dual infection appears to be significantly less than that of dually seropositive individuals and this likely reflects cross-reactive serology. The common HIV-1 subtypes prevalent in West Africa (CRF-02 and subtype A) have a similar distribution to those found in our cohort of dually infected and dually seropositive subjects.     

Retinal manifestations of HIV-1 and HIV-2 infections among hospital patients in The Gambia, West Africa

BACKGROUND: In developed countries, 50-75% of AIDS patients develop retinal complications and about 20-40% acquire cytomegalavirus (CMV) retinitis. We conducted a cross-sectional survey to determine prevalence of these in The Gambia where both HIV-1 and HIV-2 infection are present and the prevalence of HIV-1 is rising. METHOD: All patients attending hospital whose percentage CD4+ cells (CD4%) was below 14, the level associated typically with an AIDS diagnosis, and one half of those whose CD4% was 14 or above were asked to join the study. Fifty-six HIV-1, 52 HIV-2 and 12 dually infected patients were recruited. Photographs of the fundi were taken and interpreted independently. The findings were related to the patients' percentage CD4+ cells. RESULTS: The CD4% was < 14 in 40 patients and < 7 in 17 patients. Thirty-six patients were male. No cases of CMV retinitis were found. Four patients whose CD4% were 4, 5, 11 and 23 had cotton wool spots ranging in number from 1 to 14 for any one patient. The prevalence of cotton wool spots was 8% (95% CI, 0-16%) among patients with CD4% below 14 and 12% (95% CI, 0-27) among patients with CD4% below 7. One of the 4 patients had associated microaneurysm and blot haemorrhages typical of more advanced HIV microvasculopathy. CONCLUSION: CMV retinitis is less common in The Gambia than in developed countries. Non-infectious retinopathy may also be less common.     

Primary resistance mutations to fusion inhibitors and polymorphisms in gp41 sequences of HIV-1 non-B subtypes and recombinants

Primary resistance mutations to fusion inhibitors and polymorphisms in gp41 sequences of non-B subtypes and recombinant HIV-1 isolates were analysed. L91H to RPR103611 was detected in one DGpol/Denv/Dgp41 recombinant; L9F and K144R, rarely reported previously, were frequent in the B region of CRF14_BG recombinants. V194I and V318A, not described in the G subtype, were detected in the G region of BG recombinants and in G subtype viruses that also show the rare mutations T115L, M118V and K90R.     

Full-length genome analysis of HIV-1 subtype C utilizing CXCR4 and intersubtype recombinants isolated in South Africa

The HIV-1 epidemic in South Africa is largely due to subtype C viruses, which preferentially use CCR5 as a coreceptor for infection. We describe full-length genome sequences of two CXCR4-utilizing HIV-1 subtype C viruses and two intersubtype recombinants from South Africa. Three of the viruses (99ZACM4, 99ZACM9, and 99ZASW7) were isolated in 1999 from AIDS patients in Johannesburg, and a fourth virus (98ZADu178) was isolated in Durban in 1998 from an asymptomatic female sex worker. Isolates 99ZASW7 and 99ZACM9 from Johannesburg were subtype C throughout the genome, 99ZASW7 used the CXCR4 coreceptor, and 99ZACM9 used both CCR5 and CXCR4. Isolate 98ZADu178 from Durban was a novel recombinant between subsubtype A2 and subtype C. The third isolate from Johannesburg, 99ZACM4, was a complex, novel recombinant with multiple breakpoints and contained segments of subtypes A, C, D, G, and K. These results establish the presence of intersubtype recombinants in South Africa, indicating that ongoing surveillance for other subtypes and recombinants is necessary.     

Detection of HIV-1-infected cells from patients using nonisotopic in situ hybridization

We have demonstrated that a sensitive, nonisotopic in situ hybridization (ISH) assay can be used to detect HIV-infected cells from seropositive, asymptomatic individuals. Our assay is based on the detection of a biotinated HIV DNA probe hybridized to human immunodeficiency virus (HIV)-infected peripheral blood lymphocytes (PBL) using streptavidin and alkaline phosphatase to identify positive cells. This assay is rapid in that it can be performed within a day and is sensitive enough to unambiguously identify a rare, single, positive cell. Patient samples derived from HIV-seropositive hemophiliacs and HIV-seropositive infants were analyzed before and after coculture with normal PBL. The same samples were investigated using a Dupont P24 antigen-capture kit. It was found that ISH always detected the same positive samples as antigen capture, often in shorter times of coculture. In situ hybridization detected over half of our HIV-infected hemophilia patient population as virus positive, whereas the antigen capture assay detected less than one fourth as virus positive. In situ hybridization detected positive cells directly, without coculture, in 12 out of 35 (34%) hemophiliacs and in three out of eight (37%) infants. The speed, sensitivity, and confidence of ISH and nonisotopic detection indicates that it will be useful as a tool for clinical research and diagnosis.     

Frequency of HIV-1 dual subtype infections, including intersubtype superinfections, among injection drug users in Bangkok, Thailand

OBJECTIVES: To estimate the frequency and incidence of dual HIV-1 subtype infections, including superinfections, among recent seroconvertors from a cohort of injection drug users (IDUs). METHODS: A total of 1209 HIV-negative IDUs were followed in a prospective cohort study at 15 methadone clinics in Bangkok, Thailand. After 2308 person-years (PY) of follow-up, 133 seroconverted to HIV-1, of which approximately 20% were subtype B and 80% were CRF01_AE (formerly called subtype E). Specimens from 126 individuals were available at time of first seropositive test and specimens from 80 of these 126 individuals were also available more than 12 months later. For each infected participant, we calculated the amount of time to superinfection, loss to follow-up, or to the closest visit more than 12 months after the time of initial seropositivity. RESULTS: Of all 126 seroconverters seen at the time of the first seropositive test result, there was no apparent case of concurrent dual subtype infection detected despite 2301 PY of observation. Overall, the incidence of superinfection was 2.2 per 100 PY [95% confidence interval (CI), 0.3-7.8]. The 1-year incidence of CRF01_AE superinfection following subtype B primary infection was 3.9 per 100 PY (95% CI, 0.1-21.9) and the incidence of subtype B superinfection following CRF01_AE primary infection was 1.5 per 100 PY (95% CI, 0.04-8.3). CONCLUSIONS: Determination of the frequency and incidence of dual HIV-1 subtype infection demonstrates that HIV-1 superinfection is not uncommon in a population with high HIV-1 incidence with more than one circulating strain.     

河南省人免疫缺陷病毒流行株的基因亚型分析

目的　研究流行于河南省献血员中的人免疫缺陷病毒（ＨＩＶ） 外膜蛋白（ｅｎｖ） 基因亚型。方法　提取ＨＩＶ 感染者外周血单个核白细胞（ＰＢＭＣ） 的ＤＮＡ,经套式聚合酶链反应（ＮｅｓｔｅｄＰＣＲ） 扩增ｅｎｖ 基因片断,对Ｃ２Ｖ３ 区３５０ ～４５０ 核苷酸顺序进行测定和分析。结果　２０ 份样品的ｅｎｖ 基因序列与Ｂ亚型最为接近,基因离散率为８ ．３４ ％ ,与其它国际亚型的基因离散率在２０ ％ 以上;与流行于云南的Ｂ 亚型毒株基因离散率为４ ．１８ ％ ;样品间的基因离散率为３ ．４ ％ 。结论　流行于河南省献血员中的ＨＩＶ 属Ｂ亚型,并与云南的流行株密切相关;其在河南的流行时间在３ ～６ 年间。     

HIV-1 CRF_BC recombinants infection in China: molecular epidemic and characterizations

CRF_BC recombinant strains were first identified in China and are one of the most prevalent and characteristically unique HIV-1 subtypes across China. Here we aim to review the published data about HIV-1 CRF_BC recombinant strains epidemic in China and to characterize the genetics, biology and drug resistance of this virus. This study may help to better understand the current situation of HIV-1 CRF_BC prevalence and facilitate the development of vaccines and more efficient anti-HIV-1 regimens in China.     

Prevalence of HIV-1 in east African lorry drivers

Sixty-eight lorry drivers and their assistants were examined for evidence of infection with HIV-1 because of their association and regular contact with prostitutes. Out of a total of 68 drivers, 24 (35.2%) were serologically found to be HIV-1 positive. Epidemiological evidence demonstrated a wide travel history involving seven different countries served by the port of Mombasa. History of other sexually transmitted disorders were significantly higher in HIV-seropositive individuals. The data presented here further support the hypothesis that a major route of heterosexual transmission of HIV in Africa is dissemination through a group such as lorry drivers and their assistants, whose behaviour puts them at risk of acquiring sexually transmitted diseases.     

High prevalence of HIV-1, HIV-2 and other sexually transmitted infections among women attending two sexual health clinics in Bissau, Guinea-Bissau, West Africa

The objective was to examine the prevalence of HIV-1, HIV-2 and 10 other sexually transmitted infections (STIs), and to explore the relationship between HIV and those STIs in women attending two sexual health clinics in Bissau, Guinea-Bissau. In all, 711 women with urogenital problems were included. Clinical examination was performed and HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-1, HTLV-2 and syphilis were diagnosed by serology. Trichomonas vaginalis was examined using wet mount microscopy. Cervical samples (and swabs from visible ulcers, if present) were used for polymerase chain reaction (PCR) diagnosis of Chlamydia trachomatis, Mycoplasma genitalium, Haemophilus ducreyi, herpes simplex virus (HSV)-1 and HSV-2, and culture diagnosis of Neisseria gonorrhoeae. The prevalence of HIV-1, HIV-2, and HIV-1 and HIV-2 (dual infection) was 9.5%, 1.8% and 1.1%, respectively. The prevalence of HTLV-1 was 2.8%, HTLV-2 0%, HSV-1 1.4%, HSV-2 7.7%, T. vaginalis 20.4%, syphilis 1.0%, N. gonorrhoeae 1.3%, H. ducreyi 2.7%, M. genitalium 7.7% and C. trachomatis 12.6%. HIV-1 and/or HIV-2 infection was significantly associated with active HSV-2 and HIV-1 was significantly associated with M. genitalium infection. In conclusion, HIV-1 and HIV-2 prevalence was higher compared with previous studies of pregnant women in Guinea-Bissau. The prevalence of co-infection of HIV and other STIs is high. National evidence-based guidelines for the management of STIs in Guinea-Bissau are essential.