Emergence and diversity of different HIV‐1 subtypes in South Africa, 2000–2001

HIV‐1 is a major health problem in South Africa with an average prevalence rate of 29.1% in pregnant women and between 4.9 and 6.1 million people infected. Using env gp120 V3 serotyping and genotyping techniques 410 patient samples were investigated. Most of the samples were obtained from different clinics in the greater Cape Town area of the Western Cape Province in South Africa. These included an academic hospital, state and private clinics, an informal settlement, sex worker cohorts, and the blood transfusion services. RNA was extracted from plasma samples followed by RT‐PCR and sequencing of the env gp120 V3 region. Sequence fragments were assembled using Sequencher V4.7 and subsequently codon aligned. Distance calculation, tree construction methods, and bootstrap analysis were implemented using MEGA version 4.0. Viral load measurements indicated that HIV‐1 RNA levels from 74 samples were below the assay detection limit. Three hundred thirty‐six samples were used for env PCR and sequencing and 320 were assigned to subtypes. The majority of the sequences were subtyped as C (n = 285, 89.0%). Other subtypes detected were subtype A (n = 10, 3.1%); subtype B (n = 22, 6.8%); one each of subtypes F1, G, U, and a CH recombinant. Whether this diversity will have major implications for HIV‐1 evolution and vaccine development in this region remains undetermined. J. Med. Virol. 81:1852–1859, 2009. © 2009 Wiley‐Liss, Inc.     

High level of HIV‐2 false positivity in KwaZulu‐Natal province: A region of South Africa with a very high HIV‐1 subtype C prevalence

Human immunodeficiency virus 2 (HIV‐2) is found predominantly in West Africa. It is not unlikely, however, that HIV‐2 may also be found in South Africa, due to the influx of immigrants into this country. It is important to distinguish between HIV‐1 and HIV‐2 since the clinical courses and treatment responses of these viruses are different. Routine serological methods for diagnosing HIV do not differentiate between HIV‐1 and ‐2 infections, while rapid tests, viral load quantification and PCR are HIV‐type—specific. The objective of this study was to describe the seroprevalence and molecular epidemiology of HIV‐2 in KwaZulu‐Natal, one of the regions with the highest HIV prevalence in the world and home of the two largest harbors in South Africa. HIV‐1 positive samples were screened for antibodies against HIV‐2, using a rapid test. The confirmation of HIV‐2 positive samples was done by PCR. Of the 2,123 samples screened, 319 (15%) were identified as positive by the rapid test. None of these samples were confirmed positive by PCR. To explore this discrepancy in the results, a subset (n = 52) of the rapid HIV‐2 positive samples was subjected to Western blotting. Thirty‐seven (71%) of these were positive, yielding an overall HIV‐2 seroprevalence of 10.6%. Three out of 28 (10.7%) Western blot positive samples were positive by a Pepti‐LAV assay. This discrepancy between serological and molecular confirmation may be attributed to non‐specific or cross‐reacting antibodies. The use of rapid tests and Western blots for HIV‐2 diagnosis in South Africa should be interpreted with caution. J. Med. Virol. 85:2065–2071, 2013. © 2013 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc.     

Immune activation and antibody responses in non‐progressing elite controller individuals infected with HIV‐1

An extremely rare subset of patients infected with HIV‐1 designated as “non‐progressing elite controllers” appears to be able to maintain stable CD4⁺ T‐cell counts and a median plasma viremia below the detection limit of current ultrasensitive assays (<50–80 copies/ml of plasma) for >10 years in the absence of antiretroviral therapy. Lymphocyte subsets (CD4⁺, CD8⁺), immune activation markers (HLA‐DR⁺, CD38⁺, Beta‐2‐microglobulin), and HIV‐specific antibody responses were longitudinally examined in four non‐progressing elite controllers over more than 5 years. Two control groups of seronegative healthy individuals and untreated patients infected with HIV‐1 presenting detectable viremia were also included. None of the non‐progressing elite controllers displayed the high T‐cell activation levels generally seen in the seropositive individuals, keeping them within the normal range. Three non‐progressing elite controllers showed no significant immune system abnormalities when compared to seronegative individuals, displaying a low proportion of HIV‐1‐specific binding antibodies and low avidity index, similar to those observed for individuals infected recently with HIV‐1. One non‐progressing elite controller exhibited CD8⁺ T‐cell counts and β2‐M levels above normal ranges and developed a low but “mature” (high‐avidity) HIV‐1‐specific antibody response. Thus, the non‐progressing elite controllers are able to maintain normal T‐cell activation levels, which may contribute to prevent, or greatly reduce, the damage of the immune system typically induced by the HIV‐1 over time. They are, however, immunologically heterogeneous and very low levels of antigen exposure seem to occur in these patients, sufficient for sustaining a low, but detectable, HIV‐1‐specific immunity. J. Med. Virol. 81:1681–1690, 2009. © 2009 Wiley‐Liss, Inc.     

Novel HIV‐1 clade B candidate vaccines designed for HLA‐B*5101+ patients protected mice against chimaeric ecotropic HIV‐1 challenge

Novel candidate HIV‐1 vaccines have been constructed, which are tailor‐designed for HLA‐B^*5101⁺ patients infected with HIV‐1 clade B. These vaccines employ novel immunogen HIVB‐B^*5101 derived from consensus HIV‐1 clade B Gag p17 and p24 regions coupled to two Pol‐derived B^*5101‐restricted epitopes, which are together with a third B^*5101 epitope in Gag dominant in HIV‐1‐infected long‐term non‐progressing patients. Both plasmid DNA and modified vaccinia virus Ankara (MVA) vectors supported high expression levels of the HIVB‐B^*5101 immunogen in cultured cells. Heterologous DNA prime‐recombinant MVA boost regimen induced efficiently HIV‐1‐specific CD8⁺ T‐cell responses in BALB/c mice. These vaccine‐elicited T cells were multifunctional, killed efficiently target cells in vivo, and protected mice against challenge with ecotropic HIV‐1/NL4‐3 and ecotropic HIV‐1/NDK chimaeric viruses with HIV‐1 clade B or D backbones, respectively, and ecotropic murine leukemia virus gp80 envelope, and therefore did so in the absence of anti‐HIV‐1 gp120 antibodies. These results support further development of HIVB‐B^*5101 vaccines in combined heterologous‐modality regimens. The use of allele‐specific vaccines in humans is discussed in the context of other developments in the HIV‐1 field.