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W2068171898 abstract "Introduction and history In 1985, a group of healthy Senegalese whose sera demonstrated much stronger antibody responses to simian immunodeficiency virus (SIV) than to the HIV type 1 (HIV-1) was first described [1]. In 1986, this new retrovirus was isolated, which is now known as HIV type 2 (HIV-2) [2,3]. Although both HIV-1 and HIV-2 belong to the lentivirus subfamily, and their genomic organization is similar [4], HIV-2 is only about 40% similar to HIV-1 in nucleotide sequence and is more closely related to SIV, with approximately 75% (or greater, see later) nucleotide sequence similarity [4-6]. Although both HIV-1 and HIV-2 can cause acquired immune deficiency syndrome (AIDS), the clinical and biological characteristics of infection with these two viruses show substantial differences, as well as similarities [7]. In particular, HIV-2 is less readily transmitted and is generally less pathogenic than is HIV-1 [8,9]. In this paper, we review what is presently known about HIV-2. Epidemiology The Centers for Disease Control began tracking AIDS in the United States in 1981 [10] and began testing blood donations for the presence of HIV-2 in 1992, after retrospectively testing for the presence of HIV-2 in samples donated from 1987 to 1989 [11,12]. To date, 800 000 Americans have been infected with HIV, the vast majority of these being HIV-1 infections [10]. As of 31 January 2000, the Centers for Disease Control had identified 80 HIV-2-infected individuals in the United States [13]. Infection with HIV-2 was first described in urban settings in Africa [1] and appears to have been present in the area since at least 1966 [14,15]. The prevalence of HIV-2 remains highest in Western Africa and in countries that have socio-economic ties with the area [16]. Thus, moderate to high rates of infection have been found in urban areas of most West African countries, as well as in Angola and Mozambique, which are former Portuguese colonies (reviewed in [16-18]). Portugal, with several former colonies in Western Africa, has the highest incidence of HIV-2 in Europe, with HIV-2 being responsible for 4.5% of all AIDS cases [19]. In one study, greater than 60% of all newly diagnosed HIV-2 infections in Portugal could not be directly traced back to a West African contact, demonstrating its entrenchment in the local population [19]. Tracking the exact prevalence of HIV-2 in Africa remains difficult due to various factors, including a non-stationary population, and differing techniques in the collection and analysis of prevalence data. However, studies suggest that Guinea-Bissau has the highest prevalence of HIV-2 infection [16]. In 1987, in a random sampling of inhabitants of multi-family houses, infection rates for HIV-2 were 8.9% in those persons older than 15 years old and 20% in those older than 40 years old [20]. In Guinnea-Bissau, a prevalence of 13.4% in asymptomatic men has been reported [21]. Studies generally suggest a decreasing prevalence of HIV-2 infection in West Africa: from 1985 to 1996, nine out of 10 nations studied showed decreasing HIV-2 prevalence rates in blood donors (except Nigeria, reviewed in [22]), and from 1988 to 1992, in pregnant women in the Ivory Coast, the prevalence of HIV-2 dropped from 2.6 to 1.5% [23]. However, the decrease in HIV-2 prevalence coincides with an increasing prevalence of HIV-1 infection, which is spreading at a rate much faster than is the drop in HIV-2 prevalence [22,23]. Only very low rates of HIV-2 infection are found outside of West Africa, Portugal, or countries that were previously Portuguese colonies, such as Mozambique and Angola. Between June 1992 and June 1995, 62 people in the United States were reported to have HIV-2 infection. Only three of those were found among blood donors, out of 74 million donations [24]. Most of the HIV-2-infected individuals had clear links to western Africa, either through birth or sexual partners [24]. Seventy-five cases of HIV-2 infection had been reported in France by 1994, with 58 of those being among people who came directly from West Africa [16]. Evolution of HIV-2 Analyses of serological data indicate that HIV-2 and SIV are closely related [1]. All SIV proteins are immunoprecipitated by sera from HIV-2-positive patients [1]. Multiple independent zoonotic transmissions between the primate hosts of different groups of SIV and humans were thus suspected as the ultimate source of HIV-2 infection. Five lines of evidence are used to substantiate zoonotic transmission of SIV into humans: (i) overall similarities in viral genome organization, (ii) phylogenetic relatedness, (iii) geographic coincidence, (iv) prevalence in the natural host, and (v) plausible routes of transmission [25-28]. Thus, evidence that at least some subtypes of HIV-2 came from SIVsm, a lentivirus found in Sooty Mangabey monkeys (Cercocebus atys), comes from their highly similar genomic structure, including the presence of the accessory gene vpx (a gene unique to HIV-2 and SIV). Furthermore, Sooty Mangabeys, like HIV-2, are found in western Africa and have a high prevalence of natural infection with SIVsm, and these monkeys are commonly hunted for food, followed by exposure to potentially infected body fluids and tissues during butchering. Orphan monkeys are often kept as pets, and one study found that, between 1988 and 1989, two out of 25 pet Sooty Mangabeys from West Africa were found to be infected with SIVsm, demonstrating an additional potential route for transmission [29]. In addition, SIVsm and HIV-2 are phylogenetically related. In fact, SIVsm and HIV-2 isolated from the same area are more related to each other than to SIVsm from a different area, and cannot be separated into distinct phylogenetic lineages according to species of origin [30]. SIV and HIV-2 also share a large amount of nucleotide similarity (approximately 75%). In fact, the HIV-2 pol and env gene sequences cluster within SIV lineages, showing that HIV-2 in humans and SIV in mangabeys are members of a single diverse virus family [6,27,30,31]. HIV-2 appears to have emerged from at least seven different zoonotic transmissions of a primate lentivirus to humans, resulting in the seven known subtypes of HIV-2 (A-G) [27,32,33]. Although previously it was believed that HIV-1 and HIV-2 came from a single zoonotic crossover event [4,34], HIV-1 now appears to be a crossover from chimpanzee (Pan troglodytes troglodytes) lentiviruses, such as SIVcpz[26,27]. Although SIV appears to cause no disease in its natural host [31,35], in spite of an often high level of viral replication, introduction into an unnatural host primate (human or simian) can result in an acquired immunodeficiency syndrome [27,35]. Does HIV-2 protect against infection by HIV-1? Based on cohorts of Senegalese sex workers with a stable prevalence of HIV-2, Travers et al. found an HIV-1 incidence rate of 2.53 among uninfected control subjects, but only an incidence of 1.06 among HIV-2-positive subjects (an approximately 70% rate of protection), even though the incidence rate of gonorrhea (used as a marker of sexual activity and exposure to sexually transmitted diseases) was significantly higher among HIV-2-positive subjects [36]. Additional studies have found protection rates from 52 to 74%, depending on the study design [37,38], and lower HIV-1 viral loads have been seen in HIV-2/HIV-1 dually infected individuals than in patients with only HIV-1 infection [39]. These findings have been questioned, however, by other groups working in other parts of West Africa [37,38,40-43]. Any protective effect of HIV-1 on subsequent HIV-2 infection could not be readily evaluated [36,44]. While controversy continues as to the epidemiological evidence concerning a protective effect of HIV-2 against HIV-1 infection, several possible biological mechanisms for this potential protective effect have been explored. Arya and Gallo found that HIV-2 decreases HIV-1 replication at the molecular level. The inhibition appeared to be caused by a complex pathway [44]. The HIV-2 Tat activation response (TAR) RNA element has also been shown to inhibit HIV-1 transactivation and replication, presumably by competing for HIV-1 Tat or crucial cellular factors, thus inhibiting their interaction with HIV-1 TAR [45,46]. A robust cross-reactive immune response has also been implicated in this inhibition of HIV-1. A majority of HIV-2-positive individuals possess cytotoxic T lymphocyte responses able to recognize HIV-1 gag epitopes, and some individuals can recognize HIV-1 epitopes from multiple clades [47]. In another study, peripheral blood lymphocytes from HIV-2-positive Senegalese prostitutes with high-risk behavior were shown to be 50-fold more resistant than control peripheral blood lymphocyte cultures to HIV-1Bal (a macrophage-tropic, CCR5-using virus) challenge. However, resistance to HIV-1MN was less dramatic (10-fold) and not statistically significant [48]. In a similar study, one-half of HIV-2-infected commercial sex workers in Senegal had peripheral blood mononuclear cells (PBMC) capable of resisting infection by HIV-1JR-CSF (a macrophage-tropic, CCR5-using virus), while the same cells were readily susceptible to infection by HIV-1IIIB, a CXCR4-using virus [49]. In both studies, depletion of CD8-positive T cells or β-chemokines variably reduced the ability to resist HIV-1 viral challenge [48,49]. Broad virus-neutralizing activity in sera has been associated with long-term survival of SIV-infected monkeys, and with decreased maternal-child transmission in HIV-1 [50]. Such neutralizing activity is rare in HIV-1 infection, but is more common in HIV-2 infection [51,52]. The potential protective effect of HIV-2 infection against subsequent HIV-1 challenge requires further study, as the mechanisms underlying such protection could prove valuable in the design of a protective vaccine against HIV-1. Although some encouraging work has been carried out in the area of vaccine development using HIV-2 [53-56], much work remains to be done. Currently, only two candidates for an HIV vaccine are in phase III clinical trials, both based on HIV-1 viral isolates (reviewed in [57], updated information available on www.niaid.nih.gov/daids/vaccine/statuslinks.htm). More investigation into HIV-2-based vaccines, as well as further determination of any HIV-2-mediated protection against subsequent HIV-1 challenge, is called for. Co-receptor use Like HIV-1, HIV-2 has been shown to use CD4 cells as a primary receptor, and several chemokine receptors as co-receptors, for infection of target cells [58]. HIV-1 uses either CCR-5 or CXCR-4 as the major co-receptors for infection [59-62], but can also use other molecules to a lesser extent, such as CCR3 [58]. SIV preferentially uses CCR5 and, occasionally, CXCR4 [63,64]. Surprisingly, considering its lesser pathogenicity, HIV-2 appears to be more flexible in co-receptor usage than is HIV-1. Several HIV-2 strains have been shown to infect certain CD4-negative cell lines, most by using CXCR-4 or CCR-5 alone [65-68], and are better at doing so than is HIV-1. Primary HIV-2 isolates, unlike HIV-1, have also been found to use multiple different co-receptors such as CXCR-4, CXCR5/BLR1, CCR-1, CCR-2b, CCR-3, CCR-4, CCR-5, CCR-8, V28, BOB/GPR15, Bonzo/STRL33, APJ, and US28 for either infection, cell-cell fusion, or both. Unlike HIV-1, most primary HIV-2 isolates tested can productively infect Δ32/Δ32 CCR5 PBMC [64,69,70]. Even though HIV-2 isolates can make use of alternative co-receptors, CCR-5 and CXCR-4 still appear to be the dominant co-receptors used [58,64,69-75]. HIV-2 transcriptional regulation The HIV long terminal repeat contains the promoter and enhancer, in which are found cis-acting elements that respond to T-cell or monocyte activation and play a role in the regulation of viral transcription. HIV-1 isolates in the West (HIV-1B) contain two regulatory elements that bind the transcription factor nuclear factor-κB (NF-κB) and enhance HIV-1 transcription, whereas HIV-1C (prevalent in sub-Saharan Africa and India) contains three NF-κB sites [76]. HIV-2 contains only one such site [77], as does HIV-1E [78]. The expression of cloned NF-κB subunits strongly activates the HIV-1, but not the HIV-2, enhancer [79]. However, HIV-2 contains other elements not found in HIV-1. These include the CD3R/PuB1 and PuB2 sites, which are responsive to stimulation of the CD3 component of the T-cell receptor complex and bind the ets proto-oncogene family member Elf-1, and the pets site, which binds the DEK nuclear protein [77,80-83]. Mutation of any of these elements markedly diminishes the response of the enhancer to cellular activation at the RNA level but does not affect the response to Tat or to other viral transactivating proteins [77,83]. Tumor necrosis factor-α strongly induces the HIV-1 promoter, but only weakly induces that of HIV-2 [79]. Additionally, a site designated peri-κB, identified in the enhancer region of HIV-2 and SIV isolates but not of HIV-1, mediates activation following stimulation of monocytic cell lines but not T-cell lines [84-87]. HIV-Tat, which acts on an RNA response element (TAR) located downstream of the transcriptional start site to enhance transcriptional initiation and, especially, elongation, also differs between HIV-1 and HIV-2. HIV-1 and HIV-2 TAR both respond effectively to HIV-1 Tat, whereas HIV-2 Tat can generally only activate through HIV-2 TAR [4,88]. Whereas HIV-1 TAR RNA contains one stem loop structure, HIV-2 TAR RNA contains two or three (reviewed in [45,88]. HIV-2 TAR can markedly suppress HIV-1 replication, presumably by binding to HIV-1 Tat and/or cellular factors and inhibiting their interaction with HIV-1 TAR [45,46]. Following infection, HIV expression within an individual cell is latent for a variable period of time, until cellular conditions permit replication of the virus [77]. Then cellular events such as immune activation induce viral replication. Since clinical progression is associated with, and accelerated by, an increase in viral replication, differences in the transcriptional activity of HIV-1 and HIV-2 may be, in part, responsible for some of the differences observed in viral load and clinical latency (see later) between these two viruses. HIV-2 proteins Despite the sequence differences noted previously, HIV-2 encodes largely the same gene products as does HIV-1. Like all retroviruses, HIV-1, HIV-2, and SIV encode the gag (nucleocapsid), pol (polymerase-protease), and env (envelope) genes. The env gene varies considerably from isolate to isolate; in HIV-2, it encodes the gp160/140 precursor of the gp120 outer membrane glycoprotein and the gp32-40 transmembrane glycoprotein. In both HIV-1 and HIV-2, gp120 binds the CD4 cell receptor and chemokine co-receptors [7,89]. The gag gene encodes nucleocapsid proteins, and pol encodes the reverse transcriptase, integrase, and protease genes [7,90,91]. The genes gag and pol are well conserved in HIV-1, HIV-2, and SIV, and account for most cross-reactivity seen in enzyme-linked immunosorbent assays for HIV-1 [7]. In addition to gag, pol, and env, HIV-1, HIV-2 and SIV contain five additional reading frames in common, coding for the gene products nef, vif, tat, vpr, and rev. Little is known concerning differences in nef, vif, and rev function between HIV-1 and HIV-2, although many important functions for these proteins have been described in HIV-1 infection (reviewed in [92-100]). While HIV-1 encodes vpu, HIV-2 and SIV encode vpx[6,101,102]. Vpu interferes with surface CD4 expression by binding to CD4 in the endoplasmic reticulum, and targeting it for degradation [93]. The decrease in cell-surface CD4 helps protect cells against re-infection, and allows for release of mature infectious viral particles. The vpu gene product is also required for efficient virus release independent of its CD4 degrading activity [103,104], and has been shown to interfere with the biosynthesis of major histocompatibility complex class I molecules [105]. The vpx and vpr genes are likely to have arisen from a common ancestor, as they are highly similar in sequence [106-108]. The vpx and vpr are 'non-essential' genes that are dispensable for infection and replication in established cell lines in vitro, but are required to various extents for infection of, and replication in, macrophages and PBMC [109,110]. Both are virion associated, and interact with the gag gene product [107,108]. Both are also highly conserved, and vpx is immunogenic in both HIV-2 and SIV [111,112]. Although similar in sequence, HIV-1 vpr and HIV-2 vpr/vpx appear to differ somewhat in their functions in the infected cell. HIV-1 vpr can lead to apoptosis in human cells [106], and vpr from HIV-1, HIV-2, and SIV can all induce cell-cycle (G2) arrest in human and monkey cell lines [101]. Unlike HIV-1 vpr, HIV-2 vpr is poorly represented in viral particles [107,113], although vpx is efficiently incorporated into HIV-2 particles [107]. To infect non-dividing cells, lentiviruses exploit active pathways for nuclear import. HIV-1 vpr and HIV-2 vpx are necessary for efficient nuclear import of the viral pre-integration complex [102,108,113], and as such are required for efficient infection and replication in PBMC and macrophages, although not in T-cell lines or previously activated PBMC [111,113,114]. HIV-2 vpr does not appear to be necessary for infection of macrophages, unlike HIV-1 vpr, possibly because HIV-2 vpx provides the required functions for such infection [114,115]. Deletion of vpx from HIV-2 yields a virus severely attenuated for replication in PBMC. SIV isolates bearing mutations of either vpr or vpx alone could still induce AIDS, although a double mutation rendered the virus apparently non-pathogenic [85,101,116]. Transmission of HIV-2 HIV-2 appears to be transmitted in West Africa mainly by heterosexual contact or by contact with infected blood [16,20]. HIV-2 transmission appears to differ from that of HIV-1 in two ways. First, HIV-2 is less readily transmitted by sexual contact than is HIV-1 [8]. Efficiency of heterosexual transmission of HIV-2 is estimated to be five times lower than that of HIV-1 [117]. Prevalence rates of HIV-2 infection increase with increasing age in both men and women, suggesting a lower transmission rate than for HIV-1, with repeated exposures necessary [20,23,118-120]. Additionally, the rate of viral shedding in cervical samples was shown to be 16% in HIV-2-positive women, compared with 36.4% in HIV-1-positive women, possibly explaining some of the difference in rates of heterosexual transmission [121]. Second, transmission from infected mothers to children during pregnancy or through breast milk is much less likely with HIV-2 than with HIV-1 [8,118,122]. Although vertical transmission occurs in approximately one-third of untreated HIV-1-positive pregnancies [123], most studies have shown that vertical transmission of HIV-2 occurs rarely (about 0-4% of all HIV-2-positive pregnancies) [122-126]. In one study, 11 mothers infected with both HIV-1 and HIV-2 transmitted HIV-1 to their offspring, but in only one case was HIV-2 transmitted (in this case, along with HIV-1) [118]. Clinical course: why is HIV-2 less pathogenic than HIV-1? HIV-2 causes AIDS [3,20,127-130], but the period between infection and development of AIDS appears to be substantially longer than that for HIV-1 [9,131]. This difference in disease progression could, in part, be due to lower viral loads in those infected with HIV-2 than in those infected with HIV-1 [19,39,132-134]. However, once disease develops, patients with HIV-2 generally have most of the same signs and symptoms as do HIV-1 patients. For HIV-1 infection, the main determinant of future clinical progression to AIDS appears to be the level of plasma viremia, as measured by HIV-RNA [135-137]. HIV-1 long-term non-progressors, who have normal and stable CD4 cell counts for at least 12-16 years post-infection, tend to have plasma levels of RNA orders of magnitude lower than more rapid progressors [136,138]. While the majority of HIV-2-infected individuals live much longer than do HIV-1-infected people, this dichotomy between rapid and slow progression to AIDS may hold true in HIV-2 infection as well. In Guinea-Bissau, the mortality rate for adults younger than 45 years of age infected with HIV-2 versus uninfected individuals was 5 : 1, whereas for older people mortality was much closer to 1 : 1. Mortality did not increase with age and, in most cases, infection with HIV-2 did not affect survival [139,140], suggesting the existence of two populations: one that progresses quickly and dies of AIDS, and the remainder who become long-term non-progressors. A similar dichotomy was correlated with viral genotype in a study by Grassly et al., although no correlation was found between viral genotype and high proviral load or low CD4 cell counts [141]. Differences in transmission and clinical course between HIV-2 and HIV-1 may be explained, at least in part, by differences in viral load. Advanced disease and higher viral loads have been correlated with increased vertical transmission of HIV-2 [122]. HIV-2 infection leads to much lower levels of plasma viremia at all stages of disease and levels of circulating CD4-positive T cells, with a viral load generally 30 times lower than that of HIV-1 [19,39,133,134]. The viral load 'set point' following initial infection is markedly lower in HIV-2-positive patients as compared with HIV-1-positive patients [39]. Increasing viral loads are correlated with decreasing CD4 cell counts in both HIV-1 and HIV-2 infection [19,133-135]. Decreasing CD4 cell counts are further correlated with disease progression in both HIV-1 and HIV-2 infection [19,130,135]. Interestingly, proviral load (viral DNA integrated into target cells) appears to be similar between HIV-1 and HIV-2, even when adjusted for clinical status [132,142-144]. In HIV-2, proviral load is usually found inversely correlated with CD4 cell counts [132,144] and directly associated with disease [143]. However, levels of proviral DNA and plasma viral RNA were not correlated in subjects [132,133]. Thus, while HIV-1 and HIV-2 infection lead to similar levels of latently or non-productively infected target cells, viral replication, and thus plasma viremia, is very much lower in HIV-2 than in HIV-1. This suggests that increases in viremia may be due, at least in part, to changes in RNA expression from the DNA templates (transcription), rather than to an increase in the total number of templates available. Differences in HIV-2 and HIV-1 transcriptional regulation (see earlier) could thus account for some of the contrast in viral load between HIV-1 and HIV-2. Additionally, HIV-2 infection may lead to a higher proportion of defective viral genomes unable to replicate. As viral load has a great impact on clinical outcome for HIV-infected people, these differences between HIV-1 and HIV-2 appear to be important. While differences in viral load and disease progression following HIV-2, as compared with HIV-1, infection may be due at least in part to viral transcription and replication rates, other factors are probably also at work. Differences in the ability of HIV-2 and HIV-1 to kill cells and to evoke an effective immune response have been reported (reviewed in [145]). At least two groups have reported lower rates of T-cell apoptosis associated with HIV-2 infection than with HIV-1 infection [145-147]. As has been very recently reviewed in depth elsewhere [145], studies have shown that HIV-2 evokes a vigorous humoral and cellular immune response, with what appears to be a broader neutralizing antibody response and more efficient cell-mediated immunity than is seen with HIV-1. Thus, the lesser pathogenicity of HIV-2 may be due to a lower rate of viral replication and/or a heightened immune response, either or both of which could lead to a lower viral load, and/or to the lesser degree of apoptosis apparently induced by HIV-2. Clinical manifestations of HIV-2 infection Although HIV-2 disease may progress more slowly to AIDS, AIDS in HIV-2-infected people presents with a similar spectrum of signs and symptoms as in HIV-1-infected individuals, both in adults and children [128-130,148,149]. Presenting symptoms of HIV-2 infection include generalized lymphadenopathy [150,151], candidiasis, pulmonary disease [128], generalized pruritic dermatitis, weight loss of greater than 10% body weight, and diarrhea or fever for greater than 1 month [130,150]. Those infected with HIV-2 sometimes complain of fever, diarrhea, and/or oral candidiasis around the time of conversion [130]. Major symptoms of HIV-2 infection (as with HIV-1 infection in similar areas) tend to be wasting (cachexia), chronic diarrhea, candidiasis, cryptosporidiosis, cryptococcal meningitis, and recurrent bacterial infection [148,150]. The major causes of death among HIV-2 AIDS patients are bacteremia/septicemia, cerebral toxoplasmosis [152], cachexia, meningoencephalitis, and pulmonary infiltrates of undiagnosed etiology [128]. Although similar in clinical manifestations to HIV-1, HIV-2 disease does show some differences: HIV-2 does not appear to be associated with increasing rates of clinical tuberculosis [150], or is at least far less so than is HIV-1 [153]. Severe multi-organ cytomegalovirus infection, HIV encephalitis, and cholangitis were all found to be more severe in HIV-2-related AIDS than in that associated with HIV-1. As these three pathologies are generally associated with severe immunosuppression in late-stage HIV-1 disease [154], this suggests that HIV-2-infected patients may live longer in the terminal stages of infection [152]. As with HIV-1-related AIDS, CD4 cell and total lymphocyte counts are decreased as compared with controls, as is the CD4/CD8 cell ratio [9,118,130,151]. However, these decreases are not normally as severe as in HIV-1 disease [130,155]. In addition, HIV-2 infection leads to decreases in lymphocyte proliferation assays (a measure of total cell-mediated immunity) to candida, purified protein derivative, and phytohemagglutinin, which are similar to, but less dramatic than, the changes seen with HIV-1 infection [9,119,151]. HIV-2-positive subjects tend to be older than HIV-1-positive subjects [128,153,155], although whether this is due to HIV-2-positive people living longer than HIV-1-positive people, a cohort effect, a necessity for more cumulative exposures to HIV-2 before seroconversion, or a combination of these factors is unclear. Kaposi's sarcoma (KS), a vascular malignancy common in AIDS patients in the United States prior to the widespread use of highly active antiretroviral therapies, is an endemic disease in Eastern and Central Africa. KS is associated with infection by the human herpes virus 8 (also called KS-associated herpes virus) [156-158]. Infection with HIV-1 increases the risk for developing KS lesions 20 000-fold [159]. However, an association between KS and HIV-2 has not been demonstrated. In western Africa, no obvious increase in the incidence of KS has been noted, despite a high incidence of HIV-2 infection [139]. Even among HIV-2 AIDS patients, few cases of KS have been observed [3,139,150]. For HIV-1 versus HIV-2 infection, the odds ratio for developing KS has been calculated to be 16, despite similar incidences of KS-associated herpes virus in the two populations [139]. Some groups have postulated that the HIV-1 viral transactivating protein Tat is an angiogenic factor, due to an RGD (arginine, glycine, aspartate) domain within the protein, which HIV-2 Tat lacks [139,160] (see www.ncbi.nlm.nih.gov). Counseling and treatment HIV-2 is sensitive to nucleoside reverse transcriptase inhibitors (NRTI) in vitro and in vivo, but may be less so than is HIV-1 [161-164]. Also, the use of a nucleotide analog reverse transcriptase (RT) inhibitor (in this case, Tenofovir) has been demonstrated to serve as effective post-exposure prophylaxis if given within 36 h of intravaginal exposure to HIV-2 in a pig-tailed macaque model [165]. HIV-2 is not sensitive to non-nucleoside reverse transcriptase inhibitors (NNRTI) [161,166], perhaps due to mutations found within the NNRTI binding pocket of the RT protein. In one study, 12 primary HIV-2 isolates contained at least one mutation associated with NNRTI resistance in HIV-1, and most had two [163]. In contrast, HIV-2 does generally appear to be sensitive to protease inhibitors in vitro[167]. Determination of the exact in vivo activity of these drugs is more difficult with HIV-2 than with HIV-1 because there is no Food and Drug Administration approved assay to determine HIV-2 plasma viral load [161], lower baseline levels of plasma viremia are often found in HIV-2 patients as compared with those with HIV-1 (often too low to measure) [19,133,134,162], and because most HIV-2-infected people live in West Africa, where access to drugs is limited [162,163]. One study addressing the treatment of an HIV-2-infected patient with NRTI and protease inhibitor combination therapy showed both an increase in CD4 cells and a decrease in HIV-2 proviral copies in PBMC over the course of treatment [162]. However, as is the case with HIV-1, resistance to both RT and protease inhibitors can arise while on therapy for HIV-2 [163]. More studies looking at drug efficacy in vivo are necessary to determine optimal treatment strategies for HIV-2-infected patients. Treatment of opportunistic infections (OI) in HIV-2-infected patients appears to be similar, although perhaps more effective, than in those with HIV-1 infection [9,127,168], although very little data about treatment of OI specifically in HIV-2 patients exist. As CD4 cell counts in HIV-2 disease appear to reflect the state of immunosuppression [130,155], it seems reasonable to base prophylaxis on CD4 cell counts, just as is done for HIV-1. However, people with HIV-2 infection may require a less aggressive regimen for prophylaxis and/or long-term treatment than do people with HIV-1. Studies need to address these issues, however, before exact strategies can be proposed. Due to the differences in the clinical course of HIV-2 compared with HIV-1, it seems likely that a more optimistic tenor can be adopted when counseling HIV-2-infected patients, although any discussions of treatment options must address our current lack of concrete clinical experience with antiretroviral therapies and OI in patients with HIV-2. As with HIV-1-infected persons, these patients must be cautioned to inform any prospective sexual partner of their status, use barrier protections such as condoms or dental dams when having sexual contact, and not to donate blood or participate in any activity that would expose others to their blood (e.g., sharing of needles or razors). In view of the low rate of vertical transmission, and the lower mortality rate, pregnancy in the HIV-2-infected woman presents a much lower risk to the baby in terms of infection, and also poses a lower risk for maternal death (leaving the child an orphan) than does pregnancy in the HIV-1-infected woman. Based on the data with HIV-1, demonstrating a two-thirds drop in infection rates with antiretroviral therapy of mother and baby [169], we would recommend similar treatment of HIV-2-infected mothers and their babies. Current recommendations for the prevention of perinatal treatment include adding zidovudine to the patient's current drug regimen, and treating the baby with zidovudine also [170-173]. Although some NNRTI are being evaluated for use in pregnancy [171], due to the resistance demonstrated by HIV-2 to NNRTI, we would caution against use of such NNRTI in HIV-2-infected pregnant women. Conclusions Although less prevalent than HIV-1, HIV-2 remains an important pathogen in western Africa, as well as in Portugal and some countries formerly colonized by the Portuguese. Although similar to HIV-1, HIV-2 also has distinct biological differences. For example, although HIV-2-associated AIDS is clinically similar to that caused by HIV-1, significant differences exist between HIV-2 and HIV-1 in regards to disease latency (longer with HIV-2) and transmission rate (lower with HIV-2), as well as in viral transcriptional regulation and receptor usage. Antiretroviral treatment for HIV-2 has not been well studied. Based on laboratory studies and very limited clinical experience, and by extrapolating from HIV-1 clinical studies, it appears that patients with HIV-2 infection and low CD4 cell counts would benefit from treatment with NRTI and protease inhibitors, but not NNRTI therapy. Treatment of opportunistic infections in HIV-2 disease, although not well characterized, should probably be approached in a similar manner to that in HIV-1 disease. Prophylaxis for opportunistic infections may prove to be less necessary with HIV-2 than HIV-1 infection, but it seems reasonable to base any regimen on CD4 cell counts. Furthermore, studies investigating the differences in HIV-2 and HIV-1 infection, replication, and transmission remain of vital importance, as the information obtained could significantly impact on strategies for treatment and development of vaccines against both HIV-2 and HIV-1 infection. Acknowledgments The authors would like to thank Francis Probst, Nersi Nikakhtar, Monty Montano, and Phyllis Kanki for their helpful comments on the manuscript." @default.
W2068171898 created "2016-06-24" @default.
W2068171898 creator A5075367506 @default.
W2068171898 creator A5078298496 @default.
W2068171898 date "2001-01-01" @default.
W2068171898 modified "2023-10-11" @default.
W2068171898 title "Infection with HIV-2" @default.
W2068171898 cites W1489477411 @default.
W2068171898 cites W1499808375 @default.
W2068171898 cites W1512008015 @default.
W2068171898 cites W1523087205 @default.
W2068171898 cites W1523507291 @default.
W2068171898 cites W1542751540 @default.
W2068171898 cites W1567120555 @default.
W2068171898 cites W1567318029 @default.
W2068171898 cites W1571744798 @default.
W2068171898 cites W1576999979 @default.
W2068171898 cites W1635094878 @default.
W2068171898 cites W1642524132 @default.
W2068171898 cites W168408284 @default.
W2068171898 cites W1741697594 @default.
W2068171898 cites W1753280777 @default.
W2068171898 cites W1830856266 @default.
W2068171898 cites W1837528589 @default.
W2068171898 cites W1865130151 @default.
W2068171898 cites W1909395851 @default.
W2068171898 cites W1945723923 @default.
W2068171898 cites W1948862973 @default.
W2068171898 cites W1952459954 @default.
W2068171898 cites W1969538535 @default.
W2068171898 cites W1970386774 @default.
W2068171898 cites W1970633905 @default.
W2068171898 cites W1972276296 @default.
W2068171898 cites W1973684423 @default.
W2068171898 cites W1974282283 @default.
W2068171898 cites W1975768130 @default.
W2068171898 cites W1976329458 @default.
W2068171898 cites W1976581012 @default.
W2068171898 cites W1981440980 @default.
W2068171898 cites W1981644527 @default.
W2068171898 cites W1985777277 @default.
W2068171898 cites W1986266125 @default.
W2068171898 cites W1989035987 @default.
W2068171898 cites W1992116917 @default.
W2068171898 cites W1992145903 @default.
W2068171898 cites W1992807773 @default.
W2068171898 cites W1994922093 @default.
W2068171898 cites W1995303015 @default.
W2068171898 cites W1996183144 @default.
W2068171898 cites W1998102826 @default.
W2068171898 cites W1999139312 @default.
W2068171898 cites W2000362582 @default.
W2068171898 cites W2000551837 @default.
W2068171898 cites W2002465178 @default.
W2068171898 cites W2003868334 @default.
W2068171898 cites W2004691650 @default.
W2068171898 cites W2005149743 @default.
W2068171898 cites W2006409246 @default.
W2068171898 cites W2006958762 @default.
W2068171898 cites W2010840723 @default.
W2068171898 cites W2011389067 @default.
W2068171898 cites W2012139740 @default.
W2068171898 cites W2014531222 @default.
W2068171898 cites W2020096299 @default.
W2068171898 cites W2021077736 @default.
W2068171898 cites W2021906926 @default.
W2068171898 cites W2022261032 @default.
W2068171898 cites W2027384017 @default.
W2068171898 cites W2028013252 @default.
W2068171898 cites W2032438721 @default.
W2068171898 cites W2033078023 @default.
W2068171898 cites W2033256737 @default.
W2068171898 cites W2034858284 @default.
W2068171898 cites W2037442795 @default.
W2068171898 cites W2039975091 @default.
W2068171898 cites W2042884300 @default.
W2068171898 cites W2043592421 @default.
W2068171898 cites W2044385030 @default.
W2068171898 cites W2044416560 @default.
W2068171898 cites W2044816496 @default.
W2068171898 cites W2045186821 @default.
W2068171898 cites W2050223395 @default.
W2068171898 cites W2050489828 @default.
W2068171898 cites W2050598058 @default.
W2068171898 cites W2053395531 @default.
W2068171898 cites W2053711547 @default.
W2068171898 cites W2056360005 @default.
W2068171898 cites W2056930919 @default.
W2068171898 cites W2059888261 @default.
W2068171898 cites W2059910556 @default.
W2068171898 cites W2060371587 @default.
W2068171898 cites W2062532841 @default.
W2068171898 cites W2063286219 @default.
W2068171898 cites W2069560072 @default.
W2068171898 cites W2072325806 @default.
W2068171898 cites W2073423278 @default.
W2068171898 cites W2074171860 @default.
W2068171898 cites W2075416959 @default.