Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana.

An obesity paradox has been proposed in many conditions including HIV. Studies conducted to investigate obesity and its effect on HIV disease progression have been inconclusive and are lacking for African settings. This study investigated the relationship between overweight/obesity (BMI≥25 kg/m2) and HIV disease progression in HIV+ asymptomatic adults not on antiretroviral treatment (ART) in Botswana over 18 months. A cohort study in asymptomatic, ART-naïve, HIV+ adults included 217 participants, 139 with BMI of 18·0-24·9 kg/m2 and seventy-eight participants with BMI≥25 kg/m2. The primary outcome was time to event (≥25 % decrease in cluster of differentiation 4 (CD4) cell count) during 18 months of follow-up; secondary outcomes were time to event of CD4 cell count<250 cells/µl and AIDS-defining conditions. Proportional survival hazard models were used to compare hazard ratios (HR) on time to events of HIV disease progression over 18 months. Higher baseline BMI was associated with significantly lower risk of an AIDS-defining condition during the follow-up (HR 0·218; 95 % CI 0·068, 0·701; P=0·011). Higher fat mass at baseline was also significantly associated with decreased risk of AIDS-defining conditions during the follow-up (HR 0·855; 95 % CI 0·741, 0·987; P=0·033) and the combined outcome of having CD4 cell count≤250/µl and AIDS-defining conditions, whichever occurred earlier (HR 0·918; 95 % CI 0·847, 0·994; P=0·036). All models were adjusted for covariates. Higher BMI and fat mass among the HIV-infected, ART-naïve participants were associated with slower disease progression. Mechanistic research is needed to evaluate the association between BMI, fat mass and HIV disease progression.

Tuberculosis in human immunodeficiency virus-infected children starting antiretroviral therapy in Côte d'Ivoire.

SETTING: In Côte d'Ivoire, more than 2000 human immunodeficiency virus (HIV) infected children aged <15 years were started on antiretroviral therapy (ART) during 2004-2008. OBJECTIVES: To estimate tuberculosis (TB) incidence and determinants among ART enrollees. DESIGN: A nationally representative retrospective cohort study among 2110 children starting ART during 2004-2008 at 29 facilities. RESULTS: At ART initiation, the median age was 5.1 years; 82% had World Health Organization Stage III/IV, median CD4% was 11%, 42% were severely undernourished (weight-for-age Z-score [WAZ] <-3), and 150 (7%) were taking anti-tuberculosis treatment. Documentation of TB screening before ART declined from 63% to 46% during 2004-2008. Children taking anti-tuberculosis treatment at ART enrollment had a lower median CD4% (9.0% vs. 11.0%, P = 0.037) and a higher prevalence of WAZ <-3 (59% vs. 40%, P < 0.001). Among children considered TB-free at ART enrollment, TB incidence was 6.28/100 child-years during days 0-90 of ART, declining to 0.56/100 child-years after 180 days. Children with one unit higher WAZ at ART enrollment had 13% lower TB incidence (adjusted HR 0.87, 95%CI 0.77-1.00, P= 0.047). CONCLUSIONS: Ensuring clinician compliance with TB screening before ART and ensuring earlier ART initiation before children suffer from advanced HIV disease and nutritional compromise might reduce TB morbidity during ART.

Effects of HIV-related stigma among an early sample of patients receiving antiretroviral therapy in Botswana.

Botswana, with its estimated HIV prevalence of 37%, instituted a policy of universal access to antiretroviral therapy (ART) in 2002. Initial enrolment lagged behind expectations, with a shortfall in voluntary testing that observers have attributed to HIV-related stigma - although there are no published data on stigma among HIV-positive individuals in Botswana. We interviewed 112 patients receiving ART in 2000, finding evidence of pervasive stigma in patterns of disclosure, social sequelae, and delays in HIV testing. Ninety-four percent of patients reported keeping their HIV status secret from their community, while 69% withheld this information even from their family. Twenty-seven percent of patients said that they feared loss of employment as a result of their HIV status. Forty percent of patients reported that they delayed getting tested for HIV; of these, 51% cited fear of a positive test result as the primary reason for delay in seeking treatment, which was often due to HIV-related stigma. These findings suggest that success of large-scale national ART programmes will require initiatives targeting stigma and its social, economic and political correlates.

Association between virus-specific T-cell responses and plasma viral load in human immunodeficiency virus type 1 subtype C infection.

Virus-specific T-cell immune responses are important in restraint of human immunodeficiency virus type 1 (HIV-1) replication and control of disease. Plasma viral load is a key determinant of disease progression and infectiousness in HIV infection. Although HIV-1 subtype C (HIV-1C) is the predominant virus in the AIDS epidemic worldwide, the relationship between HIV-1C-specific T-cell immune responses and plasma viral load has not been elucidated. In the present study we address (i) the association between the level of plasma viral load and virus-specific immune responses to different HIV-1C proteins and their subregions and (ii) the specifics of correlation between plasma viral load and T-cell responses within the major histocompatibility complex (MHC) class I HLA supertypes. Virus-specific immune responses in the natural course of HIV-1C infection were analyzed in the gamma interferon (IFN-gamma)-enzyme-linked immunospot assay by using synthetic overlapping peptides corresponding to the HIV-1C consensus sequence. For Gag p24, a correlation was seen between better T-cell responses and lower plasma viral load. For Nef, an opposite trend was observed where a higher T-cell response was more likely to be associated with a higher viral load. At the level of the HLA supertypes, a lower viral load was associated with higher T-cell responses to Gag p24 within the HLA A2, A24, B27, and B58 supertypes, in contrast to the absence of such a correlation within the HLA B44 supertype. The present study demonstrated differential correlations (or trends to correlation) in various HIV-1C proteins, suggesting (i) an important role of the HIV-1C Gag p24-specific immune responses in control of viremia and (ii) more rapid viral escape from immune responses to Nef with no restraint of plasma viral load. Correlations between the level of IFN-gamma-secreting T cells and viral load within the MHC class I HLA supertypes should be considered in HIV vaccine design and efficacy trials.

Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C.

A systematic analysis of immune responses on a population level is critical for a human immunodeficiency virus type 1 (HIV-1) vaccine design. Our studies in Botswana on (i) molecular analysis of the HIV-1 subtype C (HIV-1C) epidemic, (ii) frequencies of major histocompatibility complex class I HLA types, and (iii) cytotoxic T-lymphocyte (CTL) responses in the course of natural infection allowed us to address HIV-1C-specific immune responses on a population level. We analyzed the magnitude and frequency of the gamma interferon ELISPOT-based CTL responses and translated them into normalized cumulative CTL responses. The introduction of population-based cumulative CTL responses reflected both (i) essentials of the predominant virus circulating locally in Botswana and (ii) specificities of the genetic background of the Botswana population, and it allowed the identification of immunodominant regions across the entire HIV-1C. The most robust and vigorous immune responses were found within the HIV-1C proteins Gag p24, Vpr, Tat, and Nef. In addition, moderately strong responses were scattered across Gag p24, Pol reverse transcriptase and integrase, Vif, Tat, Env gp120 and gp41, and Nef. Assuming that at least some of the immune responses are protective, these identified immunodominant regions could be utilized in designing an HIV vaccine candidate for the population of southern Africa. Targeting multiple immunodominant regions should improve the overall vaccine immunogenicity in the local population and minimize viral escape from immune recognition. Furthermore, the analysis of HIV-1C-specific immune responses on a population level represents a comprehensive systematic approach in HIV vaccine design and should be considered for other HIV-1 subtypes and/or different geographic areas.

Human immunodeficiency virus type 1 subtype C molecular phylogeny: consensus sequence for an AIDS vaccine design?

An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C) in the AIDS epidemic has been associated with a high prevalence of HIV-1C infection in the southern African countries and with an expanding epidemic in India and China. Understanding the molecular phylogeny and genetic diversity of HIV-1C viruses may be important for the design and evaluation of an HIV vaccine for ultimate use in the developing world. In this study we analyzed the phylogenetic relationships (i) between 73 non-recombinant HIV-1C near-full-length genome sequences, including 51 isolates from Botswana; (ii) between HIV-1C consensus sequences that represent different geographic subsets; and (iii) between specific isolates and consensus sequences. Based on the phylogenetic analyses of 73 near-full-length genomes, 16 "lineages" (a term that is used hereafter for discussion purposes and does not imply taxonomic standing) were identified within HIV-1C. The lineages were supported by high bootstrap values in maximum-parsimony and neighbor-joining analyses and were confirmed by the maximum-likelihood method. The nucleotide diversity between the 73 HIV-1C isolates (mean value of 8.93%; range, 2.9 to 11.7%) was significantly higher than the diversity of the samples to the consensus sequence (mean value of 4.86%; range, 3.3 to 7.2%, P < 0.0001). The translated amino acid distances to the consensus sequence were significantly lower than distances between samples within all HIV-1C proteins. The consensus sequences of HIV-1C proteins accompanied by amino acid frequencies were presented (that of Gag is presented in this work; those of Pol, Vif, Vpr, Tat, Rev, Vpu, Env, and Nef are presented elsewhere [http://www.aids.harvard.edu/lab_research/concensus_sequence.htm]). Additionally, in the promoter region three NF-kappa B sites (GGGRNNYYCC) were identified within the consensus sequences of the entire set or any subset of HIV-1C isolates. This study suggests that the consensus sequence approach could overcome the high genetic diversity of HIV-1C and facilitate an AIDS vaccine design, particularly if the assumption that an HIV-1C antigen with a more extensive match to the circulating viruses is likely to be more efficacious is proven in efficacy trials.

Identification of human immunodeficiency virus type 1 subtype C Gag-, Tat-, Rev-, and Nef-specific elispot-based cytotoxic T-lymphocyte responses for AIDS vaccine design.

The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In this study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses in the southern African country of Botswana. CTLs were shown to be an important component of the immune response to control HIV-1 infection. The definition of optimal and dominant epitopes across the HIV-1C genome that are targeted by CTL is critical for vaccine design. The characteristics of the predominant virus that causes the HIV-1 epidemic in a certain geographic area and also the genetic background of the population, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccinee and in the general population. The enzyme-linked immunospot (Elispot) gamma interferon assay has recently been shown to be a reliable tool to map optimal CTL epitopes, correlating well with other methods, such as intracellular staining, tetramer staining, and the classical chromium release assay. Using Elispot with overlapping synthetic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C-specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative Elispot-based CTL responses combined with diversity and sequence consensus data provide an additional characterization of immunodominant regions across the HIV-1C genome. Results of the study suggest that the construction of a poly-epitope subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant CTL epitopes across the viral genome, derived from predominant HIV-1 viruses, might be a logical approach to the design of a vaccine against AIDS.

Identification of most frequent HLA class I antigen specificities in Botswana: relevance for HIV vaccine design.

Since the mid-1990s, southern African countries have been experiencing an expansion of human immunodeficiency virus type 1 (HIV-1) infection caused by HIV-1 subtype C. To facilitate the design of an HLA-based HIV vaccine, we studied the distribution of the HLA class I antigen specificities in Botswana, a southern African country with a high prevalence of HIV infection. Botswana's highly efficient health care system and its central geographical location within southern Africa suggests that it might be an appropriate candidate site for future trials of an HLA-based HIV vaccine. Specificities of HLA class I genes have been investigated in DNA samples obtained from 161 persons of Botswana origin by polymerase chain reaction (PCR) with sequence-specific primers. We identified 4 HLA-A, 7 HLA-B, and 5 HLA-C specificities that were observed at high frequencies in the Botswana population: A30, A02, A23, A68, B58, B72, B42, B8, B18, B44, B45, Cw7, Cw2, Cw17, Cw6, and Cw4. HLA-A30, A02, A23, A68, B58, Cw2, Cw4, Cw6, Cw7, and Cw17 were observed at frequencies of more than 10%. The frequency of HLA-A30 was 27.3%. HLA-B58 (17.9%) was the most frequent generic HLA-B type. Other frequent antigen specificities detected for the HLA-B were B72 (9.6%), B42 (9.3%), B8 (7.4%), B18 (7.4%), B44 (7.4%), and B45 (6.4%). Analysis of haplotype frequencies revealed that haplotypes HLA-A30/HLA-B58 (6.7%), A30/B42 (6.1%), A30/B8 (4.1%), A30/B45 (3.2%), and A23/B58 (2.5%) were the most frequent among two-locus haplotypes. The comparison of HIV-positive patients and noninfected controls for HLA class I specificities confirmed the previously described association of A2/A6802 supertype with resistance to HIV. Our study suggested an increased resistance to HIV infection associated with A68 rather than A2. We also found that the generic HLA-B58 type was associated with increased susceptibility to HIV infection. Our findings suggest that the design of an HLA-based HIV vaccine that includes multiple CTL epitopes restricted by identified common HLA class I specificities might target up to 97.5% of the population in Botswana. The results of this study extend the HLA map to a southern African country that has high rates of HIV and also provide a database for the design of an HLA-based HIV vaccine.

Clinical care issues for women living with HIV and AIDS in the United States.

As the number of women infected with HIV in the United States continues to increase, the medical community is faced with the challenge of providing adequate and appropriate care to them. This paper reviews key questions concerning the state of knowledge on the epidemiology, biology, and clinical care of women living with HIV and AIDS in the United States. Because heterosexual transmission accounts for a growing number of cases among women, biological factors and cofactors that may enhance women's susceptibility to HIV infection are also reviewed. HIV-related gynecological issues are presented separately to evaluate whether gynecological complications are distinct in HIV-uninfected and HIV-infected women. Questions of whether there are sex-specific differences in the efficacy and adverse effects of new antiviral agents are discussed. In addition, significant gaps are highlighted that still exist in our understanding of both the effects of HIV and HIV-related drugs upon pregnancy. Finally, the psychiatric stresses and complications that affect women living with HIV and AIDS are also discussed. In each section of this review, gaps in our knowledge of these issues are identified. To properly address these disparities in knowledge, not only do efforts to gather sex-specific biomedical data need to be more exacting, but there is a distinct need to conduct more sex-specific research concerning HIV.

HIV type 1 A/J recombinant with a pronounced pol gene mosaicism.

A nearly full-length genome sequence of a novel HIV-1 A/J recombinant with a complex structure of the pol gene has been analyzed. This virus was isolated in 1998 from a 35-year-old female from Botswana. The virus demonstrated a dual pattern for CXCR4/CCR5 coreceptor utilization. Using short-term enrichment of the donor's PBMCs, the 98BW21 isolate was long-range amplified, cloned, and sequenced. The sequence of the clone 98BW21.17 spanned 9103 bp from the PBS site to the U5 region of the 3' LTR. The phylogenetic relationship of the 98BW21.17 clone to HIV-1 sequences represented by M, N, and O groups and A-K subtypes of the M group was examined across the entire viral genome. The 98BW21.17 clone demonstrated a unique phylogenetic topology clustering within subtype A or subtype J reference sequences. However, the subtype origin of two regions within the pol gene (p51 RT and integrase) could not be identified. Recombination patterns of the 98BW21.17 clone were different from known AGJ/AGIJ-type viruses such as isolates BFP90 and 95ML84. This study demonstrated the existence and replication competence of a new dual-tropic X4/R5 recombinant form of HIV-1 on the subtype J backbone. The nucleotide sequence of the 98BW21.17 clone was submitted to GenBank under accession number AF192135.

Molecular cloning and phylogenetic analysis of human immunodeficiency virus type 1 subtype C: a set of 23 full-length clones from Botswana.

To better understand the virological aspect of the expanding AIDS epidemic in southern Africa, a set of 23 near-full-length clones of human immunodeficiency virus type 1 (HIV-1) representing eight AIDS patients from Botswana were sequenced and analyzed phylogenetically. All study viruses from Botswana belonged to HIV-1 subtype C. The interpatient diversity of the clones from Botswana was higher than among full-length isolates of subtype B or among a set of full-length HIV-1 genomes of subtype C from India (mean value of 9. 1% versus 6.5 and 4.3%, respectively; P < 0.0001 for both comparisons). Similar results were observed in all genes across the entire viral genome. We suggest that the high level of HIV-1 diversity might be a typical feature of the subtype C epidemic in southern Africa. The reason or reasons for this diversity are unclear, but may include an altered replication efficiency of HIV-1 subtype C and/or the multiple introduction of different subtype C viruses.

Relation between HIV-2 proviral load and CD4+ lymphocyte count differs in monotypic and dual HIV infections.

OBJECTIVE: To explore and compare the relations between proviral DNA load and CD4+ lymphocyte counts in both HIV-2 monotypic and HIV dual infection. STUDY DESIGN/METHODS: In Dakar, Senegal, where the HIV-1 and HIV-2 epidemics overlap, serum and peripheral blood mononuclear cell (PBMC) DNA samples were collected from registered female sex workers and hospitalized patients. Sera were evaluated for reactivity to antigens of HIV-1 and HIV-2 by immunoblot; dual reactivity was confirmed with recombinant envelope peptides for HIV-1 and HIV-2. These samples were then subjected to HIV-1 and HIV-2 proviral DNA polymerase chain reaction (PCR). To evaluate the HIV-2 cellular proviral DNA loads, a quantitative competitive PCR (QC-PCR) was developed using nested primers to amplify the gag region of HIV-2. This assay used an internal competitor generated by inserting 25 bp in the first-round PCR target sequence. T-lymphocyte subset counts were estimated by flow cytometry for both HIV-2 monotypic and dually infected persons. RESULTS: 35 HIV-2-infected and 33 dually seroreactive samples were evaluated in this study. The CD4+ lymphocyte counts were similar in both groups, with mean values of 449 +/- 390 cells/mm3 for the HIV-2 monotypic infected persons and 476 +/- 308 cells/mm3 among the dually infected persons. However, the median proviral loads differed significantly, with those in the HIV-2 group ranging from 63.2 to 669.8 copies/10(5) CD4+ cells and demonstrating an inverse correlation with CD4+ lymphocyte count. The HIV dually infected persons showed less variation in viral load, ranging from 9.9 to 43.3 copies/10(5) CD4+ cells. Among the HIV dually infected persons, low HIV-2 proviral load was correlated with low CD4+ lymphocyte counts. CONCLUSIONS: The HIV-2 proviral loads in HIV dually infected persons were significantly lower than those in HIV-2 monotypically infected individuals (P < .0001), despite comparable CD4+ lymphocyte counts. These results suggest that different HIV-2 proviral dynamics prevail in HIV dual infection.

Human immunodeficiency virus type 1 subtypes differ in disease progression.

At least 10 different genetic human immunodeficiency virus type 1 (HIV-1) subtypes (A-J) are responsible for the AIDS pandemic. Much of the understanding of HIV-1 disease progression derives from studies in the developed world where HIV infection is almost exclusively subtype B. This has led many to question whether the properties and consequences of HIV-1 infection can be generalized across subtypes that afflict the majority of infected persons in the developing world. From 1985 to 1997, a prospective study of registered female sex workers in Senegal tracked the introduction and spread of HIV-1 subtypes A, C, D, and G. In clinical follow-up, the AIDS-free survival curves differed by HIV-1 subtype. Women infected with a non-A subtype were 8 times more likely to develop AIDS than were those infected with subtype A (hazard ratio=8.23; P=. 009), the predominant subtype in the study. These data suggest that HIV-1 subtypes may differ in rates of progression to AIDS.

Antibodies to the HIV type 2 core protein p26 and Vpx: association with disease progression.

A longitudinal cohort study was conducted to define the prevalence and temporal pattern of antibody response to the HIV-2 virion-associated proteins p26gag and Vpx. One hundred and forty-one asymptomatic HIV-2-infected women were enrolled, and followed for up to 11 years. Eighty-one percent of the subjects had antibodies to p26, and 51% to Vpx; response to these two antigens was not correlated. The response to both proteins was determined early in infection, and remained stable over time. The absence of antibodies to p26 was a highly significant predictor of CDC category IV HIV-related disease (p < 0.01) in both univariate and multivariate analysis. Antibody response to Vpx alone was not associated with disease progression. However, those individuals lacking anti-p26 antibodies, and with anti-Vpx antibodies, were six times more likely to be classified as CDC category IV by the end of the study (p < 0.01). This represents the first identification of virus-specific serological markers for HIV-2-related disease progression.

HIV-1 and HIV-2 dual infection: lack of HIV-2 provirus correlates with low CD4+ lymphocyte counts.

OBJECTIVE: We conducted this study to genetically characterize dual infection in individuals demonstrating a dual serological profile. METHODS: All subjects were first evaluated by immunoblot for antibody reactivity to the major viral antigens for HIV-1 and HIV-2. Sera were judged to be dual-seropositive if they reacted with strong and equal intensity with the envelope antigens of both HIV-1 and HIV-2 and were confirmed with type-specific recombinant env peptides. We used nested polymerase chain reaction (PCR) to amplify proviral gag and env sequence from peripheral blood mononuclear cell (PBMC) DNA from HIV-1- and HIV-2-infected individuals. Positive amplification was detected after Southern blot hybridization. RESULTS: Plasmid dilution and mixing showed equivalent sensitivity of HIV-1 and HIV-2 primers that was not altered by heterologous target sequences. The DNA PCR showed 100% sensitivity and specificity for detection of monotypic HIV infection. Serologically defined HIV-dual reactives were evaluated by this assay, with 100% detection in female sex workers (21 out of 21), but only 38.5% detection (five out of 13) in hospitalized patients; all being HIV-1 positive only. The lack of HIV-2 proviral signal was significantly correlated with low CD4+ lymphocyte counts (Pvalue = 0.04). CONCLUSION: The results suggest that HIV dual infection may not be a static condition. Levels of HIV-2 may decrease with disease progression or sequester in tissue reservoirs; our results may also suggest that HIV-1 effectively overgrows HIV-2 in the dually exposed host individual.

Sexually transmitted diseases and risk of HIV infection in men attending a sexually transmitted diseases clinic in Dakar, Senegal.

This cross-sectional study was carried out among male outpatients with symptoms of STDs at the STD reference centre at the Institute of Social Hygiene (IHS), Dakar, Senegal, from March 1989 through May 1991. This study was used to determine the prevalence of STDs and HIV among male patients attending an STD clinic and to identify their socio-demographic characteristics and risk factors. A total of 975 patients were enrolled in the study. The most common syndromes were urethritis (76%) and genital ulcers (22%). Considering single infections, the major STD agents were Neisseria gonorrheae (N.gonorrheae, 30%), Chlamydia trachomatis (C.trachomatis, 15%), Treponema pallidum (T.pallidum, 12%), and Haemophilus ducreyi (H.ducreyi, 7%). HIV prevalence was 2.6 percent (25/975). After multivariate analysis, the risk factors associated with HIV infection were a history of sex with prostitutes (odds ratio [OR] = 8.6, 95% confidence interval [CI] = 2.0-37.8), unprotected sexual contact (OR = 5.6, 95% CI = 1.2-25.0), a history of urethritis (OR = 3.4, 95% CI = 1.3-8.9), current STDs due to H.ducreyi or T.pallidum (OR = 6.1, 95% CI = 2-18.8), and mixed STD infection (OR = 5.3, 95% CI = 1.3-21.8). HIV prevalence was quite low in this population compared to similar studies of STD patients from other sub-Saharan African countries. Neisseria gonorrheae and Chlamydia trachomatis were the leading causes of STDs. A history of risky sexual behaviour, previous STDs, current genital ulcers, and mixed STD infections were associated with HIV infection. Further studies are necessary to determine changes in the relationship of STDs and HIV infection in this population.

Achieving an HIV vaccine: the need for an accelerated national campaign.

AIDS: The development of an effective HIV vaccine has become a crucial national healthcare goal. To develop a worldwide AIDS vaccine, an international collaboration with developing countries is needed. The global approach rationale is threefold: millions of lives can be saved, a vaccine preparation can be tested more rapidly and economically among populations with high rates of infections; and the HIV epidemic comprises at least ten different subtypes. Although a number of barriers to the successful development of an HIV vaccine exist, the polio vaccine can be used as an example to show researchers how to overcome the obstacles. Jonas Salk, the polio vaccine developer, used killed whole virus in a technique that critics argued would not be fully effective. However, the Salk vaccine reduced polio-related paralysis by 72 percent, while the more effective Sabin oral vaccine did not become available until several years later. The lesson to be learned is that any percent of effectiveness is better than nothing, and researchers should not abandon uncertain HIV vaccine development efforts because they believe a better solution may develop in the future. The existence of traditional research should not preclude the development of new solutions that might prove more effective. For example, in the case of polio, the March of Dimes campaign pushed both the Salk and Sabin vaccines despite the skepticism of many academic research groups.^ieng

Distinct quasi-species in the blood and the brain of an HIV-2-infected individual.

Sequences of the HIV-2 envelope C2-C3 region were obtained after direct PCR amplification of proviral DNA from the brain and peripheral blood mononuclear cells of an HIV-2-infected AIDS patient. Tissue-specific sequences confirmed previous observations that HIV-2 is indeed present in the central nervous system of infected individuals. Distinct but related quasi-species were present in these two different tissues of the same individual. Residues at position 18 and 19 of the V3 loop and overall charge of the loop suggest that the brain virus was NSI/macrophage tropic; whereas the sequences from the two blood samples were indicative of a SI/T-cell tropic virus. This is the first description of these two genotypes in the same HIV-2-infected individual. Analysis of more samples from different compartments would help to better understand tissue-specific factors in quasi-species evolution in vivo.

Lessons from the second AIDS virus, HIV-2.

PIP: Although the clinical signs and symptoms of human immunodeficiency virus (HIV)-2 are similar to those associated with HIV-1 infection, the former virus has a markedly lower perinatal transmission rate and heterosexual infectivity potential. An ongoing cohort study in Senegal, where the disease was first encountered a decade ago, of 136 HIV-2-infected women found an overall incidence of acquired immunodeficiency syndrome of only 0.18/100 person-years in 548 person-years of observation. Moreover, the rate of developing an abnormal CD4 lymphocyte count from the time of infection onward was 1%/year for HIV-2 infected women compared to 10% for HIV-1. In vitro studies of HIV-2 have shown reduced cell killing, less syncytia formation, and slower viral replication compared to HIV-1. It remains unclear whether viral features alone account for the long clinical latency period and different transmission dynamics of HIV-2. An interesting early finding of the Senegalese study is that partial protection from HIV-1 exists in those already infected with HIV-2. Further delineation of the mechanisms involved in this seeming protective effect should be a high research priority given the potential for prevention of the more virulent HIV-1 strain.^ieng