Antiretroviral regimens in pregnancy and breast-feeding in Botswana.

BACKGROUND: The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS: We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS: The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS: All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)

Safety and efficacy of nevirapine- and efavirenz-based antiretroviral treatment in adults treated for TB-HIV co-infection in Botswana.

BACKGROUND: The safety and efficacy of nevirapine (NVP) and efavirenz (EFV) based highly active antiretroviral treatment (ART) with concurrent anti-tuberculosis treatment in sub-Saharan Africa has not been well established. METHODS: We performed a retrospective study comparing human immunodeficiency virus (HIV) infected adults exposed and not exposed to tuberculosis (TB) treatment with similar baseline HIV-1 RNA levels who were started on ART as part of Botswana's ART Programme. ART regimens, HIV-1 RNA, CD4+ cell count, and liver function tests were reviewed for 12 months following ART initiation. RESULTS: Among 155 patients on ART only and 155 exposed to TB treatment, there was no difference in virologic or immunologic response throughout the first year of ART. Furthermore, there remained no differences in virologic or immunologic outcomes when NVP and EFV groups were stratified by TB treatment exposure status. While more hepatotoxic events occurred in the group exposed to TB treatment than in those not exposed (9% vs. 3%, P = 0.05), there was no difference between patients treated with NVP and those treated with EFV. CONCLUSIONS: Patients co-infected with HIV and TB in Botswana can be treated effectively with either NVP- or EFV-based ART and TB treatment. As hepatotoxic events were more common in the group exposed to TB treatment, liver function tests should be monitored closely.

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.

Gene-expression profiling of HIV-1 infection and perinatal transmission in Botswana.

Perinatal transmission of human immunodeficiency virus (HIV)-1 represents a major problem in many regions of the world, especially Southern Africa. With the exception of viral and proviral load, the role for maternal cofactors in perinatal transmission outcome is largely unknown. In this study, an assessment was made of peripheral blood mononuclear cells (PBMC) gene-expression profiles to better understand transcriptional changes associated with HIV-1 infection and perinatal transmission among young adult mothers with infants in Botswana. Peripheral blood mononuclear cells specimens were used from 25 HIV+ drug naive and 20 HIV- healthy mothers, similar in age and location, collected in 1999-2000 and 2003, and processed with the exact same methods, as previously described. Expression profiling of 22 277 microarray gene probes implicated a broad initiation of innate response gene-sets, including toll-like receptor, interferon-stimulated and antiviral RNA response pathways in association with maternal HIV-1 infection. Maternal transmission status was further associated with host genes that influence RNA processing and splicing patterns. In addition to real-time polymerase chain reaction validation of specific genes, enriched category validation of PBMC profiles was conducted using two independent data sets for either HIV-1 infection or an unrelated RNA virus, severe acute respiratory virus infection. HIV-1 pathogen-specific host profiles should prove a useful tool in infection and transmission intervention efforts worldwide.

Male circumcision: an acceptable strategy for HIV prevention in Botswana.

BACKGROUND: Male circumcision is known to reduce the risk of acquiring HIV, but few studies have been performed to assess its acceptability among either children or adults in sub-Saharan Africa. METHODS: We conducted a cross sectional survey in nine geographically representative locations in Botswana to determine the acceptability of male circumcision in the country, as well as the preferred age and setting for male circumcision. Interviews were conducted using standardised questionnaires both before and after an informational session outlining the risks and benefits of male circumcision. RESULTS: Among 605 people surveyed, the median age was 29 years (range 18-74 years), 52% were male, and >15 ethnicities were represented. Before the informational session, 408 (68%) responded that they would definitely or probably circumcise a male child if circumcision was offered free of charge in a hospital setting; this number increased to 542 (89%) after the informational session. Among 238 uncircumcised men, 145 (61%) stated that they would definitely or probably get circumcised themselves if it were offered free of charge in a hospital setting; this increased to 192 (81%) after the informational session. In a multivariate analysis of all participants, people with children were more likely to favour circumcision than people without children (adjusted odds ratio 1.8, 95% CI 1.0 to 3.4). Most participants (55%) felt that the ideal age for circumcision is before 6 years, and 90% of participants felt that circumcision should be performed in the hospital setting. CONCLUSIONS: Male circumcision appears to be highly acceptable in Botswana. The option for safe circumcision should be made available to parents in Botswana for their male children. Circumcision might also be an acceptable option for adults and adolescents, if its efficacy as an HIV prevention strategy among sexually active people is supported by clinical trials.

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.

Molecular epidemiology of genital Chlamydia trachomatis infection in high-risk women in Senegal, West Africa.

The prevalence and heterogeneity of Chlamydia trachomatis infections in a cohort of female sex workers in Dakar (Senegal) were determined by using endocervical-swab-based PCR DNA amplification assays. The overall prevalence of cervical chlamydial infection was 28.5% (206 of 722), and most of these infections were asymptomatic. An increased number of sexual partners was significantly associated with infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.06 to 1.77), while the presence of a yeast infection was negatively associated with chlamydial infection (AOR = 0.28; 95% CI = 0.10 to 0.83). Six different C. trachomatis genotypes were identified based on phylogenetic analysis of the omp1 gene sequences. Interestingly, genotype E predominated (47.6%) and was not associated with visible signs of cervical inflammation compared to non-E genotypes (P < 0.05). Overall, the high rate of asymptomatic C. trachomatis infection by genotype E may suggest genotype-specific properties that confer a transmission advantage in this high risk population.

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.

Epstein-Barr virus in Hodgkin's disease: correlation of risk factors and disease characteristics with molecular evidence of viral infection.

Risk factors suggestive of relatively late exposure to EBV have been consistently associated with Hodgkin's disease (HD) in younger adults. In addition, evidence of EBV infection has been found in the Reed-Sternberg cells themselves in about one-third to one-half of all HD cases. However, no study yet published has correlated these childhood social environment risk factors with the presence of EBV in Hodgkin's tumor cells. We examined whether EBV-positive HD occurs in those patients whose childhood environment would predispose them to relatively late exposure to EBV. The study population consisted of 102 cases of mixed cellularity (MC; n = 25) or nodular sclerosing (n = 77) HD. Samples that tested positive for either EBV-encoded RNA or latent membrane protein or both were considered EBV-positive. Of the 102 cases, 83 completed a questionnaire regarding childhood social environment. The association with EBV-positivity was estimated by the odds ratio (OR) with 95% confidence intervals (CI). Twenty-two percent of the cases were EBV-positive. These cases were more likely to be MC (OR, 6.2; CI, 2.3-16.3) and male (OR, 3.4; CI, 1.3-9.0). History of infectious mononucleosis (IM) was not predictive of EBV-positivity, with only 3 of 14 such patients being EBV-positive (P = 0.82). Contrary to our hypothesis, no association between EBV and childhood environment risk factors was identified. The association of EBV with MC histology and male gender agrees with previous reports. The most intriguing finding was the dissociation between IM history and EBV-positivity, in that almost all of the cases with a history of IM were EBV-negative.

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.

Diagnosis of sexually transmitted infections in female prostitutes in Dakar, Senegal.

OBJECTIVE: To study the validity and performance of a number of rapid indicators for the diagnosis of sexually transmitted infections (STIs) in female prostitutes in Dakar, Senegal; characteristics of these indicators were rapidly obtainable, easy to perform, accurate, useful at district level, and reasonable cost. METHODS: An STI prevalence study in female prostitutes (n = 374) seen at the STD clinic in Dakar, Senegal was done; a history, clinical examination, simple laboratory tests, and "gold standard" microbiological tests were performed. For a number of sociodemographic data, actual or past symptoms of STI, clinical signs, and rapid laboratory tests, validity variables, performance characteristics, and likelihood ratios for detection of gonococcal or chlamydial cervical infection were determined. RESULTS: Cervical infection (chlamydial or gonococcal) was present in 24.9% of prostitutes; 46% had trichomoniasis and 29.4% had syphilis. Young age, abnormal vaginal discharge, endocervical mucopus, a positive leucocyte esterase test on urine, and 10 or more leucocytes in Gram stained smears of vaginal, cervical, or urine samples were significantly associated with cervical STI. Some of the rapid indicators had high sensitivity, others high specificity but none had acceptable overall validity. None of the indicators had at the same time a sensitivity above 50% and a positive predictive value above twice the background prevalence of cervical infection. 10 or more leucocytes in the cervical smear had a likelihood ratio of 1.83 increasing pretest probability of 24.9% to post-test probability of 38%, the best result obtained by any of the rapid indicators. CONCLUSIONS: Rapid indicators of cervical STIs are insufficiently valid, which largely restricts their usefulness to high STI prevalence situations for instance, in prostitute populations and in STD patient management.

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.

Natural protection against HIV-1 infection provided by HIV-2.

Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in a cohort of commercial sex workers. Despite a higher incidence of other sexually transmitted diseases (STDs), HIV-2-infected women had a lower incidence of HIV-1 than did HIV-seronegative women, with a relative risk of 0.32 (P = 0.008). An understanding of the cross-protective mechanisms involved may be directly relevant to HIV-1 vaccine development.

Reduced rate of disease development after HIV-2 infection as compared to HIV-1.

Human immunodeficiency virus type-2 (HIV-2) is a close relative of the prototype acquired immunodeficiency syndrome (AIDS) virus, HIV-1. HIV-2 is biologically similar to HIV-1, but information is lacking concerning clinical outcomes of HIV-2-infected individuals. From 1985 to 1993, a prospective clinical study was conducted in women with HIV-2 and HIV-1 infection to determine and compare rates of disease development. HIV-1-infected women had a 67% probability of AIDS-free survival 5 years after seroconversion in contrast with 100% for HIV-2-infected women. In addition to having significantly less HIV-related disease outcome in HIV-2 enrollees compared to HIV-1 enrollees, the rate of developing abnormal CD4+ lymphocyte counts with HIV-2 infection was also significantly reduced. This natural history study demonstrates that HIV-2 has a reduced virulence compared to HIV-1.

Slower heterosexual spread of HIV-2 than HIV-1.

Because of the similar virological properties of HIV types 1 and 2, HIV-2 was assumed to be as infectious and capable of inducing AIDS as HIV-1. Seroepidemiological studies have shown significant rates of HIV-2 infection in West Africa, and surveys from other regions of the world indicate that the spread of HIV-2 infection continues. However the pathogenic potential of HIV-2 is considered to be lower than that of HIV-1. It is therefore important to understand the transmission properties of HIV-2 and its contribution to the AIDS pandemic. Since 1985, we have prospectively studied 1452 registered female prostitutes in Dakar, Senegal, with sequential evaluation of their antibody status to HIV-1 and HIV-2. During the study the overall incidence of HIV-1 and HIV-2 was the same (1.11 per 100 person-years of observation [pyo]). However, the annual incidence of HIV-1 increased substantially: there was a 1.4-fold increased risk per year and thus a 12-fold increase in risk over the entire study period. The incidence of HIV-2 remained stable, despite higher HIV-2 prevalence. In our population the heterosexual spread of HIV-2 is significantly slower than that of HIV-1, which strongly suggests differences in the viruses' infectivity potential.

PIP: Between February 1985 and February 1993 in Dakar, Senegal, the Social Hygiene Clinic screened 1452 registered female prostitutes (5608 samples) for sexually transmitted diseases, including HIV-1 and HIV-2. The overall prevalence rate stood at 11.3% for HIV-2 while it was 6.2% for HIV-1. 12 women (0.8%) tested positive for HIV-1 and HIV-2. Health workers followed the 1277 women who were initially HIV seronegative to determine seroconversion. 46 of these women seroconverted to HIV-2 and another 46 seroconverted to HIV-1. Overall incidence of HIV-2 and HIV-1 was 1.11 per person years of observation (pyo). Eight women (incidence = 0.19 per 100 pyo) seroconverted to both HIV-2 and HIV-1. When the researchers controlled for age, nationality, years of registered prostitution, calendar year, and time in study, the relative risk for HIV-2 infection each year did not change. On the other hand, there was a significant 1.43 annual increase in the risk for HIV-1 infection (p .002), indicating a 12-fold increase in the risk of HIV-1 infection over the study period. These findings suggest that the 2 viruses have a distinctly different in-vivo biology and that HIV-2 has a lower infectivity than does HIV-1.