Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria.

BACKGROUND: While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. METHODS: We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. RESULTS: Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29-41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78-220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients retained through 84 months maintained ≥95% adherence. CONCLUSION: While improved access to HIV care and treatment remains a challenge in Nigeria, our study shows that a high quality of care was achieved as evidenced by strong long-term clinical, immunologic and virologic outcomes.

Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort.

BACKGROUND: Despite sparse efficacy data, tenofovir-emtricitabine or tenofovir-lamivudine plus nevirapine is used in many resource-constrained settings. METHODS: This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir-emtricitabine or lamivudine (tenofovir group) or zidovudine-lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. RESULTS: A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03-1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40-.63) and increasing age (HR, 0.98; 95% CI, .97-.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. CONCLUSIONS: Compared with zidovudine-lamivudine, the use of tenofovir-lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection.

Tuberculosis Incidence and Risk Factors Among Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy in a Large HIV Program in Nigeria.

Background. Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods. This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results. Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7-27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4(+) cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions. The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections.

Scale-up of networked HIV treatment in Nigeria: creation of an integrated electronic medical records system.

OBJECTIVES: The implementation of PEPFAR programs in resource-limited settings was accompanied by the need to document patient care on a scale unprecedented in environments where paper-based records were the norm. We describe the development of an electronic medical records system (EMRS) put in place at the beginning of a large HIV/AIDS care and treatment program in Nigeria. METHODS: Databases were created to record laboratory results, medications prescribed and dispensed, and clinical assessments, using a relational database program. A collection of stand-alone files recorded different elements of patient care, linked together by utilities that aggregated data on national standard indicators and assessed patient care for quality improvement, tracked patients requiring follow-up, generated counts of ART regimens dispensed, and provided 'snapshots' of a patient's response to treatment. A secure server was used to store patient files for backup and transfer. RESULTS: By February 2012, when the program transitioned to local in-country management by APIN, the EMRS was used in 33 hospitals across the country, with 4,947,433 adult, pediatric and PMTCT records that had been created and continued to be available for use in patient care. Ongoing trainings for data managers, along with an iterative process of implementing changes to the databases and forms based on user feedback, were needed. As the program scaled up and the volume of laboratory tests increased, results were produced in a digital format, wherever possible, that could be automatically transferred to the EMRS. Many larger clinics began to link some or all of the databases to local area networks, making them available to a larger group of staff members, or providing the ability to enter information simultaneously where needed. CONCLUSIONS: The EMRS improved patient care, enabled efficient reporting to the Government of Nigeria and to U.S. funding agencies, and allowed program managers and staff to conduct quality control audits.

Sputum smear concentration may misidentify acid-fast bacilli as Mycobacterium tuberculosis in HIV-infected patients.

BACKGROUND: Tuberculosis (TB) diagnosis in most resource-limited settings still depends on smear microscopy for identification of acid-fast bacilli (AFB). However, recently developed molecular diagnostics that test for the presence of Mycobacterium tuberculosis (Mtb) DNA have been shown to be superior for confirmation of TB diagnosis. METHODS: At regular clinical visits over a 12-month period, we collected sputa from HIV-infected patients presenting with signs or symptoms of TB at 2 Nigerian clinics. Sputa were stained for AFB and tested using the Genotype MTBDRplus to confirm the presence of Mtb. Other species were identified using 16S rRNA sequence. RESULTS: In 56% (233/415) of AFB-positive patients, Mtb was confirmed. The patients on antiretroviral therapy were less likely than those not on antiretroviral therapy to be infected with Mtb [odds ratio (OR) = 0.25, P = 0.003]. In a multivariate logistic regression model using clinical features and diagnostic results, abnormal respiratory findings on auscultation (OR = 3.28, P = 0.03) and a direct sputum smear grade >3/100 (OR = 6.4, 4.6, P < 0.02) were significant predictors of Mtb infection. Concentrated sputum smear was predictive of Mtb infection only at the highest grades (2+, 3+). Interestingly, among 65 samples that could not be confirmed for Mtb, 32 (49%) were found to contain other, possibly novel, actinomycetes, including atypical Mycobacteria, Rhodococcus spp, Nocardia spp, and Corynebacterium spp. CONCLUSIONS: We conclude that concentrated sputum smears may misidentify other bacteria as Mtb in HIV-infected patients. The use of molecular diagnostics could reduce unnecessary or inappropriate treatment and improve identification of pathogens in resource-limited settings with high HIV burden.

Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource-limited settings.

BACKGROUND: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria. METHODS: We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria. RESULTS: A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001). CONCLUSIONS: Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.

Twenty years of prospective molecular epidemiology in Senegal: changes in HIV diversity.

Over a 20-year period we have observed the dynamics of HIV-1 subtypes and HIV-2 infection in a prospective cohort of registered female sex workers (FSW) in Dakar, Senegal. Prevalence and incidence rates for HIV-1 and HIV-2 are described from 290 seroprevalent and 193 seroincident subjects who were among the 3,910 women enrolled between 1985 and 2004. We report a significant decrease of HIV-2 prevalence in the cohort, parallel to the introduction and rise of HIV-1 infection. In 328 HIV-1-infected women, a 385-bp C2-V3 fragment of the envelope gene was sequenced and classified into the following subtypes or recombinant forms: 239 (72%) were subtype A [of which 180 (55%) were CRF02_AG and 53 (16%) were A3], 10 (3%) were B, 12 (4%) were C, 11 (4%) were D, 18 (6%) were G, 24 (7%) were CRF06_cpx, and 7 (2%) were CRF09_cpx. We found an increasing proportion of CRF02_AG over many years, but recently subsubtype A3 has over-taken CRF02_AG, with the largest proportion of new infections. The predominance of existing HIV-1 subtypes did not preclude the emergence and increase of other closely related subtypes or recombinant forms. This 20-year prospective serological and sequence analysis of HIV viruses reveals a complex and changing HIV epidemic in Senegal.

Management of HIV-1 infection with a combination of nevirapine, stavudine, and lamivudine: a preliminary report on the Nigerian antiretroviral program.

OBJECTIVE: To evaluate treatment outcome in the first 12 months among HIV-positive patients managed with a combination of nevirapine + stavudine + lamivudine under the current national antiretroviral (ARV) program in Nigeria. DESIGN: This was a prospective observational, cohort study on 50 ARV-naive patients who met the inclusion criteria for the program and had given informed consent. All patients were in stage 2 or stage 3 periods of infection based on World Health Organization clinical classification. The patients were treated with the generic brands of ARVs and treatment consisted of oral nevirapine (Nevimal, Cipla, Mumbai, India), 200 mg daily, lamivudine (Lamivir, Cipla), 150 mg twice daily, and stavudine (Stavir, Cipla), 40 mg twice daily. Prior to initiation of treatment, the clinical history and baseline data for each patient were documented. The levels of plasma HIV-1 RNA, CD4 cell counts, frequency of opportunistic infections, and estimated body mass index were recorded at baseline and subsequently at intervals during treatment. Data obtained at the various sampling times for each parameter were compared against their baseline values. RESULTS: Data on the plasma HIV-1 RNA levels indicated that between baseline and week 24, the median viral load of the patients decreased by 1.79 log(10) copies/mL. Equally between baseline and week 48 the median CD4 cell counts increased by 186 x 10(6) cells/L, the frequency of opportunistic infections decreased by 82%, the median body mass index increased by 4.8 kg/m(2), and 36% experienced side effects, which were minor and transient. The most prevalent side effect recorded was skin rash associated with nevirapine. Good adherence to this triple regimen was recorded in >85% of the patients. CONCLUSIONS: The overall results within the 12-month treatment period indicated an effective suppression of viral replication, the reconstitution of the immune system, and improvement of the physical well-being of the study population. Though there may be differences in global distribution of the infecting HIV-1 subtypes, the clinical and biologic results of this study compared favorably to those documented in cohorts treated with branded and generic ARV drugs in some developed and developing countries. The cumulative data in this study further confirmed that the correct use of generic brands of ARVs is a feasible option in HIV care and support programs in resource-poor countries.

Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

BACKGROUND: Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. METHODS: Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. RESULTS: The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. CONCLUSION: Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

Molecular epidemiology of human immunodeficiency virus type 1 sub-subtype A3 in Senegal from 1988 to 2001.

The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001. We also found that HIV-1 A3 is not confined to the FSW cohort in Senegal but is also circulating in the general population in Dakar. Furthermore, analyses of viral sequences from a few other West and Central African countries also demonstrated evidence of HIV-1 A3 sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of sub-subtype A3 in the general population in Senegal, as well as in a few neighboring West and Central African countries, along with the increasing incidence of infection with A3-containing viruses in the Dakar high-risk FSW population, we feel that HIV-1 sub-subtype A3 viruses are important to distinguish and monitor.

Highly active antiretroviral therapy and viral response in HIV type 2 infection.

Human immunodeficiency virus type 2 (HIV-2), the second human retrovirus known to cause AIDS, is endemic to West Africa but is infrequently found outside this region. We present a case series of 10 HIV-2--infected individuals treated in the United States. Physicians applied the principles of highly active antiretroviral therapy (HAART), normally used in treating HIV type 1, with modifications considered appropriate for treating HIV-2. CD4+ cell count, HIV-2 virus load, and clinical status were found to correlate well, providing evidence that HIV-2 virus load is useful in managing treatment of patients with HIV-2 who are receiving therapy. However, HAART regimens with predicted efficacy for treatment of HIV type 1 infection are not as efficacious for treatment of HIV-2. Controlled clinical trials of HIV-2-infected patients receiving various HAART regimens are needed to provide therapeutic guidance to the medical community.

Widespread distribution of antisense transcripts in the Plasmodium falciparum genome.

The availability of the complete genome sequence of Plasmodium falciparum has facilitated high-throughput profiling of its complex life cycle, following the application of micro-array, proteomic, and serial analysis of gene expression (SAGE) technologies in this system. These, in turn, have yielded unprecedented insight into global gene expression, including the foremost demonstration of antisense transcription in the parasite. For example, owing to its inherent ability to sample novel ORFs and to predict transcript orientation, SAGE analysis in asexual forms led to the initial discovery of highly abundant antisense RNAs. To determine the extent of this phenomenon in P. falciparum, we have surveyed the distribution of both sense and antisense transcripts across the asexual transcriptome for the first time. To this end, a relational database integrating SAGE expression data with genome annotation information was constructed. This allowed the comprehensive annotation of a total of 17245 SAGE tags, extending over a 350-fold expression range. Transcripts from approximately 30% of the estimated 3D7 gene loci were present at detectable levels in mixed asexual stages, where loci involved in invasion and immune evasion; and carbohydrate metabolism were highly represented in the sense transcriptome. Approximately 12% of SAGE tags, however, were derived from the non-coding strand of nuclear-encoded ORFs, indicating that endogenous antisense RNAs are widespread in this system. Notably, these antisense transcripts were absent from the mitochondrial genome. Interestingly, we note that sense and antisense tag counts from single loci across the transcriptome were inversely related. Taken together, this data may provide first hints as to the possible function of antisense transcription in this system.

Drug-induced alterations in gene expression of the asexual blood forms of Plasmodium falciparum.

The complete genome sequence of the malarial parasite, Plasmodium falciparum [Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., and Hyman, R.W. (2002) Nature 419: 498-510; Hyman, R.W., Fung, E., Conway, A., Kurdi, O., Mao, J., Miranda, M. et al. (2002) Nature 419: 534-537], has provided researchers with the informational base for establishing genomic [Volkman, S.K., Hartl, D.L., Wirth, D.F., Nielsen, K.M., Choi, M., Batalov, S., et al. (2002) Science 298: 216-218], proteomic [Florens, L., Washburn, M.P.J.D.R., Anthony, R.M., Grainger, M., Haynes, J.D., et al. (2002) Nature 419: 520-526; Lasonder, E., Ishihama, Y., Anderson, J.S., Vermunt, A.M.W., Pain, A., Sauerwein, R.W., et al. (2002) Nature 419: 537-542] and genome-wide RNA expression [Ben Mamoun, C., Gluzman, I.Y., Hott, C., MacMillan, S.K., Amarakone, A.S., Anderson, D.L., et al. (2001) Mol Microbiol 39: 26-36; Hayward, R.E., Derisi, J.L., Alfadhli, S., Kaslow, D.C., Brown, P.O., and Rathod, P.K. (2000) Mol Microbiol 35: 6-14] analyses in this system. In fact, we have previously utilized SAGE (serial analysis of gene expression) to identify abundant loci that probably constitute part of the active metabolome [Patankar, S., Munasinghe, A., Shoaibi, A., Cummings, L.M., and Wirth, D.F. (2001) Mol Biol Cell 12: 3114-3125], as well as to characterize antisense transcription on a global scale in Plasmodium. In the present study, the comprehensive annotation of SAGE libraries derived from an asexual stage population exposed to drug and its matched control was used to assess the modulation of gene expression by chloroquine. Here, we observed a constellation of changes, with the differential regulation of over 100 transcripts, and have confirmed the data by alternate methods. A few responsive loci, including PfMDR1, have previously been implicated in the mechanism of chloroquine action/resistance. Several others, however, were derived from unexpected categories, including a large number of unknown open reading frames (ORFs), whose induction after drug exposure may provide first hints to their possible function.

Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal.

From a prospective cohort study of 1948 initially human immunodeficiency virus (HIV) uninfected female commercial sex workers followed between 1985 and 1999 in Dakar, Senegal, the authors compared the male to female per infectious sexual exposure transmission probability of HIV types one (HIV-1) and two (HIV-2). New non-parametric competing risks failure time methods were used, which minimized modelling assumptions and controlled for risk factors for HIV infection. The HIV-1 versus HIV-2 infectivity ratio over time was estimated by the ratio of smoothed non-parametric kernel estimates of the HIV-1 and HIV-2 infection hazard functions in sex workers, adjusted by an estimate of the relative HIV-1 versus HIV-2 prevalence in the partner population. HIV-1 was found to be significantly more infectious than HIV-2 throughout the follow-up period (P < 0.001). The HIV-1/HIV-2 infectivity ratio was inferred to be approximately constant over time, with estimated common value 3.55. The finding of greater HIV-1 infectivity persisted in sensitivity analyses and in covariate-adjusted analyses, with adjusted infectivity ratio estimates ranging between 3.40 and 3.86. Understanding the mechanisms by which HIV-1 infects more efficiently than HIV-2 may be useful in the development of HIV-1 vaccines. Additionally, the methodology developed here may be useful for analysing other data sets.

Intrapatient diversity and its correlation with viral setpoint in human immunodeficiency virus type 1 CRF02_A/G-IbNG infection.

The human immunodeficiency virus type 1 (HIV-1) viral setpoint during the disease-free interval has been strongly associated with future risk of disease progression. An awareness of the correlation between viral setpoint and HIV-1 genetic evolution over time is important in the understanding of viral dynamics and infection. We examined genetic diversity in HIV-1 CRF02_A/G-IbNG-infected seroincident women in Dakar, Senegal; determined whether a viral setpoint kinetic pattern existed for CRF02_A/G-IbNG during the disease-free interval; and correlated viral load level and diversity. Samples were drawn during the disease-free interval from consenting CRF02_A/G-IbNG-infected, antiretroviral therapy-naïve female commercial sex workers in Dakar, Senegal. Based on sequential plasma RNA values, low and high viral setpoint groups were established. Intrapatient diversity and divergence over time was determined from earlier and later time point DNA samples from each person. Most individuals followed the viral setpoint paradigm. For each 1/-/log(10) copy/ml of plasma increase in viral load, intrapatient diversity increased by 1.4% (P = 0.028). A greater diversification rate was observed in the high viral setpoint group than in the low viral setpoint group (P = 0.01). Greater nucleotide (P = 0.015) and amino acid (P = 0.048) divergences and a greater nucleotide divergence rate (P = 0.03) were found in the high viral setpoint group. There was no difference between the groups in the ratio of the number of nonsynonymous substitutions per nonsynonymous site to the number of synonymous substitutions per synonymous site. The greater intrapatient diversity, divergence, and diversification rates observed in the high viral setpoint group supports the notion that diversity is driven by cycles of viral replication resulting in accumulated mutations. Recognizing diversity potential based on viral load levels in individuals may inform the design of vaccines and therapies.

Associations between MHC class I and susceptibility to HIV-2 disease progression.

OBJECTIVES: Human immunodeficiency virus type 2 (HIV-2) progression to disease is significantly slower than that of human immunodeficiency virus type 1 (HIV-1). Genetic determinants for susceptibility to disease progression were hypothesized to play a more significant role in this infection compared with HIV-1. We sought to identify common human lymphocyte antigen (HLA) alleles in the Senegalese population and to compare HLA profiles between HIV-2-infected individuals with low and high risk for disease progression. STUDY DESIGN/METHODS: We conducted a case-control study investigating possible associations between MHC class I genes and the risk of disease progression in HIV-2-infected individuals. The MHC class I genotype was molecularly defined using polymerase chain reaction with sequence specific primers (PCR-SSP) in 62 female sex workers from the Dakar, Senegal cohort. Lack of antibodies to the HIV-2 antigen p26 has been previously shown to predict disease progression and was used in this study as a surrogate marker. Twenty-one cases were identified lacking antibodies to p26, therefore at a higher risk of disease progression, and were compared with 41 p26 antibody-positive, randomly selected controls. RESULTS: Statistical analysis showed that HLA B35 was significantly associated with lack of p26 antibodies, and higher risk of disease progression ( < 0.05). The same association was found for the self-defined class I haplotypes B35-Cw4 and A23-Cw 7 ( < 0.05). The HLA B 53 allele was associated with slower disease progression; however, this association was not statistically significant. We observed a trend whereby heterozygotes were at lower risk for HIV-2 disease progression, as previously reported in HIV-1 disease. CONCLUSIONS: In this West African population, a distinct profile of HLA class I alleles was observed, and many of these appear to influence disease progression in HIV-2 infection.