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Background Programmatic treatment outcome data for people living with human immunodeficiency virus type 2 (HIV-2) in West Africa, where the virus is most prevalent, are scarce. Methods Adults with HIV-2 initiating or receiving antiretroviral therapy (ART) through the Senegalese national AIDS program were invited to participate in this prospective, longitudinal observational cohort study. We analyzed HIV-2 viral loads, CD4 cell counts, antiretroviral drug resistance, loss to follow-up, and mortality. We also examined changes in treatment guidelines over time and assessed progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV-2. Results We enrolled 291 participants at 2 sites for 926.0 person-years of follow-up over 13 years. Median follow-up time was 2.2 years per participant. There were 21 deaths reported (7.2%), and 117 individuals (40.2%) were lost to follow-up, including 43 (14.7%) who had an initial visit but never returned for follow-up. CD4 counts and HIV-2 viral suppression ( Conclusions Participants in the Senegalese national AIDS program are initiating ART earlier in the course of disease, and more modern therapeutic regimens have improved outcomes among those receiving therapy. Despite these achievements, HIV-2 treatment remains suboptimal, and significant challenges to improving care remain.

Les Journees scientifiques du site ANRS du Senegal se sont deroulees du 3 au 5 juin 2014 a l’hotel des Almadies de Dakar. Habituellement organisees tous les deux ans pour presenter les resultats des travaux de recherche et discuter des orientations strategiques pour les annees a venir, elles ont revetu cette annee une importance particuliere, avec la celebration du vingtieme anniversaire du site ANRS du Senegal et l’organisation d’un atelier regional avec Onusida.L’Atelier [...]

The ANRS Cohort 1215 brought together the first 400 patients receiving antiretroviral treatments through the government program for ARV treatment in Senegal. These people, infected with HIV-1, began their treatment between 1998 and 2002; they were treated with 2 NRTI + 1 PI or NNRTI. This prospective observational cohort received follow-up over the course of 12 years, from 1999 to 2010, and was one of the earliest established cohorts in Africa and providing the longest duration of ART follow-up. A series of interdisciplinary studies was conducted among these patients to assess the medical and social as well as the individual and collective impact of these treatments over the long term. This article presents the cohort's key methodological characteristics.

Background: In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses, and inform decisions. Methods: We pooled data from 13 research cohorts in 5 sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire, and Senegal) and 2 Asian (Cambodia and Laos) countries. HIV-infected adults (18 years and older) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results: Overall 3917 adults (62% women) on ART were followed up during 10,154 person-years. In the

OBJECTIVE The use of didanosine (ddI) in first-line antiretroviral therapy has been recently promoted for resource-limited settings. We therefore compared the long-term effectiveness and safety of the regimen combining ddI, lamivudine, and efavirenz or nevirapine with that of the WHO-recommended regimen of zidovudine (ZDV), lamivudine, and efavirenz or nevirapine in antiretroviral-naive patients in Senegal. METHODS Observational cohort study of patients enrolled between January 2000 and April 2002 in the Senegalese antiretroviral drug access initiative. Multivariate analyses were performed to compare, between the ddI and ZDV groups, the proportion of patients with a viral load 0.3). The rate of death tended to be higher in the ddI group (P = 0.06). ddI was less commonly discontinued than ZDV (P = 0.03). CONCLUSION The combination of ddI, lamivudine, and efavirenz or nevirapine resulted in sustained viral suppression and immunological recovery.

Summary CD4+ lymphocytes are a primary target of the human immunodeficiency virus (HIV), and CD4 counts are one of the factors used to measure disease progression in HIV-positive individuals. CD4 counts vary in uninfected individuals and across populations due to a variety of demographic, environmental, immunological and genetic factors that probably persist throughout the course of HIV infection. This study sought to determine reference levels and identify factors that influence lymphocyte counts in 681 HIV-uninfected adults in Senegal, where residents are exposed to a variety of infectious diseases and other conditions that may affect CD4 counts. Lymphocyte counts were assessed in commercial sex workers, symptomatic men and women presenting to the University of Dakar infectious disease clinic for out-patient care and women seeking family planning services. CD4 and CD3 lymphocyte counts differed between the four study groups (P

The objectives were to assess long-term adherence of the first HIV-1 patients receiving highly active antiretroviral therapy (HAART) in Senegal and to identify the main determinants of adherence. The first 180 patients enrolled in the Senegalese HAART initiative between August 1998 and April 2001 followed up for at least 30 days were eligible. Adherence was assessed monthly at each drug dispensation between November 1999 and November 2006 by a pharmacist using a pill count completed by a questionnaire. Adherence was expressed as the proportion of tablets taken to prescribed tablets. An adherence of 95% was considered to be good. A random-intercept logit model was fitted to identify the main determinants of adherence. Adherence data were available for 158 of 167 eligible patients. Twenty-nine patients died during the study period and 10 were lost to follow-up. Median treatment duration was 78 months accruing to 6657 person-months of observation. Overall mean adherence reached 91% [median: 100% interquartile range (IQR) 96-100%] and adherence exceeded 95% in 78% [95% CI 77-79%] of observations. After 4 years of treatment mean adherence stabilized around 90% and adherence >/= 95% stabilized around 70%. Treatment duration and protease inhibitor (PI)-based regimen (indinavir) had a negative effect on adherence but adherence tended to improve with time for patients receiving a PI. Patient-level variance was highly significant and accounted for a third of total variance. This work demonstrates that good long-term adherence can be achieved in the sub-Saharan context given close monitoring and adherence support measures confirms the worse adherence for indinavir and underlines the importance of patient heterogeneity. (authors)

Dual infection with HIV-1 and HIV-2 can occur in locales where these viruses co-circulate, most commonly in West Africa. Although dual seropositivity is common in this region, the true rate of dual infection remains unclear. In addition, whether unique HIV-1 subtypes are circulating in dually infected individuals is unknown. A cohort of 47 HIV-1 and HIV-2 dually seropositive individuals from Senegal, West Africa was screened for the presence of HIV-1 and HIV-2 gag and env PBMC viral DNA sequences using PCR. Of the 47 dual HIV-1/HIV-2 seropositive individuals tested, 19 (40.4%) had infection with both HIV-1 and HIV-2 confirmed by genetic sequence analysis, whereas only HIV-1 or HIV-2 was confirmed in 17 (36.2%) or 9 (19.1%), respectively. The majority of HIV-1 subtypes found were CRF-02 and A, although subtypes D, C, G, J and B were also found, reflecting the subtypes known to be circulating in Senegal. There was no significant difference in HIV-1 subtype distribution between individuals with confirmed dual infection and patients in this study with dual seropositivity but lacking HIV-2, or with HIV-1 infected patients within the general population in Senegal, although the study was underpowered to detect anything but large differences. The prevalence of HIV-1/HIV-2 dual infection appears to be significantly less than that of dually seropositive individuals and this likely reflects cross-reactive serology. The common HIV-1 subtypes prevalent in West Africa (CRF-02 and subtype A) have a similar distribution to those found in our cohort of dually infected and dually seropositive subjects.

In a polygamous marriage in Senegal, the husband and his two spouses were infected with HIV-1 group O. This study provides new full-length genome sequences for the two spouses (99SE-MP1299 and 99SE-MP1300) and the 3'-end LTR-tat fragment (6084 bp) for the husband (98SE-42HALD). Phylogenetic tree and diversity plot analysis revealed that the new viruses belong to HIV-1 group O and that they are closely related to each other in a cluster around ANT-70. The intrafamilial transmission occurred at most 6 years ago. The interpatient variability was highest in the envelope region, and in some regions of the envelope the strains from the two spouses do not cluster together anymore. The source of infection was in Cameroon and confirms a slow but continuous spread of HIV-1 group O viruses.

The aim was to assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults. A randomized double-blind placebo-controlled clinical trial was carried out in the urban community of Dakar Senegal. Eligibility criteria were age greater than 15 years HIV-1 or HIV-1/HIV-2 dual seropositivity CD4 cell count lower than 400 copies/cu. mm no progressive infection no previous history of intolerance to sulphonamide lack of severe anemia or neutropenia and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia cerebral toxoplasmosis bacterial pneumonia infectious enteritis bacterial meningitis urinary tract infection bacterial otitis and sinusitis and pyomyositis. Between September 1996 and March 1998 297 patients were screened and 100 were randomized in the study. Demographic clinical and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84%; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13) or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.57-2.13) or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2). The authors study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar Senegal. (authors)

A total of 343 HIV-1-positive samples obtained between June 1996 and March 1999 was genetically characterized in the envelope region by HMA and/or sequencing. The env subtype distribution was as follows: 290 (84.6%) A, 22 (6.5%) B, 16 (4.7%) C, 8 (2.5%) D, 1 (0.03%) E, 1 (0.03%) F1, 4 (1.2%) G, and 1 (0.03%) H. For 77 samples the p24 region from the gag gene was also sequenced, and for 9 (11.6%) the subtypes between env and gag were different. Phylogenetic tree analysis showed the predominance of AG-IBNG-like viruses among gag and env subtype A sequences. HMA is relatively simple and requires less sophisticated technical facilities compared with sequencing, and in Senegal 323 (94.2%) of the 343 samples could be identified by this technique. However, in the actual configuration of the assay, discrimination between the recombinant AG-IBNG-like recombinant viruses, which are predominant in Senegal, and the nonrecombinant subtype A viruses is not possible.

International audience

Fin 2013, 11 millions de PVVIH recevaient des ARV en Afrique ; la mise en application de la recommandation de l’OMS de traiter plus précocement (à partir de 500 CD4/mm3) devrait encore accroitre cet effectif. Actuellement, les deux tiers des patients en Afrique reçoivent leur traitement depuis moins de 5 ans, moins de 10 % sont traités depuis 8 ans au plus. Le recul historique est limité; l’impact à long terme des traitements est encore mal connu. Cet article passe en revue les connaissances acquises sur la période des 10 premières années de mise en oeuvre de la stratégie d’accès universel (2003–2013) en Afrique, en focalisant l’attention sur la prise en charge des adultes et en privilégiant une approche centrée sur les patients. Il s’appuie sur une revue de la littérature documentant les conséquences à long terme des traitements ARV. L’objectif est de rendre compte de l’intrication des aspects biologiques et sociaux, individuels et collectifs, qui influent sur la vie des PVVIH et conditionnent l’impact des traitements ARV dans la longue durée. Les aspects biomédicaux et sociaux sont abordés successivement au travers des résultats les plus significatifs. Les principales connaissances acquises sur le devenir à long terme des PVVIH traitées par ARV apportent des informations essentielles sur les conditions et adaptations des dispositifs de prise en charge nécessaires pour garantir le maintien du bénéfice des traitements dans le temps.

Comprehensive studies of 92 commercial sex workers in Senegal, Africa included an oral examination in which we obtained measurements of decayed, missing, and filled (DMF) teeth; plaque index; gingival index; recession; probing depth (PD); clinical attachment loss (CAL); and the presence of HIV-associated periodontal lesions, under conditions wherein the examiner was unaware of the subject's HIV status. Twenty-seven subjects (29%) were HIV seropositive, 19 of whom were positive for HIV-1, 7 positive for HIV-2, and 1 positive for both. Most subjects were not taking any medications and previous dental care was limited. HIV-seronegative and HIV-seropositive subjects were similar in mean age, number of DMF teeth, percentage of sites with visible plaque, and number of sites with recession. However, the frequency of sites with gingival bleeding, with PD > or = 6 mm, and with CAL > or = 6 mm was significantly greater in seropositive than seronegative subjects. No differences were observed between HIV-1 and HIV-2 positive subjects. About 26% of HIV-seropositive subjects and about 5% of the seronegative subjects exhibited at least one site with concurrent PD > or = 6 mm and CAL > or = 6 mm. HIV-associated periodontal lesions were seen in 3 HIV-seropositive subjects (2 linear gingival erythema, 1 necrotizing periodontitis). One HIV-seronegative subject exhibited necrotizing gingivitis. In this population with multiple risks to oral health, both HIV-1 and HIV-2 infections were associated with a significantly increased prevalence of periodontal disease.

Objective: Dual infection with HIV-1 and HIV-2, which is not uncommon in West Africa, has implications for transmission, progression, and antiretroviral therapy (ART). Few studies have examined viral dynamics in this setting. Our objective was to directly compare HIV-1 and HIV-2 viral loads and to examine whether this relationship is associated with CD4 + cell count. Study design: This is a retrospective analysis of data from observational cohort studies. Methods: We compared HIV-1 and HIV-2 viral loads from 65 dually infected, ART-naive Senegalese individuals. Participants provided blood, oral fluid, and cervicovaginal lavage (CVL) or semen samples for virologic and immunologic testing. We assessed relationships between HIV-1 and HIV-2 levels using linear regression with generalized estimating equations to account for multiple study visits. Results: After adjusting for CD4 + cell count, age, sex, and commercial sex work, HIV-1 RNA levels were significantly higher than HIV-2 levels in semen, CVL, and oral fluids. Despite similar peripheral blood mononuclear cell DNA levels among individuals with CD4 + cell counts above 500 cells/μl, individuals with CD4 + cell counts below 500 cells/μl had higher HIV-1 and lower HIV-2 DNA levels. Individuals with high CD4 + cell counts had higher mean HIV-1 plasma RNA viral loads than HIV-2, with HIV-1 levels significantly higher and HIV-2 levels trending toward lower mean viral loads among individuals with low CD4 + cell counts. Conclusion: Our data are consistent with the hypothesis that with disease progression, HIV-1 outcompetes HIV-2 in dually infected individuals. This finding helps explain differences in prevalence and outcomes between HIV-1, HIV-2, and HIV-dual infection.

To determine the effect of HIV-1 and HIV-2 infection on the prevalence of cervical human papillomavirus (HPV) and squamous intraepithelial lesions (SIL) in a population of high-risk women in Senegal.Cross-sectional study among 759 female commercial sex workers, including 68 with HIV-1, 58 with HIV-2, 14 with HIV-1 and 2, and 619 without HIV infection.Overall, HPV was detected in 43% of women by polymerase chain reaction (PCR), and in 7% by Southern transfer hybridization, with 7.4% of all women having SIL. The mean CD4 count was 820, 1205, and 727 x 10(6)/l for those with HIV-1, HIV-2, and dual HIV-1 and 2 infections, respectively, and 1447 x 10(6)/l for those without HIV infection. Both HIV-1 and HIV-2 were associated with HPV, as detected by PCR [HIV-1 odds ratio (OR), 2.9; 95% confidence interval (Cl), 1.7-4.9; HIV-2 OR, 1.7; 95% Cl, 1.0-2.9]. HIV-2 was also associated with cervical SIL, and although the association between HIV-1 and SIL did not attain statistical significance, a trend was apparent (HIV-1 OR, 1.8; 95% Cl, 0.7-4.7; HIV-2 OR, 2.9; 95% Cl, 1.2-7.2).Despite less immunosuppression with HIV-2, both HIV-1 and HIV-2 were associated with detection of HPV. HIV-2 was also associated with SIL. Further studies are needed to examine the risks of high-grade SIL and invasive cervical cancer with HIV-1 versus HIV-2 infection.Between February 1990 and March 1993, 759 female commercial sex workers who attended sexually transmitted disease (STD) clinics in Dakar, Thies, and Mbour, Senegal, were interviewed and underwent a general physical and detailed gynecologic examination so researchers could ascertain the influence of HIV-1 and HIV-2 infection on the prevalence of cervical human papillomavirus (HPV) and squamous intraepithelial lesions (SIL) in this high-risk population. Most lesions were low-grade SIL. 619 had neither HIV-1 nor HIV-2 infection. 9%, 8%, and 2% had HIV-1, HIV-2, and concurrent HIV-1 and HIV-2 infection, respectively. Polymerase chain reaction revealed that 43% had HPV infection, while Southern transfer hybridization found only 7%. HIV-1 infected women faced a significant increased risk for HPV (adjusted odds ratio [AOR] = 2.9) as also did HIV-2 infected women (AOR = 1.7). Both these groups also faced an increased risk for SIL (AOR = 1.8 and 2.9, respectively), but the increased risk was not significant. Similarly, women infected with both HIV-1 and HIV-2 faced an increased risk of HPV and SIL (AOR = 4.9 and 5.2, respectively). Among women with HIV infection, women with HPV had a lower CD4 count and CD4/CD8 ratio (854 vs. 1033 million/l, p = 0.08, and 0.88 vs. 1.17, p = 0.05, respectively) than women with no detectable HPV. HIV-positive women with SIL had a lower CD4/CD8 ratio than HIV-positive women without SIL (0.65 vs. 1.03; p = 0.003). HIV-2 women exhibited lower immunosuppression than HIV-1 women. These findings show that both HIV-1 and HIV-2 infection were associated with HPV and SIL. The researchers expressed interest in longitudinal studies designed to examine the risk of high-grade SIL, the direct precursor of invasive cervical cancer, among HIV-infected women.

Background Since 1994, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) has funded research sites in resource-limited countries (RLCs). These sites implement research on human immunodeficiency virus (HIV) infection and Hepatitis C. In parallel, international regulations and recommendations for clinical trials have evolved and proliferated. However, little guidance exists on how these should be interpreted and applied within academic trials and in the context of RLCs. After developing a specific Ethical Charter for research in developing countries in 2002, ANRS developed a set of quality indicators (QIs) as a monitoring tool for assessing compliance to international guidelines. Purpose We describe here the development process, QIs adopted, and areas for improvement. Methods In 2008, a group of experts was convened that included a researcher representing each ANRS site (Cote d’Ivoire, Senegal, Cameroun, Burkina Faso, Egypt, and Cambodia). Our structuring interaction development process combined evidence and expert opinion in two nominal group meetings to identify (1) clinical trial processes involved, (2) issues specific to RLCs in terms of Good Clinical Practice (GCP) and the application of ethical recommendations, and (3) checklists of QIs adapted to clinical trials conducted in RLCs. Results The trial process reviewed and proposed for RLCs was mostly similar to the one produced in wealthier countries. The scheme generated by our work group added two further processes: ‘drug management’ and ‘biological investigations’. Specific issues regarding trial management in RLCs were therefore described for eight trial steps (1) protocol conception and seeking authorizations, (2) participant enrollment and follow-up, (3) site monitoring, (4) drug management, (5) biological investigations, (6) record management, (7) data management, and (8) site closeout. A total of 58 indicators were identified with at least one indicator for each trial process. Limitations Some trial activities require further consideration, that is, in the case of vulnerable participants (children, pregnant women). Proposed indicators are the result of expert consensus and reflect their experience in the HIV field. Relevance to existing trials and extrapolation to other fields must be assessed. Conclusions This innovative program allowed ANRS sites located in RLCs to share their GCP implementation experiences in order to build a list of relevant indicators for clinical trials. The next step is to collect data from ongoing HIV and hepatitis C trials in these settings and will assess the relevance of these indicators to document current quality of performance among trials in resource-limited settings.

Menfegol is a spermicide with in vitro activity against human immunodeficiency virus (HIV). A randomized placebo-controlled safety study covered the use of menfegol foaming tablets for 14 days at increasing frequencies of insertion by 125 prostitutes in Dakar, Senegal. The frequencies of colposcopically diagnosed genital lesions were 5.0%, 11.8%, 27.8%, 49.7%, and 29.4% among menfegol recipients when tablets were used once every other day or 1, 2, 4, or 8 times a day, respectively (P < .05). Among placebo recipients, frequencies were 11.1% and 23.5% when tablets were used < 8 times daily and 8 times daily, respectively. There was no association between subjective genital symptoms and the incidence of colposcopically detected lesions. The high incidence of genital lesions when menfegol foaming tablets were used more than once daily suggests that their frequent use should not be recommended to prevent HIV transmission. In use at low frequency, the tablets' toxicity might be balanced by anti-HIV properties. Safety studies on vaginal microbicides should use objective methods, such as colposcopy, to assess the incidence of lesions.

We assessed trends in the relative prevalences of HIV-1, HIV-2 and dual HIV-1/HIV-2 infection in 10,321 women attending outpatient clinics in Senegal between 1990 and 2009. The relative prevalence of HIV-1 (defined as the proportion of seropositive subjects having HIV-1) rose sharply from 38% in 1990 until 1993 ( P < 0.001), whereupon it continued to rise, but at a slower rate, reaching 72% of HIV infections in 2009. As compared with HIV-1, the relative prevalence of HIV-2 decreased sharply from 54% in 1990 until 1993 ( P < 0.001) and continued to decrease at a slower rate through 2009. The relative prevalence of dual infection, as compared with HIV-1, was stable from 1990 to 1993, but decreased slightly thereafter ( P < 0.001). These study findings indicate that during the early 1990s, the relative prevalence of HIV-1 increased markedly, while the relative prevalence of HIV-2 decreased and the relative prevalence of dual infection remained stable in Senegal. From 1993 to 2009, the relative prevalence of HIV-1 increased at a slower rate, while the relative prevalences of HIV-2 and dual infection decreased. These results confirm trends in HIV prevalence observed in other West African populations and provide a critical update on HIV transmission risk among women in Senegal.

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.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.

The use of didanosine (ddI) in first-line antiretroviral therapy has been recently promoted for resource-limited settings. We therefore compared the long-term effectiveness and safety of the regimen combining ddI, lamivudine, and efavirenz or nevirapine with that of the WHO-recommended regimen of zidovudine (ZDV), lamivudine, and efavirenz or nevirapine in antiretroviral-naïve patients in Senegal.Observational cohort study of patients enrolled between January 2000 and April 2002 in the Senegalese antiretroviral drug access initiative. Multivariate analyses were performed to compare, between the ddI and ZDV groups, the proportion of patients with a viral load500 copies/ml during follow-up; the increase in the CD4 cell count; survival; treatment changes and severe adverse events.Of 151 patients, 71 received the ddI-based treatment and 80 received the ZDV-based treatment. Throughout follow-up, 80-95% of patients had a viral load below 500 copies/ml in both the ddI and ZDV groups (P = 0.5). The CD4 cell count increased after treatment initiation from 176 to 497 cells/mm(3) in the ddI group and from 176 to 567 cells/mm(3) in the ZDV group (P0.3). The rate of death tended to be higher in the ddI group (P = 0.06). ddI was less commonly discontinued than ZDV (P = 0.03).The combination of ddI, lamivudine, and efavirenz or nevirapine resulted in sustained viral suppression and immunological recovery.

To assess the extents and determinants of long-term CD4 cell increases after initiation of antiretroviral therapy (ART), changes in CD4 cell counts were analyzed in a cohort of HIV-1-infected Senegalese using a mixed-effects model. After a median follow-up of 54 months, an average of 483 CD4 cells/mm3 (95% confidence interval [CI] = 331; 680) was reached. The average asymptote level was approximately 421 cells/mm3 (95% CI = 390; 454) in patients with200 cells/mm3 at baseline and approximately 500 cells/mm3 in patients with200 cells/mm3. The independent predictors of long-term CD4 cell reconstitution were the baseline CD4 cell count and the monthly average viral load over the entire follow-up. This good long-term immune reconstitution, optimal in subjects with low average viral loads and200 CD4 cells/mm3 at baseline, argues in favor of the earliest possible access to ART and underlines the importance of strict compliance with the treatment.

Objective: To assess adverse effects of long-term highly active antiretroviral therapy (HAART), that is, lipodystrophy and metabolic disorders, in a cohort of African patients. Methods: One hundred eighty HIV-1-infected patients treated with HAART for 4-9 years in Dakar and 180 age-matched and sex-matched controls were enrolled. Regional subcutaneous fat changes were assessed by physicians, and fasting blood samples were drawn. Centralization of body fat was estimated using skinfold ratio, waist circumference, and waist to hip ratio (WHR). Results: Mean duration of HAART was 5.4 years. Main drugs received were zidovudine, stavudine, and protease inhibitors. The prevalence of moderate-severe lipodystrophy was 31.1% (95% confidence interval: 24.3 to 37.9), with 13.3%, 14.5%, and 3.3% for lipoatrophy, lipohypertrophy, and mixed forms, respectively. Mild-severe lipodystrophy affected 65.0% (58.0; 72.0) of patients. Stavudine was the only independent risk factor (any vs. none: odds ratio = 2.8; 1.4 to 5.5). Patients had lower body mass index and skinfolds but greater centralization of body fat (WHR, P < 0.0001 and skinfold ratio, P < 0.001), fasting glucose (P < 0.0001), homeostasis model assessment insulin resistance, and triglyceride levels (P < 0.01 for both) than controls. Moderately-severely lipodystrophic patients had higher triglyceride and low-density lipoprotein cholesterol than other patients (P < 0.001 and P < 0.05, respectively). Conclusions: Moderate-severe lipodystrophy affected one third of West African patients on long-term HAART and was associated with a less favorable metabolic profile.

Background In 1998, Senegal was among the first sub-Saharan African countries to launch a Highly active anti-retroviral therapy (HAART) access program. Initial studies have demonstrated the feasibility and efficacy of this initiative. Analyses showed a peak of mortality short after starting HAART warranting an investigation of early and late mortality predictors. Methods 404 HIV-1-infected Senegalese adult patients were enrolled and data censored as of September 2005. Predictor effects on mortality were first examined over the whole follow-up period (median 46 months) using a Cox model and Shoenfeld residuals. Then, changes of these effects were examined separately over the early and late treatment periods; i.e., less and more than 6-month follow-up. Results During the early period, baseline body mass index and baseline total lymphocyte count were significant predictors of mortality (Hazard Ratios 0.82 [0.72-0.93] and 0.80 [0.69-0.92] per 200 cell/mm(3), respectively) while baseline viral load was not significantly associated with mortality. During the late period, viro-immunological markers (baseline CD4-cell count and 6-month viral load) had the highest impact. In addition, the viral load at 6-month was a significant predictor (HR = 1.42 [1.20-1.66]). Conclusion In this cohort, impaired clinical status could explain the high early mortality rate while viro-immunological markers were rather predictors of late mortality.

To assess long-term adherence of the first HIV-1 patients receiving highly active antiretroviral therapy (HAART) in Senegal, and to identify the main determinants of adherence.The first 180 patients enrolled in the Senegalese HAART initiative between August 1998 and April 2001 followed up for at least 30 days were eligible. Adherence was assessed monthly at each drug dispensation between November 1999 and November 2006 by a pharmacist using a pill count completed by a questionnaire. Adherence was expressed as the proportion of tablets taken to prescribed tablets. An adherence of 95% was considered to be good. A random-intercept logit model was fitted to identify the main determinants of adherence.Adherence data were available for 158 of 167 eligible patients. Twenty-nine patients died during the study period and 10 were lost to follow-up. Median treatment duration was 78 months, accruing to 6657 person-months of observation. Overall, mean adherence reached 91% [median: 100%, interquartile range (IQR) 96-100%] and adherence exceeded 95% in 78% [95% CI 77-79%] of observations. After 4 years of treatment mean adherence stabilized around 90% and adherenceor =95% stabilized around 70%. Treatment duration and protease inhibitor (PI)-based regimen (indinavir) had a negative effect on adherence, but adherence tended to improve with time for patients receiving a PI. Patient-level variance was highly significant and accounted for a third of total variance.This work demonstrates that good long-term adherence can be achieved in the sub-Saharan context given close monitoring and adherence support measures, confirms the worse adherence for indinavir and underlines the importance of patient heterogeneity.

To investigate the frequency of recombination between HIV-1 and HIV-2 in vivo during dual infection, we performed a retrospective analysis of blood samples from 46 dual HIV-1/HIV-2-seropositive adults for evidence of recombination. HIV viral DNA from peripheral blood mononuclear cells (PBMC) was subjected to two separate nested polymerase chain reaction (PCR) assays using opposing HIV-1 and HIV-2 primer pairs selected to flank a approximately 650-base pair region including the V3 loop of the envelope gene. In the first assay, primers were chosen to amplify recombinants with HIV-1 on the 5' end and HIV-2 on the 3' end, and in the second assay, primers were chosen to amplify recombinants with the opposite orientation. All PCR experiments were run in parallel with positive controls consisting of partial-length env fragments bearing a single central HIV-1/2 recombination site, and appropriate primer-binding sites on each end. The limit of detection for both assays was10 copies of recombinant product per 150,000 cell equivalents of input PBMC DNA. In all 46 dually seropositive patients in this study, PCR screening of PBMC failed to detect evidence of HIV-1/HIV-2 recombinants in the C2-V5 env region. Although genetic recombination between HIV-1 and HIV-2 may occur, we conclude that any such events within env are exceedingly rare, and do not result in the outgrowth of recombinant strains.

Human immunodeficiency virus (HIV) type 2 infection is characterized by slower disease progression to acquired immunodeficiency syndrome than results from HIV-1 infection. To better understand the biological factors underlying the different natural histories of infection with these 2 retroviruses, we examined the relationship between HIV RNA and DNA levels and the rate of CD4(+) T cell decline among 472 HIV-1- and 114 HIV-2-infected individuals from Senegal. The annual rate of CD4(+) T cell decline in the HIV-2 cohort was approximately one-fourth that seen in the HIV-1 cohort. However, when the analysis was adjusted for baseline plasma HIV RNA level, the rates of CD4(+) T cell decline per year for the HIV-1 and HIV-2 cohorts were similar (a rate increase of approximately 4% per year for each increase in viral load of 1 log(10) copies/mL). Therefore, plasma HIV load is predictive of the rate of CD4(+) T cell decline over time, and the correlation between viral load and the rate of decline appears to be similar among all HIV-infected individuals, regardless of whether they harbor HIV-1 or HIV-2.

OBJECTIVES To assess temporary expatriation as a risk factor for HIV infection in a rural area of Senegal and to examine the transmission of HIV from expatriates to their families. DESIGN Cross-sectional study in identified expatriates and in a representative cluster sample of the general population from the same geographical area in northern Senegal. METHODS In 1989, a survey (including questionnaire and serological tests for HIV-1 and HIV-2) was conducted in all expatriates currently living in 11 villages in northern Senegal and spouses of all expatriates (present or not) from this area ('expatriate' group, n = 258). In parallel, a cluster sample of 600 adults was drawn from eight villages of the same area, of whom 414 were selected as the control group since they and their spouses had not travelled outside Senegal in the last 10 years. RESULTS In the 'expatriate' group, sera from 39 subjects were confirmed as HIV-positive by Western blot [17 out of 63 men (27.0%) and 22 out of 195 women (11.3%)]. Of these subjects, 33 were infected by HIV-1, four by HIV-2 and two had a dual HIV-1/2 profile. In contrast, only two subjects (one man and one woman) from the control group were infected by HIV-2 and none by HIV-1. In men, HIV-1 seroprevalence was associated with age < 40 years [odds ratio (OR), 7.4; P = 0.03] and previous sexually transmitted disease (STD) symptoms (OR, 13.5; P = 0.03), whereas the risk factors in women were age < 25 years (OR, 3.7; P = 0.04), being a widow (OR, 30.4; P < 0.01) and presence of sexual activity over the last 2 years (OR, 21.3; P < 0.01). CONCLUSIONS Penetration of HIV-1 infection in a country where HIV-2 is endemic shows that the HIV-1 epidemic is currently spreading to rural West Africa. Migrant workers appear to play a major role in this epidemic.

The authors studied the prevalence and risk determinants for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in female prostitutes from Dakar (1985-1990), Ziguinchor (1987-1990), and Kaolack (1987-1990), Senegal, West Africa. Each cohort showed a distinct distribution of HIVs: 10.0% HIV-2 and 4.1% HIV-1 in Dakar, 38.1% HIV-2 and 0.4% HIV-1 in Ziguinchor, and 27.4% HIV-2 and 1.3% HIV-1 in Kaolack. In 1,275 female prostitutes from Dakar, increase years of sexual activity and a history of scarification were associated with HIV-2 seropositivity. In contrast, HIV-1 seroprevalence was associated with a shorter duration of prostitution and a history of hospitalization. In 278 female prostitutes from Ziguinchor, HIV-2 seroprevalence was associated with women of Guinea-Bissau nationality and increased years of sexual activity. In 157 female prostitutes from Kaolack, HIV-2 seroprevalence was associated with increased years of sexual activity and a history of never using condoms. The authors also studied the risk determinants for HIV-2 in the 1,280 Senegalese prostitutes pooled from all three sites. Controlling for ethnic group, women from Ziguinchor and Kaolack were more likely to be HIV-2 seropositive as compared with women from the Dakar site. Increased years of sexual activity were associated with HIV-2 seropositivity, while a history of excision and BCG vaccinations decreased the risk of HIV-2 infection.

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.

We studied the clinical status and certain hematologic and immunologic parameters in healthy prostitutes from Dakar, Senegal who were seropositive for antibodies to human immunodeficiency virus type-2 (HIV-2). Generalized lymphadenopathy and clinical signs or symptoms similar to those which are seen with human immunodeficiency virus type-1 (HIV-1) infection were not present. Comparison to seronegative prostitutes and minor surgery control patients were made and significant elevations were seen in T8 lymphocytes (p = .03), IgG (p = .0001), and beta 2-microglobulin (p = .03). The mean T4 lymphocyte count in seropositive prostitutes was lower than in seronegative prostitutes (757 vs. 1179, p = .15), but this difference was not statistically significant and appeared to be correlated with age. No significant differences were noted between the seronegative and seropositive prostitutes in lymphocyte stimulation studies to certain mitogens. Antilymphocyte antibodies above background were not present in either population. We conclude that HIV-2 is a sexually transmitted agent that produces immunologic alterations consistent with a persistent viral infection. HIV-2 seropositive prostitutes studied to date do not show clinical signs of immune suppression, as has been described with HIV-1 infection. The pathogenic potential of HIV-2 appears to differ from that of HIV-1, the etiologic agent of the AIDS pandemic.

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International audience