Ibra Ndoye

Equal Plasma Viral Loads Predict a Similar Rate of CD4± T Cell Decline in Human Immunodeficiency Virus (HIV) Type 1- and HIV-2-Infected Individuals from Senegal, West Africa

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.

HIV-1, HIV-2, human papillomavirus infection and cervical neoplasia in high-risk African women

ObjectiveTo 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. Design and participantsCross-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. ResultsOverall, 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 727×106/l for those with HIV-1, HIV-2, and dual HIV-1 and 2 infections, respectively, and 1447×106/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 (CD, 1.7–4.9; HIV-2 OR, 1.7; 95% CI, 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% CI, 0.7–4.7; HIV-2 OR, 2.9; 95% CI, 1.2–7.2). ConclusionsDespite 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.

Sequence Note: Identification of All HIV Type 1 Group M Subtypes in Senegal, a Country with Low and Stable Seroprevalence

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.

Temporary expatriation is related to HIV-1 infection in rural Senegal.

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.

Lipodystrophy and metabolic disorders in HIV-1-infected adults on 4- to 9-year antiretroviral therapy in Senegal: a case-control study.

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.

Primary prevention with cotrimoxazole for HIV-1-infected adults : Results of the pilot study in Dakar, Senegal

Objectives: To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV‐1‐infected adults. Design: Randomized, double‐blind, placebo‐controlled clinical trial in the urban community of Dakar, Senegal. Methods: Eligibility criteria were age greater than 15 years, HIV‐1 or HIV‐1 and HIV‐2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, 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. Results: 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: 0.55‐2.59). 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). Conclusion: Our 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.

A 84-month follow up of adherence to HAART in a cohort of adult Senegalese patients

Objectives  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.

Molecular Epidemiology of Dual HIV-1/HIV-2 Seropositive Adults from Senegal, West Africa

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.

Accuracy of two enzyme immunoassays and cell culture in the detection of Chlamydia trachomatis in low and high risk populations in Senegal.

Two enzyme immunoassays (EIAs), Chlamydiazyme (CZ; Abbott Laboratories) and Pathfinder (PF; Kallestadt), were compared with a cell culture technique in the detection of cervicalChlamydia trachomatis infection in 670 women in urban settings in Senegal (377 pregnant women and 293 prostitutes). Positive CZ and positive PF specimens were tested a second time using a monoclonal antibody blocking technique. True positive specimens were defined as those positive on culture or positive on EIA with confirmation of the result after blocking. Using this definition, the prevalence of genital chlamydial infection was 14.6 % and 14.3 % in pregnant women and prostitutes respectively. An important difference between the two populations was that the pregnant women were younger than the prostitutes, which might explain the fact that the prevalence of infection among the pregnant women was as high as that among the prostitutes, although the age-adjusted prevalence was higher among prostitutes than among pregnant women. The chlamydial detection rates of cell culture, CZ and PF were 62 % (26/42), 69 % (29/42) and 86 % (36/42) respectively in prostitutes and 76 % (42/55), 40 % (22/55) and 53 % (29/55) respectively in pregnant women. Agreement between the tests was 89 %, 85 % and 88 % for culture/CZ, culture/PF and CZ/PF respectively. However, when data were adjusted for chance agreement, kappa coefficients were 0.40 for culture/CZ, 0.34 for culture/PF and 0.48 for CZ/PF. These results indicate that the accuracy of the EIAs and cell culture may vary greatly in different populations: both EIAs showed a distinctly higher detection rate than culture in prostitutes and a significantly lower detection rate in pregnant women. Confirmation of positive EIA results with a blocking assay greatly enhanced the specificity of the antigen detection tests and should be obtained when using the EIAs in a clinical setting.

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.