Ibrahima Ndoye

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.

The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study.

ObjectiveTo study the feasibility, effectiveness, adherence, toxicity and viral resistance in an African government HAART initiative. MethodsA prospective observational cohort study started in Dakar in August 1998. Initial treatment consisted of two nucleoside reverse transcriptase inhibitors and one protease inhibitor. The patients attended monthly medical examinations. Plasma HIV-1 RNA and CD4 cell counts were determined at baseline and every 6 months. Intention-to-treat analyses were performed. ResultsFifty-eight treatment-naive patients, mostly infected by HIV-1 strain CRF02-AG, were enrolled. Most were at an advanced stage of HIV disease (86.2% had AIDS). Adherence was good in 87.9% of patients and treatment was effective in most of them. Thus, HIV-1 RNA was undetectable in 79.6, 71.2, 51.4 and 59.3% of patients at months 1, 6, 12 and 18, respectively and the median viral load reduction was ∼2.5 log10 copies/ml. The CD4 cell count rose by a median of 82, 147 and 180 × 106 cells/l at months 6, 12 and 18, respectively. At the same time points, the cumulative probability of remaining alive or free of new AIDS-defining events was 94.8, 85.0 and 82.3%. Most adverse effects (80.8%) were mild or moderate and only two cases of drug resistance occurred. ConclusionThis study shows that HAART is feasible and well tolerated in African patients. Clinical and biological results were comparable to those seen in western cohorts, despite differences in the HIV-1 subtype distribution and an advanced disease stage when the treatment was initiated. Contrary to other recent studies in Africa, viral resistance rarely emerged.

HIV infection and sexually transmitted infections among men who have sex with men in Senegal

Background:No epidemiological study has been conducted on HIV and vulnerability to sexually transmitted diseases (STI) among men who have sex with men (MSM) in sub-Saharan Africa Method:A survey including questionnaire, physical examination and detection of HIV and STI was carried out among 463 MSM, aged 18–52 years, recruited through the snowball technique in five urban sites throughout Senegal. Results:A total of 21.5% of men were found to be infected with HIV [95% confidence interval (CI), 17.8–25.6]. Active syphilis, positive serology for herpes simplex virus (HSV)-2, and polymerase chain reaction detection in urine of Chlamydia and gonorrhea infections were recorded in 4.8, 22.3, 4.1 and 5.4% of participants, respectively. Most respondents reported sex with women (94.1%). In the month preceding the interview, 24% reported at least one unprotected insertive anal intercourse with a male partner, 20% at least one unprotected receptive anal intercourse, and 18% at least one unprotected intercourse with a female partner. Genital examination showed that 5% of participants had at least one clinical sign of STI. Factors associated with HIV infection were age group, the reporting of more than nine lifetime male partners [odds ratio (OR), 3.76; 95% CI, 1.61–8.79], being a waiter or bartender (OR, 3.33; 95% CI, 1.41–7.84), and living in Dakar (OR, 3.33; 95% CI, 1.07–3.43). Conclusion:Men who have sex with men in Senegal are highly infected with HIV and other STI. Intervention programs targeting this population are urgently needed, given their particular vulnerability and because infections are likely to disseminate into the general population given the high proportion of bisexual activity in this community.

Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults.

Objectives: To assess the long-term survival, as well as the immunologic and virologic effectiveness, adherence, and drug resistance, in HIV-infected patients receiving highly active antiretroviral therapy (HAART) in one of the oldest and best-documented African cohorts. Methods: A prospective observational cohort study included the first 176 HIV-1-infected adults followed in the Senegalese government-sponsored antiretroviral therapy initiative launched in August 1998. Patients were followed for a median of 30 months (interquartile range, 21-36 months). HAART comprised 2 nucleoside reverse transcriptase inhibitors and either 1 protease inhibitor or 1 nonnucleoside reverse transcriptase inhibitor. Results: At baseline, 92% of patients were antiretroviral naive and 82% had AIDS; the median CD4 count was 144 cells/mm3, and median viral load was 202,368 copies/mL. The survival probability was high (0.81 at 3 years; 95% CI, 0.74-0.86) and was independently related to a baseline hemoglobin level <10 g/dL and a Karnofsky score <90%. Antiviral efficacy was consistently observed during the 3 years of treatment (−2.5 to −3.0 log10 copies/mL; 60-80% of patients with viral load <500 copies/mL) and the CD4 count increase reached a median of 225 cells/mm3. Most patients reported good adherence (80-90%). The emergence of drug resistance was relatively rare (12.5%). Conclusion: This study shows that clinical and biologic results similar to those seen in Western countries can be achieved and sustained during the long term in Africa.

Concurrent sexual partnerships and HIV prevalence in five urban communities of sub-Saharan Africa.

ObjectiveTo estimate parameters of concurrent sexual partnerships in five urban populations in sub-Saharan Africa and to assess their association with levels of HIV infection and other sexually transmitted infections (STI). MethodsData were obtained from a multicentre study of factors which determine the differences in rate of spread of HIV in five African cities. Consenting participants were interviewed on sexual behaviour and at four of the five sites also provided a blood and a urine sample for testing for HIV and other STI. Data on sexual behaviour included the number of partnerships in the 12 months preceding the interview as well as the dates of the start and end of each partnership. Summary indices of concurrent sexual partnerships – some of which were taken from the literature, while others were newly developed – were computed for each city and compared to HIV and STI prevalence rates. ResultsA total of 1819 adults aged 15–49 years were interviewed in Dakar (Senegal), 2116 in Cotonou (Benin), 2089 in Yaoundé (Cameroon), 1889 in Kisumu (Kenya) and 1730 in Ndola (Zambia). Prevalence rates of HIV infection were 3.4% for Cotonou, 5.9% for Yaoundé, 25.9% for Kisumu and 28.4% for Ndola, and around 1% for Dakar. The estimated fraction of sexual partnerships that were concurrent at the time of interview (index k) was relatively high in Yaoundé (0.98), intermediate in Kisumu (0.44) and Cotonou (0.33) and low in Ndola (0.26) and in Dakar (0.18). An individual indicator of concurrency (iic) was developed which depends neither on the number of partners nor on the length of the partnerships and estimates the individual propensity to keep (positive values) or to dissolve (negative values) on-going partnership before engaging in another one. This measure iic did not discriminate between cities with high HIV infection levels and cities with low HIV infection levels. In addition, iic did not differ significantly between HIV-infected and uninfected people in the four cities where data on HIV status were collected. ConclusionWe could not find evidence that concurrent sexual partnerships were a major determinant of the rate of spread of HIV in five cities in sub-Saharan Africa. HIV epidemics are the result of many factors, behavioural as well as biological, of which concurrent sexual partnerships are only one.

HIV prevalence, previous HIV testing, and condom use with clients and regular partners among Senegalese commercial sex workers

Objectives: To assess HIV prevalence and risk factors for HIV infection, to investigate condom use among registered female commercial sex workers (CSWs) in Senegal, West Africa, and to examine the association between previous HIV testing, knowledge of HIV serostatus and condom use with both regular sex partners and clients within this population. Methods: A cross-sectional study was conducted at three sexually transmitted disease clinics among 1052 Senegalese registered CSWs between 2000 and 2004. Inperson interviews soliciting information concerning demographic characteristics, medical history, sexual behaviour with clients and regular partners, and previous HIV testing history were performed. Blood samples were collected for determination of HIV-1 and/or HIV-2 serostatus. Multivariable, Poisson and log-binomial models were used to calculate prevalence ratios. Results: The overall HIV prevalence was 19.8%. Over 95% of CSWs reported always using a condom with clients, but only 18% reported always using a condom with their regular partners. A history of previous HIV testing was not associated with condom use with clients (adjusted prevalence ratio (APR) = 0.98, 95% confidence intervals, CI: 0.90 to 1.06). However, prior HIV testing was associated with decreased condom use with their regular partners (APR = 0.44, 95% CI: 0.28 to 0.69), especially in women who tested HIV negative (APR = 0.17, 95% CI: 0.08 to 0.36). Conclusions: CSWs in Senegal have a high HIV prevalence; therefore preventing HIV transmission from this population to the general population is important. Condom use with regular partners is low among registered CSWs in Senegal, and a prior HIV negative test is associated with even less condom use with regular partners. Intervention efforts to increase condom use with regular sexual partners are needed.

Religion and protective behaviours towards AIDS in rural Senegal.

ObjectivesTo describe the association between religion and factors related to sexually transmitted diseases (STD)/AIDS in a country where religious leaders were involved early in prevention. DesignA cross-sectional study conducted in a rural area in central Senegal. MethodsQuestionnaire-based interviews of a random sample of 858 adults from the general population aged 15–59 years and in-depth interviews of four religious leaders and 50 people. ResultsSeventy-six per cent of the respondents were Muslim, 24% Catholic, 1% Animist and 0.2% Protestant. A total of 86% of men and 87% of women reported religion to be very important to them. Important prevention-related variables were inversely associated with the importance of religion. Men who considered religion to be very important were less likely to cite AIDS as a major health problem [odds ratio (OR) 0.4, P = 0.008] and were less likely to feel at risk of getting HIV (OR 0.5, P = 0.0005). Women who considered religion to be very important were less likely to report an intention to change to protect themselves from AIDS (OR 0.2, P = 0.0001), less likely to report having discussed AIDS with others (OR 0.4, P = 0.01) and much more likely to feel at risk of getting HIV (OR 9.3, P = 10−4). Individuals who considered religion to be very important were not more likely to report intending to or actually having become faithful to protect themselves from AIDS. ConclusionThese findings stress the need to intensify the involvement of religious authorities in HIV/STD prevention at the local level.

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 (P value = 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.

Low rate of genotypic HIV-1 drug-resistant strains in the Senegalese government initiative of access to antiretroviral therapy.

ObjectiveTo monitor the prevalence of antiretroviral (ARV)-resistant HIV-1 viruses, and the genotypic mutations in patients enrolled in the Senegalese initiative for access to antiretroviral treatment (ART). MethodsA total of 80 patients with a virological follow-up of at least 6 months were selected, 68 were ART-naive and 12 ART-experienced. Genotypic resistance to ARV was studied at baseline for a random subset of patients and at each rebound in plasma viral load during ART, by sequencing the protease and reverse transcriptase genes. ResultsAt baseline, 66 patients received highly active antiretroviral therapy (HAART) [2 nucleoside reverse transcriptase inhibitors (NRTIs) +1 protease inhibitor (PI) (n = 64) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (n = 2)] and 14 patients (17.5%) started with a dual therapy because of ongoing anti-tubercular therapy or efficient previous bitherapy for the ART-experienced patients. The emergence of drug-resistant viruses (n = 13) during follow-up was more frequent in ART-experienced patients than in ART-naive patients, 41.7 versus 11.8%, resistant viruses emerged at comparable follow-up periods, a median of 17.8 and 18.3 months, respectively. In patients receiving zidovudine and lamivudine in their drug regimen, resistance to lamivudine was more frequent than to zidovudine. Two of the three patients, with viruses resistant to PIs, acquired mutations associated with cross-resistance. Strikingly, five (39%) of the 13 patients developed resistances to drugs that they had never received (n = 3) or that they received 18 or 36 months ago (n = 2). Didanosine/stavudine pressure had selected zidovudine-resistant viruses in four patients, and indinavir had selected a nelfinavir-resistant virus in one patient. ConclusionIn contrast to other reports from developing countries where patients had received ARVs in an uncontrolled manner, our study showed that implementation of HAART together with good clinical, biological and logistical monitoring can reduce the emergence of resistant strains in Africa.

Access to antiretroviral drugs and Aids management in Senegal

ObjectivesDescription and analysis of the Senegalese Antiretroviral Drug Access Initiative (ISAARV), the first governmental highly active antiretroviral therapy (HAART) treatment programme in Africa, launched in 1998. Methods and resultsISAARV was initially an experimental project designed to evaluate the feasibility, efficacy and acceptability of HAART in an African context. It was based on four principles: collective definition of the strategy, with involvement of the health professionals who would be called on to execute the programme; matching the objectives to available means (gradual enrollment according to drug availability); monitoring by several research programmes; and ongoing adaptation of treatment and follow-up according to the latest international recommendations.Persons qualifying for antiretroviral (ARV) therapy are selected on the basis of immunological and clinical criteria, regardless of economic and social considerations. A system of subsidies was created to favor access to ARV. Following the ARV price reductions that occurred in November 2000, 100% subsidies were created for the poorest participants. Optimal adherence was ensured by monthly follow-up by pharmacists and support groups held by social workers and patient associations. The chosen supply and distribution system allowed drug dispensing to be strictly controlled. ConclusionThe ISAARV programme demonstrates that HAART can be successfully prescribed in Africa. This experience has served as the basis for the creation of a national treatment programme in Senegal planned to treat 7000 patients by 2006.