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Background: Although 90% of HIV-1-infected children live in sub-Saharan Africa, morbidity data after highly active antiretroviral therapy (HAART) initiation in these settings are limited. The objective of this study was to document the incidence of AIDS-defining events and non-AIDS-defining diseases in African children receiving HAART., Methods: Incidences rates (IRs) of AIDS-defining events and 10 other common diseases were estimated overall and by current CD4-strata (<15%, 15 - <25% and ≥25%) from 2 prospective cohorts of African children., Results: One hundred eighty-eight children contributing to 355 children-years were included. The documented morbidity IRs per 100 children-years were upper respiratory infections, 100 (87-114); infectious diarrhea, 37 (31-44); World Health Organization (WHO) stage 2 events, 22.9 (18.2-28.1); and WHO stage 3/4 events, 12.3 (9.1-16.7). IRs of WHO stage 2 events, severe bacterial infections, infectious diarrhea and pneumonia decreased linearly across all CD4%-strata, whereas WHO stage 3/4 events and viral infections occurred mostly when CD4% <15%. Overall, IRs decreased during the first 2 years on HAART except for upper respiratory infection, mycosis and oral candidiasis., Conclusion: This incidence of AIDS- and non-AIDS-defining diseases declined substantially after HAART in 2 African cohorts, although estimates remained high compared with high-resource settings. Without renewed efforts to increase antiretroviral scale-up, children in developing countries will continue to have a high burden of infections.

Background: CD4-specific rates of mortality in sub-Saharan African adults with high CD4 counts have rarely been estimated. This estimation is useful to the when to start antiretroviral treatment (ART) debate., Methods: We pooled data from National Agency for Research on AIDS and Viral Hepatitis (ANRS)-funded research cohorts or associated partners in West Africa. All HIV-infected adults (≥18 years) with available follow-up time off ART were eligible. We used a joint model to estimate CD4 count evolution. We estimated CD4-specific rates of mortality, loss-to-follow-up (LTFU) and ART initiation by dividing the number of first event by the follow-up time off ART within each CD4 category., Results: Between 1996 and 2009, 2588 adults (80% women) from 5 cohorts in Cote d'Ivoire and Burkina Faso were followed off ART during 6862 person-years. In the 201-350, 351-500, 501-650, and >650 cells per cubic millimeter CD4 categories, mortality rates were: 3.0, 1.5, 0.4, 0.2 per 100 person-years; LTFU rates: 6.0, 4.6, 6.1, 6.0 per 100 person-years; and ART initiation rates: 18.1, 2.7, 0.5, 0.5 per 100 person-years, respectively. All estimates varied across cohorts; mortality rates were higher when rates of LFTU and ART initiation were lower; LTFU rates were 2-40 times higher than mortality rates., Conclusions: Among untreated West African adults with high CD4 counts, mortality and LTFU rates were substantial. Even when data are collected under research conditions, informative censoring due to ART initiation and LTFU could lead to significantly underestimate mortality figures.

Objectives: To evaluate the frequency and progression over time of the WHO-defined transmitted HIV-1 drug resistance mutations (DRMs) among antiretroviral treatment (ART)-naive HIV-1-infected patients in Cameroon., Design: We analyzed HIV-1 DRM data generated from 369 ART-naive individuals consecutively recruited between 1996 and 2007 in urban and rural areas in Cameroon., Methods: HIV-1 drug resistance genotyping was performed in the pol gene using plasma samples and surveillance DRMs were identified using the 2009 WHO-DRM list., Results: We observed in Yaounde, the capital city, an increasing prevalence of DRMs over time: 0.0% (none of 61 participants) in 1996-1999; 1.9% (one of 53 participants) in 2001; 4.1% (two of 49 participants) in 2002; and 12.3% (10 of 81 participants) in 2007. In the rural areas with more recently implemented ART programs, we found DRMs in six of 125 (4.8%) ART-naive individuals recruited in 2006-2007. DRMs identified in both areas included resistance mutations to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) that might impair the efficacy of available first-line and second-line treatments., Conclusion: This report showed an increase in transmitted DRMs in areas where antiretroviral drugs were introduced earlier, although other factors such as natural viral polymorphisms and acquired DRMs through exposure to antiretroviral cannot be totally excluded. Further surveillances are needed to confirm this evolution and inform public health policies on adequate actions to help limit the selection and transmission of drug-resistant HIV, while scaling up access to ART in developing countries.

Objectives: Antiretroviral treatment (ART) scale-up in sub-Saharan Africa has made it possible to investigate the maintenance of adherence to HIV medications. We describe here adherence to ART and identify its correlates in the Cameroonian context., Design: Prospective cohort study in 9 rural district hospitals., Methods: A mixed logistic regression model was used to identify factors associated with adherence to ART in 401 patients with data prospectively collected on adherence., Results: Although 73% of patients were adherent after the first month on ART, this proportion decreased to 61% after 24 months. After adjustment for known factors of adherence to ART (such as knowledge, motivation and side-effects), patients who reported willingness to start ART before initiation, those who were satisfied with information provided by their physicians, and those who implemented reminder methods for ART intake {eg, using an alarm clock, mobile phone, or watch [odds ratio (95% confidence interval)] = 2.45 (1.58 to 3.79), but also the help of a relative to remind them or other methods} were more likely to be adherent to ART., Conclusions: Besides highlighting some correlates already known to have an impact on adherence to ART, our findings also underline the need to reinforce the counseling component of follow-up through innovative methods. Accordingly, training and implementation research should encourage the use of medication reminder methods, such as mobile phones, to assure adherence over time and improve long-term response to ART.

Objectives: To compare adherence to antiretroviral therapy using drug level monitoring and self-report and to explore the relation between these 2 methods and viral load measurements., Methods: Sixty patients received a fixed-dose combination of nevirapine, stavudine, and lamivudine in a clinical study in Cameroon. Adherence was assessed every 6 months until month 36 by nevirapine minimal plasma concentration and self-report. Plasma HIV-1 viral load was determined at the same time. Analyses included 159 complete observations., Results: The proportion of patients labeled as "adherent" was significantly lower using nevirapine monitoring (88.7%, 95% confidence interval [CI]: 82.7 to 93.2) than self-report (97.5%, CI: 93.7 to 99.3; P = 0.002). Virologic failure was associated with the nevirapine concentration (adjusted odds ratio [aOR] = 4.43; P = 0.018) but not with the self-reported adherence (aOR = 0.84; P = 0.9). As compared with the virologic outcome, the sensitivity of nevirapine level monitoring for predicting inadequate adherence was 20.5%, the specificity was 91.7%, the positive predictive value was 44.4%, and the negative predictive value was 78.0%. For self-report, the respective values were 2.6%, 97.5%, 25.0%, and 75.5%., Conclusions: Drug level monitoring provided a more reliable estimate of adherence than self-report. This method could be used in research settings. Operational research is required to define how to improve the accuracy of the self-report method because it is the most feasible method in clinical practice.

Background: Western randomized trials and prospective cohorts in resource-limited settings have proven virological success with stavudine-based highly active antiretroviral therapy. However, stavudine is no longer recommended in first-line treatments in these two settings due to its intrinsic toxicities and side effects. Yet it remains a cornerstone of treatment in resource-limited settings, due to lack of alternatives and its availability in generic fixed-dose combinations., Objective: To review the toxic effects of stavudine and their prevention and management strategies, especially in resource-limited settings., Methods: Data from clinical and pharmacological trials in Western countries, as well as prospective cohorts in resource-limited settings, were reviewed., Conclusion: Initiating or switching to less toxic nucleoside analogues whenever possible, or lowering stavudine doses to 30 mg b.i.d., is strongly recommended.

We compared the tolerability and effectiveness of two major first-line regimens used in resource-limited settings, namely zidovudine-lamivudine-nevirapine and stavudine-lamivudine-nevirapine. HIV-1-infected adults in Cameroon were enrolled in a prospective cohort study between 2001 and 2003. They were eligible if they had AIDS or a CD4 cell count below 350/mm(3), a Karnofsky score over 50%, and no contraindications to antiretroviral treatment. The patients were followed up to 2 years. Of 169 patients, 85 received zidovudine-lamivudine-nevirapine and 84 stavudine-lamivudine-nevirapine. The incidence rates of treatment changes, death, drug resistance, and severe adverse effects were, respectively, 12.0 [95% confidence interval (CI) 7.2-19.9] and 10.9 (CI 6.4-18.3) per 100 person-years; 5.7 (CI 2.8-11.4) and 7.6 (CI 4.2-13.7); 2.9 (CI 1.1-7.7) and 5.0 (CI 2.4-10.6); and 41.7 (CI 30.2-57.6) and 49.1 (CI 36.1-66.6). The Kaplan-Meier curves for the likelihood of remaining on the initial regimen (p = 0.8) and for survival (p = 0.5) did not differ significantly between the groups. In Cox multivariate analysis only a lower baseline CD4 cell count was associated with death (p < 0.001). The proportion of patients with undetectable viral load and the increase in the CD4 cell count were similar in the two groups. Anemia was rare (4% vs. 6%). Five cases of severe peripheral neuropathy and one case of lipodystrophy occurred. This study suggests that the zidovudine-lamivudine-nevirapine combination is a safe first-line treatment, even in settings with few laboratory resources. In view of stavudine toxicity, these results support recommendations calling for a gradual switch from stavudine- to zidovudine-based regimens.

Aims: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART., Methods: The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration., Results: Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation., Conclusions: Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

We assessed the long-term safety, effectiveness and quality of a fixed-dose combination of nevirapine, stavudine and lamivudine (triomune). HIV-1-infected adults initially enrolled in a one-year, open-label, single-arm, multicentre trial in Cameroon were followed for 2 years. Our results support the safety and effectiveness of the triomune combination for first-line treatment of HIV infection. Virological effectiveness appeared to wane somewhat during the second year of treatment, however, and plasma nevirapine concentrations were relatively high.

Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.5% had resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 10.2% to non-NRTIs, and 2.3% to protease inhibitors.

Objectives: To evaluate survival and investigate causes of death among HIV-1 infected adults receiving HAART in Senegal., Design: An observational prospective cohort., Methods: Mortality was assessed in the first patients enrolled between August 1998 and April 2002 in the Senegalese antiretroviral drug access initiative. First-line regimen combined two nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. The most likely causes of death were ascertained through medical records or post-mortem interviews (verbal autopsy)., Results: Four hundred and four patients (54.7% women) were enrolled in the study and were followed for a median of 46 months (interquartile range: 32-57 months) after HAART initiation. At baseline, 5% were antiretroviral therapy (ART) non-naive, 39 and 55% were respectively at CDC stage B and C, median age, CD4 cell count and viral load were 37 years, 128 cells/microl and 5.2 log cp/ml, respectively. Ninety-three patients died during follow-up and the overall incidence rate of death was 6.3/100 person-years [95% confidence interval (CI), 5.2-7.7]. During the first year after HAART initiation, 47 patients died and seven were lost to follow-up, yielding to a probability of dying of 11.7% (95% CI, 8.9-15.3%). The death rate, which was highest during the first year after HAART initiation, decreased with time yielding a cumulative probability of dying of 17.4% (95% CI, 13.9-21.5%) and 24.6% (95% CI, 20.4-29.4%) at 2 and 5 years. Causes of death were ascertained in 76 deaths. Mycobacterial infections, neurotropic infections and septicaemia were the most frequent likely causes of death., Conclusions: This study underlines the early mortality pattern after HAART initiation and highlights the leading role of mycobacterial infections in the causes of death.

Background: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings., Methods: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naïve adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses., Findings: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61)., Interpretation: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Although it is now well established that a substantial proportion of wild-living primates in sub-Saharan Africa harbor SIV, no study to date has examined to what extent the various species are naturally infected. In this study, we first describe the development and validation of sensitive and specific SIV antibody detection assays representing all major known primate lentiviral lineages on a panel of 207 sera from 11 different primate species with known infection status. The newly developed assays were then used to determine SIV prevalence rates in nine primate species native to Cameroon. Analysis of 722 sera revealed widely varying prevalence rates, ranging from an apparent absence of SIV infection in crested mona (0/70), grey cheeked (0/36) and agile mangabeys (0/92), to prevalence rates of 3%, 4%, 11%, 27%, 39% and 52% for mustached (6/203), greater spot-nosed (8/193), northern talapoin (3/26), mantled guereza (14/52), De Brazza's (9/23) and mandrill (14/27) monkeys, respectively. The epidemiology of naturally occurring SIV infections is thus more complex than previously appreciated and the various non-human primate hosts seem to differ in their susceptibility to SIV infection. The newly developed assays should now permit to define with greater accuracy existing SIV reservoirs and associated human zoonotic risk.

We analysed whether mutations associated with resistance to antiretroviral (ARV) drugs circulate among treatment-naive HIV-1-infected individuals at a period when these drugs started to become more widely available in Africa. Overall, major resistance mutations in the pol gene, as defined by the International AIDS Society Resistance Testing-USA panel, were observed in 16 treatment-naive individuals. Eight of the 97 patients tested in Burkina Faso bore mutations conferring resistance to one drug class of ARV drugs: two to nucleoside reverse transcriptase inhibitors (NRTIs; M41L [n = 1], M41L+T69S [n = 1]), four to non-NRTIs (NNRTIs; V106A/V [n = 1] and V1081 [n = 3]) and two to protease inhibitors (PIs; L33F [n = 2]). In Cameroon, resistance mutations were identified in 8 of 102 patients: three to PIs (M461/L [n = 2], L33F [n = 1]), three to NRTIs (T69N/T [n = 1], M184V [n = 1], A62V [n = 1]) and two to NNRTIs (P236L [n = 1], V1081 [n = 1]). It is important to note that not all genotypic drug-resistance algorithms give similar interpretations to the observed mutations. Population surveillance for ARV drug resistance is required and should be included in all implementation programmes.

The Democratic Republic of Congo (DRC) is characterized by low and stable HIV prevalences and high HIV-1 genetic diversity and is most probably the epicenter of HIV-1 group M. Our major goal was to study the distribution of HIV-1 variants over a 5-year period against a background of political instability and civil war. A total of 288 HIV-1-positive samples collected in 2002 from sentinel population groups in an HIV serosurveillance study performed in 4 cities (Kinshasa [capital city], Mbuji-Mayi [south], Lubumbashi [southeast], and Kisangani [northeast]) were genetically characterized by sequencing and phylogenetic analysis of the V3-V5 env region. The results were compared with those obtained in 1997. Similarly, as in 1997, an extremely high genetic diversity of HIV-1 strains overall and a heterogeneous geographic distribution were seen in 2002. All subtypes and several circulating recombinant forms were present, high intrasubtype diversity was observed, and 5.6% of the samples could not be classified. In each geographic region of the DRC, the genetic diversity was significantly higher than in neighboring countries. Comparison of subtype distribution in similar population groups in Kinshasa in 1997 and 2002 revealed an overall increase of subtype C in Kinshasa from 2.1% to 9.7% and, more precisely, from 0% to 18.9% in female sex workers (P = 0.013). Genetic characterization of HIV-positive samples from sentinel surveys adds significant additional information on new trends in the HIV epidemic. These changes could have implications regarding the spread of HIV infection in the DRC as well on vaccine and/or treatment strategies.

A review of the hospital charts for 788 patients treated in 19 public and private clinics in Cameroon showed that clinical follow-up visits, biologic follow-up visits, and drug supply were irregular and that many patients interrupted treatment. Virological and immunologic effectiveness of therapy was as expected in patients for whom results were available.

Objective: To assess the effectiveness of generic anti-retroviral drugs in terms of survival and virological and immunological responses, as well as their tolerability and the emergence of viral resistance., Methods: A total of 109 HIV-1-infected patients were enrolled in a prospective cohort study in Yaoundé, Cameroon. Available generic drugs were a fixed-dose combination (FDC) of zidovudine (ZDV) and lamivudine (3TC), an FDC of 3TC, stavudine (d4T) and nevirapine (NVP), and individual formulations of ZDV, 3TC and NVP., Results: At baseline, the median CD4 cell count was 150/mm3 [interquartile range (IQR) 61-223] and median viral load was 5.4 log10 copies/ml (IQR 4.8-5.6); 78% of patients received ZDV/3TC/NVP and 22% received 3TC/d4T/NVP. Median follow-up was 16 months (IQR 11-23). The survival probability was high (0.92 at 12 months); plasma viral load declined by a median of 3.3 log10 copies/ml and 86.9% of the intention-to-treat population had viral load <400 copies/ml at 12 months; CD4 count had increased by a median of 106 cells/mm3 at 12 months; drug resistance rarely emerged (incidence rate 3.2 per 100 person-years); and the treatments were reasonably well-tolerated (incidence rate of severe adverse effects 7.8 per 100 person-years)., Conclusion: Together with previous pharmacological and clinical studies, this prospective study suggests that these generic antiretroviral drugs can be used in developing countries.

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/mm, 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/mm. 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.

We found a high seroprevalence of HIV among young women in a commercial logging area in Cameroon. The vulnerability of these young women could be related to commercial logging and the social and economic networks it induces. The environmental changes related to this industry in Equatorial Africa may facilitate HIV dissemination.

Background: Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine., Methods: 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis., Findings: At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per microL (IQR 78-167) and median plasma HIV-1 RNA was 104?736 copies per mL (40804-243787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3.1 log10 copies per mL (-2.5 to -3.6) and in CD4 count 83 cells per microL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0.85 (95% CI 0.73-0.92). Frequency of disease progression was 32.0 (95% CI 16.6-61.5), severe adverse effects 17.8 (7.4-42.7), and genotypic resistance mutations 7.1 (1.8-28.4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine., Interpretation: Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.

Among the irrational factors involved in medical prescribing, few studies have investigated the problem of the 'pressure to prescribe'. The aim of the present work was to quantify this 'pressure to prescribe' and to investigate some potential predisposing factors. Each instance of a patient's behaviour suggesting 'pressure to prescribe' was registered for 599 outpatient general-practice clinics. 'Pressure to prescribe' was defined as each clear request by a patient that counteracted the diagnostic and/or therapeutic strategy of physicians. The study included 246 men and 356 women (mean age: 45.4 years). 'Pressure to prescribe' was found in 142 patients, i.e. 23.7% (95% confidence interval [CI]: 20.7-27.4%). Among patients aged >18 years, the percentage increased: 27.0% (CI 95%: 23.0-31.4%), i.e. 122 of 452 patients. 'Pressure to prescribe' was first observed with requests for drugs (17.3%), biological tests (2.5%), sick-leave from work (2.09%), radiological procedures (1.1%), medical certificates (1.0%), physiotherapy (0.8%), and referral to a medical specialist (0.3%). The drugs most often associated with 'pressure to prescribe' were analgesic (27.6%), nonsteroidal plus steroidal anti-inflammatory (17.1%), gastroenterological (16.2%), anti-infectious (14.3%) drugs followed by vitamins plus antiasthenic (11.4%), antiseptic (10.5%), nasal decongestant (9.5%), 'vasodilatory' plus 'veinotonic' (8.6%) drugs. Pressure to prescribe neuropsychiatric drugs involved only 7.5% of requests. Two predisposing factors were identified: age (with an increased 'pressure to prescribe' for older people) and, less importantly, female gender (women tended to exert more 'pressure to prescribe' than men). Analysis of 'pressure to prescribe' is an important topic in the area of Social Pharmacology.

Objectives: To estimate the prevalence rates of HIV and other sexually transmitted infections (STI) among unregistered sex workers, and to describe their sociodemographic characteristics and sexual behaviours, and the reasons why they were not officially registered as sex workers, in order to design specific public health interventions., Methods: A one-stage cluster-sample survey was conducted in Dakar in 2000. Unregistered sex workers were interviewed in randomly selected establishments (official and clandestine bars, brothels and nightclubs), and blood, endocervical and vaginal samples were collected for laboratory diagnosis., Results: A total of 390 women with a median age of 29 years were recruited. One-seventh of them were under the legal age for prostitution in Senegal (21 years). The median length of prostitution was 24 months and 73.5% of the women stated regular prostitution. Three-quarters of the women were found to have markers for at least one infection. The prevalence rates were as follows: HIV-1, 6.0%; HIV-2, 3.6%; HIV-1+2, 0.4%; syphilis, 23.8%; gonorrhea, 22.0%; chlamydial infection, 20.0%; trichomoniasis, 22.4%; candidiasis, 19.0%; and bacterial vaginosis, 28.8%. The main reported reason for non-registration was ignorance of the legal system and its procedures (19.4%); 18.9% of the women refused to register. One-third of the women reported that their clients used condoms inconsistently or never., Conclusion: This survey suggests that a multidimensional public health response is needed in Senegal, comprising legal information, downwards revision of the legal age for prostitution, and specific medical follow-up based on education, condom promotion and management of STI for non-registered sex workers.

Objective: To 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)., Methods: A 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., Results: At 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 antitubercular 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., Conclusion: In 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.

In Yaounde, Cameroon, HIV-1 group-specific V3 serology on 1469 HIV-positive samples collected between 1996 and 2001 revealed that group O infections remained constant around 1% for 6 years. Only one group N sample was identified and 4.3% reacted with group M and O peptides. Although the sensitivity of the group-specific polymerase chain reaction (PCR) in two genomic regions was not optimal, we confirmed, in at least 6 of 49 (12.2%) dual O/M seropositive samples and in 1 of 9 group O samples, dual infection with group O and M viruses (n = 4) or with group O or M virus and an intergroup recombinant virus (n = 3). Partial env (V3-V5) sequences on a subset of 295 samples showed that at least eight subtypes and five circulating recombinant forms (CRFs) of HIV-1 group M co-circulate; more than 60% were CRF02&#95;AG and 11% had discordant subtype/CRF designations between env and gag. Similarly as for subtype B, the proportion of syncytium-inducing strains increased when CD4 counts were low in CRF02&#95;AG-infected patients. The V3-loop charge was significantly lower for non-syncytium-inducing strains than for syncytium-inducing strains but cannot be used as an individual marker to predict phenotype. The two predominant HIV-1 variants in Africa, CRF02&#95;AG and subtype C, thus have different biological characteristics.

To compare human immunodeficiency virus (HIV) type 1 disease progression in patients infected by the predominant strain circulating recombinant form (CRF) 02&#95;AG in western and west-central Africa and in patients infected by other strains, a prospective multicenter cohort study was conducted in Cameroon and Senegal. Among the 335 patients, a broad HIV-1 group M subtype diversity was observed in the envelope V3-V5 region, but strain CRF02&#95;AG predominated in both Cameroon and Senegal (61.2% and 62.9%, respectively; P<.8). Multivariate analyses showed no difference between patients infected by CRF02 strains and those infected by other strains in terms of survival (adjusted hazards ratio [HR], 1.16; 95% confidence interval [CI], 0.76-1.78; P=.5), clinical disease progression (HR, 0.79; 95% CI, 0.50-1.25; P=.3), or square root CD4 cell decline (regression coefficient, -0.01; 95% CI, -0.82 to 0.81; P=.9). This study suggests that the predominance of HIV-1 CRF02&#95;AG strain in western and west-central Africa should have no major clinical consequences.

Objective: To study the feasibility, effectiveness, adherence, toxicity and viral resistance in an African government HAART initiative., Methods: A 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., Results: Fifty-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 approximately 2.5 log10 copies/ml. The CD4 cell count rose by a median of 82, 147 and 180 x 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., Conclusion: This 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.