High level of treatment failure and drug resistance to first-line antiretroviral therapies among HIV-infected children receiving decentralized care in Senegal.

BACKGROUND: In Senegal in 2015, an estimated 4800 children were living with HIV, with 1200 receiving ARV treatment, of whom half had follow-up care in decentralized sites outside Dakar. However, until now no studies have determined the efficacy of pediatric treatment in decentralized settings, even though the emergence of viral resistance, particularly among children in Africa, is a well-known phenomenon. This study aimed to assess the virological status of HIV-infected children in all decentralized facilities to help improve access to quality care. METHODS: A cross-sectional epidemiological and virological study was conducted in all of Senegal's regions, except Dakar, between March and June 2015 and sought to include all HIV-infected children and adolescents (0-19 years), treated or not with ARVs. Socio-demographic and clinical data and a blood sample on blotting paper were collected for children from treatment sites. Samples were routed on public transportation, assisted by a network of community health workers. A viral load (VL) assay was performed for each child, followed by genotyping when it exceeded 1000 copies/mL (3 log10). RESULTS: Of the 851 identified children, 666 (78%) were enrolled in the study. Half of the children were girls, and the average age was 8 years (6 months-19 years). Most of the children (96.7%) were infected with HIV-1, and 90% were treated with ART, primarily with AZT + 3TC + NVP/EFV therapeutic regimen. The median duration of time on ART was 21 months (1-129). VL was measured for 2% of children before this study. Almost two-thirds (64%) of the children are experiencing virological failure. Among them, there was resistance to at least one drug for 86.5% of cases. Also, 25% children presented resistance to one drug and 40% to two out of three. For nearly one-third of the children presenting resistance, none of the three drugs of the treatment was active. Factors associated with virological failure were male sex, follow-up by a generalist rather than a specialist, and treatment interruptions. CONCLUSIONS: We observed a high level of virological failure and a high percentage of viral resistance among children receiving health care in decentralized facilities in Senegal.

Implementing services for Early Infant Diagnosis (EID) of HIV: a comparative descriptive analysis of national programs in four countries.

BACKGROUND: There is a significant increase in survival for HIV-infected children who have early access to diagnosis and treatment. The goal of this multi-country review was to examine when and where HIV-exposed infants and children are being diagnosed, and whether the EID service is being maximally utilized to improve health outcomes for HIV-exposed children. METHODS: In four countries across Africa and Asia existing documents and data were reviewed and key informant interviews were conducted. EID testing data was gathered from the central testing laboratories and was then complemented by health facility level data extraction which took place using a standardized and validated questionnaire RESULTS: In the four countries reviewed from 2006 to 2009 EID sample volumes rose dramatically to an average of >100 samples per quarter in Cambodia and Senegal, >7,000 samples per quarter in Uganda, and >2,000 samples per quarter in Namibia. Geographic coverage of sites also rapidly expanded to 525 sites in Uganda, 205 in Namibia, 48 in Senegal, and 26 in Cambodia in 2009. However, only a small proportion of testing was done at lower-level health facilities: in Uganda Health Center IIs and IIIs comprised 47% of the EID collection sites, but only 11% of the total tests, and in Namibia 15% of EID sites collected >93% of all samples. In all countries except for Namibia, more than 50% of the EID testing was done after 2 months of age. Few sites had robust referral mechanisms between EID and ART. In a sub-sample of children, we noted significant attrition of infants along the continuum of care post testing. Only 22% (Senegal), 37% (Uganda), and 38% (Cambodia) of infants testing positive by PCR were subsequently initiated onto treatment. In Namibia, which had almost universal EID coverage, more than 70% of PCR-positive infants initiated ART in 2008. CONCLUSIONS: While EID testing has expanded dramatically, a large proportion of PCR- positive infants are initiated on treatment. As EID services continue to scale-up, more programmatic attention and support is needed to retain HIV-exposed infants in care and ensure that those testing positive initiate treatment in a timely manner. Namibia's experience demonstrates that it is feasible for a rural, low-income country to achieve high national coverage of infant testing and treatment.

Reduction in risk-taking behaviors among MSM in Senegal between 2004 and 2007 and prevalence of HIV and other STIs. ELIHoS Project, ANRS 12139.

An epidemiological survey conducted in Senegal in 2004 among men having sex with men (MSM) revealed high HIV prevalence and a high rate of risky behaviors within this population. Consequently, several prevention campaigns targeting MSM were implemented. A second survey was carried out in 2007 to assess the impact of these measures. This paper aims to examine trends in HIV and STI prevalence and in sexual behaviors between 2004 and 2007. The two surveys were conducted in four urban sites among 440 and 501 MSM--recruited using the snowball sampling method--in 2004 and 2007, respectively. A similar methodology was applied for both surveys. This consisted of a closed-ended questionnaire concerning socio-demographic, behavioral, and biomedical information plus a clinical examination including urine and blood tests to detect STIs and HIV infection. Between 2004 and 2007, the frequency of different sexual practices reported by MSM remained stable, but condom use for each type of sexual practice rose. The percentage of men who reported consistent condom use during previous-month anal sex has increased by about 35% (p<0.01). The percentage of men who reported consistent condom use during previous-month non-commercial sex with women has increased by 14% (p<0.01). HIV prevalence remained stable from 22.4% [95% CI: 18.6-26.8] in 2004 to 21.8% [95% CI: 18.3-25.7] in 2007 (adjusted OR = 1.05, p=0.8). Gonorrhea prevalence decreased from 5.5% [95% CI: 3.6-8.3] in 2004 to 2.6% [95% CI: 1.5-4.5] in 2007 (adjusted OR=0.5, p=0.07). The prevention campaigns, STI and HIV care and support programs conducted in Senegal among MSM have been followed by a reduction of risk-taking behaviors and STI prevalence among this population. Specific targeting of this group within HIV/STI prevention programs seems to be effective in decreasing sexual infections.

Quantitation of HIV-1 RNA in dried blood spots by the real-time NucliSENS EasyQ HIV-1 assay in Senegal.

Measurement of viral load in plasma remains the best marker for the follow-up of antiretroviral therapy. However, its use is limited in developing countries due to the lack of adequate facilities and equipment, and cryopreservation of plasma during storage and transportation. Practical and reliable methods adapted to field conditions for the collection, transportation and accurate measurement of HIV-1 viral load are needed for the optimum use of antiretroviral therapy in resource-limited countries. This study evaluated the use of dried blood spots (DBS) for the real-time quantitation of HIV-1 RNA levels with the NucliSENS EasyQ((R)) HIV-1 assay (bioMérieux, Lyon, France) under field conditions in Senegal (Africa). Dried blood spots and plasma from 41 patients living in suburban Dakar were used for determination of HIV-1 RNA concentrations and stability at 37 degrees C. Analysis was performed at the Dakar University Hospital laboratory. Extraction was done with the bioMérieux NucliSENS((R)) miniMAGtrade mark, and real-time detection was done with the bioMérieux NucliSENS((R)) EasyQ system. HIV-1 RNA concentrations in plasma were compared with concentrations in dried blood spots after 8 and 15 days at 37 degrees C. The study showed a strong concordance in RNA levels between plasma and dried blood spots, which appear to be very stable over time with no apparent degradation observed after 2 weeks at 37 degrees C (mean difference 0.065logIU/ml). These results suggest that the use of dried blood spots in combination with the NucliSENS EasyQ HIV-1 assay is well adapted for HIV-1 RNA level monitoring in centralized laboratories in developing countries.

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.

Prevalence of HIV and other sexually transmitted infections, and risk behaviours in unregistered sex workers in Dakar, Senegal.

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.

High frequency of HIV-1 infections with multiple HIV-1 strains in men having sex with men (MSM) in Senegal.

Circulating and unique recombinant HIV-1 strains continue to be identified and their number increases over time, suggesting that co-infection with multiple HIV-1 is frequent. In this study we analyzed to what extent dual infections with different HIV-1 variants occur in a population group with high risk behaviour, high HIV-1 prevalence and in an area where multiple HIV-1 subtypes and Circulating Recombinant Forms (CRFs) co-circulate. We studied 69 MSM with our recently developed multi-region hybridization assay (MHA), based on fluorescent probe detection for eight common variants circulating in West and West Central Africa. At least 11 (15.9%) of the 69 patients were simultaneously infected with two different HIV-1 subtypes and/or CRFs. Among the 29 samples identified as subtype C by MHA in gag, 15 (57.7%) reacted with both C1 and C2 probes. Sequence analysis suggests that the majority of the samples reactive with C1 and C2 probes are most likely infected with two different subtype C clades. Single genome amplification and DNA dilutions confirmed dual infection with subtype D and C for MSM1193, triple infection with two different C subtype strains and one CRF02_AG strain in MSM1157 and showed that MSM3017 is at least co-infected with CRF06_cpx and CRF02_AG and another strain that could not be classified. Comparison of all subtype C sequences from the MSM population and from the general population from this and previous studies confirmed the intermixing of HIV-1 variants between low-risk women and high-risk men as shown by the intermixing of subtype C variants from MSM1157 and a female patient (02SN-HALD478). Comparison of dual infection rates between the general population and MSM in Senegal, show also clearly the importance of high HIV prevalence and high risk behavior in dual infections and subsequent intermixing of HIV-1 variants which can lead to emergence and spread of new recombinants (CRFs).

Men who have sex with men (MSM) and factors associated with not using a condom at last sexual intercourse with a man and with a woman in Senegal.

BACKGROUND: Men who have sex with other men (MSM) are a vulnerable population in Africa that has been insufficiently explored. Given the high rate of bisexuality among MSM (73% in the past year), it is important to understand their risk-taking behaviors regarding both men and women. METHODOLOGY/PRINCIPAL FINDINGS: A socio-behavioral survey was carried out in 2007 among 501 MSM recruited using the snowball sampling method. We explore in this article why a condom was not used during last sexual intercourse with a man and with a woman, taking into account the respondent's characteristics, type of relationship and the context of the sexual act. In the survey, 489 men reported that they had had sexual intercourse at least once with another man during the previous year, and 358 with a man and with a woman. The main risk factors for not using a condom at last sexual intercourse with another man were having sex in a public place (aOR = 6.26 [95%CI: 2.71-14.46]), non-participation in an MSM prevention program (aOR = 3.47 [95%CI: 2.12-5.69]), a 19 years old or younger partner (aOR = 2.6 [95%CI: 1.23-4.53]), being 24 years or younger (aOR = 2.07 [95%CI: 1.20-3.58]) or being 35 years or over (aOR = 3.08 [95%CI:1.11-8.53]) and being unemployed (aOR = 0.36 [95%CI: 0.10-1.25]). The last sexual intercourse with the respondent's wife was hardly ever protected (2%). With women, the other factors were a 15 years or younger partner (aOR = 6.45 [95%CI: 2.56-16.28]), being educated (primary: aOR = 0.45 [95%CI: 0.21-0.95], secondary or higher: aOR = 0.26 [95%CI: 0.11-0.62]), being a student (aOR = 2.20 [95%CI: 1.07-4.54]) or unemployed (aOR = 3.72 [95%CI: 1.31-10.61]) and having participated in a MSM prevention program (aOR = 0.57 [95%CI: 0.34-0.93]). CONCLUSION: Having participated in a prevention program specifically targeting MSM constitutes a major prevention factor. However, these programs targeting MSM must address their heterosexual practices and the specific risks involved.

Surprisingly high prevalence of subtype C and specific HIV-1 subtype/CRF distribution in men having sex with men in Senegal.

BACKGROUND: Recent reports showed the high vulnerability for HIV infection of men who have sex with men (MSM) in Africa. Here, we report the HIV-1 variants that circulate among MSM in Senegal. METHODS: HIV-1 subtype/circulating recombinant form (CRF) was determined in an 1800-base pair fragment of pol for 70 HIV-1-positive samples from MSM. Phylogenetic trees were constructed using the neighbor-joining method with CLUSTALX. Similarity and bootstrap plots were then done for recombination analysis. The maximum likelihood approach was used for the identification of transmission clusters. RESULTS: Sixty-seven samples (95%) were from Senegalese MSM, 90% unmarried with a median age of 30 years. Fifty-five MSM had regular male partners, but 39 of 70 had also a regular female partner. The overall subtype/CRF distribution was as follows: 28 C (40%), 17 CRF02_AG (24.3%), 13 B (18.6%), 6 G (8.6%), 3 CRF09_cpx (4.3%), and 3 (4.3%) unique recombinants. In addition, 47 sequences (67.15%) were segregated into 15 transmission clusters. CONCLUSIONS: These variants circulate also among the general population or female sex workers, but the proportions are significantly different. Despite the massive stigma, the majority (80%) of MSM recognized having sex with women and could serve as a bridge for intermixing of HIV-1 variants between high-risk men and low-risk women.