Systemic structural gender discrimination and inequality in the health workforce: theoretical lenses for gender analysis, multi-country evidence and implications for implementation and HRH policy.

This commentary brings together theory, evidence and lessons from 15 years of gender and HRH analyses conducted in health systems in six WHO regions to address selected data-related aspects of WHO's 2016 Global HRH Strategy and 2022 Working for Health Action Plan. It considers useful theoretical lenses, multi-country evidence and implications for implementation and HRH policy. Systemic, structural gender discrimination and inequality encompass widespread but often masked or invisible patterns of gendered practices, interactions, relations and the social, economic or cultural background conditions that are entrenched in the processes and structures of health systems (such as health education and employment institutions) that can create or perpetuate disadvantage for some members of a marginalized group relative to other groups in society or organizations. Context-specific sex- and age-disaggregated and gender-descriptive data on HRH systems' dysfunctions are needed to enable HRH policy planners and managers to anticipate bottlenecks to health workforce entry, flows and exit or retention. Multi-method approaches using ethnographic techniques reveal rich contextual detail. Accountability requires that gender and HRH analyses measure SDGs 3, 4, 5 and 8 targets and indicators. To achieve gender equality in paid work, women also need to achieve equality in unpaid work, underscoring the importance of SDG target 5.4. HRH policies based on principles of substantive equality and nondiscrimination are effective in countering gender discrimination and inequality. HRH leaders and managers can make the use of gender and HRH evidence a priority in developing transformational policy that changes the actual conditions and terms of health workers' lives and work for the better. Knowledge translation and intersectoral coalition-building are also critical to effectiveness and accountability. These will contribute to social progress, equity and the realization of human rights, and expand the health care workforce. Global HRH strategy objectives and UHC and SDG goals will more likely be realized.

Effect of Human Immunodeficiency Virus Infection on Human Papillomavirus Clearance Among Women in Senegal, West Africa.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer. METHODS: Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV negative) and HIV type (HIV-1 vs HIV-2 vs dual HIV-1/HIV-2) on clearance of type-specific HPV infection. Analyses were stratified by incident versus prevalent HPV infection. RESULTS: Incident HPV infections in HIV-positive women were less likely to clear than those in HIV-negative women (adjusted hazard ratio [HR] = 0.60; 95% confidence interval [CI], .38-.94). Among HIV-positive women, HIV-2-infected women and HIV-1/2 dually infected women were more likely to clear HPV incident infections than HIV-1-infected women (HR = 1.66; 95% CI, .95-2.92 and HR = 2.17; 95% CI, 1.12-4.22, respectively). Incident HPV infections in HIV-positive women with CD4 cell count ≤500 cells/µL were less likely to clear than those in HIV-positive women with CD4 cell count >500 cells/µL (HR = 0.65; 95% CI, .42-1.01). No significant associations were observed for prevalent HPV infections. CONCLUSIONS: HIV infection reduced the likelihood of clearance of incident HPV infection. Furthermore, among HIV-positive women, low CD4 cell count and dual HIV infection were each associated with reduced likelihood of clearance.

Long-term Experience and Outcomes of Programmatic Antiretroviral Therapy for Human Immunodeficiency Virus Type 2 Infection in Senegal, West Africa.

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 (< 50 copies/mL) at enrollment increased over calendar time. Over the study period, 76.7% of plasma viral loads for participants receiving ART were suppressed, and median CD4 gain was 84 cells/µL in participants' first 2 years on study. Since the UNAIDS 90-90-90 strategy was published, 88.1% of viral loads were suppressed. Fifteen percent of patients experienced virologic failure with no known resistance mutations, while 56% had evidence of multiclass drug resistance. 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.

[HIV-2 infection in Senegal: virological failures and resistance to antiretroviral drugs (ARVs)]. / Infection à VIH-2 au Sénégal: échecs virologiques et résistances aux antirétroviraux (ARV).

INTRODUCTION: HIV-2, endemic in West Africa, has a natural resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) which makes it difficult to treat it in developing countries. METHODS: We conducted a descriptive, longitudinal, prospective study over the period November 2005-June 2017. Virologic failure has been defined as any viral load greater than 50 copies/ml after 6 months of ARV treatment administered twice. Assays for detecting drug-resistance mutations was performed in the protease-coding region and in the reverse transcriptase-coding region. RESULTS: Data from a total of 110 patients were collected. The patients had a median age of 46 years (ranging from 18 to 67) with a sex-ratio F/M of 2.54. At inclusion, viral load could be assessed in 44% of cases with a median of 935cp/ml (ranging from 17 to 144038). Antiretroviral regimen consisted of a combination of 2 NRTIs and 1IP in 94% of cases. The median follow-up was 1200 days (ranging from 1 to 3840); 94 then 76 patients completed their 12-month and 24-month assessments respectively. At 24-month follow-up, 39 patients had virologic failure, reflecting a prevalence of 39% estimated at 33% at 12-month follow-up and at 11% at 24-month follow-up; NRTIs resistance was observed in 45% of patients, IP resistance in 41% of patients while multi-NRTIs resistance and multi-IP resistance in 30% of patients. CONCLUSION: Currently, there is an urgent need to make available the new therapeutic classes of ARV for second line ART for patients living with HIV-2 with therapeutic failure in resource-limited settings.

Female genital mutilation and noninvasive cervical abnormalities and invasive cervical cancer in Senegal, West Africa: A retrospective study.

Female genital mutilation or cutting (FGM/C) is a traditional practice that affects a significant portion of women in sub-Saharan Africa, Egypt, areas of the Middle East and some countries in Asia. While clinical and epidemiological studies have established a close association between inflammation and carcinogenesis, particularly in epithelial cancers, the relationship between FGM/C and cervical cancer is not well known. We performed a secondary analysis using combined data from six research studies conducted in and around Dakar, Senegal from 1994 to 2012. Study subjects included both asymptomatic women who presented to outpatient clinics but were screened for cervical cancer, and women with cancer symptoms who were referred for cervical cancer treatment. We used unconditional logistic regression to estimate adjusted pooled odds ratios (ORs) and 95% confidence intervals (CI) for associations between FGM/C and (1) Invasive cervical cancer (ICC) and (2) noninvasive cervical abnormalities. After adjusting for confounding, women with ICC were 2.50 times more likely to have undergone FGM/C than women without cervical abnormalities (95% CI, 1.28-4.91). Restricting to HPV-positive women increased the strength of the association (OR = 4.23; 95% CI 1.73-10.32). No significant associations between FGM/C and noninvasive cervical abnormalities were observed, except in commercial sex workers with FGM/C (OR = 2.01; 95% CI 1.19-3.40). The potential increased risk for ICC suggested by our study warrants further examination. Study results may impact cancer prevention efforts in populations where FGM/C is practiced and draw awareness to the additional health risks associated with FGM/C.

In Vitro Antiviral Activity of Cabotegravir against HIV-2.

We examined the antiviral activity of the integrase inhibitor (INI) cabotegravir against HIV-2 isolates from INI-naive individuals. HIV-2 was sensitive to cabotegravir in single-cycle and spreading-infection assays, with 50% effective concentrations (EC50s) in the low to subnanomolar range; comparable results were obtained for HIV-1 in both assay formats. Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for antiretroviral therapy and preexposure prophylaxis in HIV-2-prevalent settings.

A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa.

Background: There is an urgent need for safe and effective antiretroviral therapy (ART) for human immunodeficiency virus type 2 (HIV-2) infection. We undertook the first clinical trial of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2-infected individuals in Senegal, West Africa. Methods: HIV-2-infected, ART-naive adults with World Health Organization stage 3-4 disease or CD4 count <750 cells/µL were eligible for this 48-week, open-label trial. We analyzed HIV-2 viral loads (VL), CD4 counts, clinical and adverse events, mortality, and loss to follow-up. Results: We enrolled 30 subjects who initiated E/C/F/TDF. Twenty-nine subjects completed 48 weeks of follow-up. The majority were female (80%). There were no deaths, no new AIDS-associated clinical events, and 1 loss to follow-up. The median baseline CD4 count was 408 (range, 34-747) cells/µL, which increased by a median 161 (range, 27-547) cells/µL at week 48. Twenty-five subjects had baseline HIV-2 VL of <50 copies/mL of plasma. In those with detectable HIV-2 VL, the median was 41 (range, 10-6135) copies/mL. Using a modified intent-to-treat analysis (US Food and Drug Administration Snapshot method), 28 of 30 (93.3%; 95% confidence interval, 77.9%-99.2%) had viral suppression at 48 weeks. The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48. There were 8 grade 3-4 adverse events; none were deemed study related. Adherence and acceptability were good. Conclusions: Our data suggest that E/C/F/TDF, a once-daily, single-tablet-regimen, is safe, effective, and well tolerated. Our findings support the use of integrase inhibitor-based regimens for HIV-2 treatment. Clinical Trials Registration: NCT02180438.

Detection and differentiation of HIV-2 using the point-of-care Alere q HIV-1/2 Detect nucleic acid test.

BACKGROUND: The Alere q HIV-1/2 Detect test (Alere Detect) is a rapid point-of-care (POC) nucleic acid test (NAT) that can detect and differentiate HIV-1 and HIV-2 in 25-µL whole blood or plasma samples. The Alere Detect test has been validated for early infant diagnosis of HIV-1 infection, and it is the only POC NAT device currently known to detect HIV-2, which is endemic in West Africa. OBJECTIVES: To evaluate the sensitivity detecting HIV-2 RNA and the differential performance of the Alere Detect. STUDY DESIGN: Plasma samples from non-HIV (n=4), HIV-1 (n=22), HIV-2 (n=111; 29 Group A, 2 Group B) and HIV-1/HIV-2 dually-seropositive (n=8) participants in Senegal and the United States and HIV-2 reference strains (3 Group A, 1 Group B) were tested by Alere Detect, Abbott RealTime HIV-1 and the University of Washington HIV-2 RNA quantitative (UW HIV-2) assays. RESULTS: The Alere Detect correctly differentiated between HIV-1 and HIV-2 in all 80 (100%) patient samples with detectable HIV RNA (n=20 HIV-1, 60 HIV-2). The overall HIV-2 detection concordance between Alere Detect and the UW HIV-2 assay was 68% (54/80); the concordance improved to 100% (30/30) for samples with HIV-2 RNA >300copies/mL. Neither assay detected HIV-2 RNA in 31 of 111 HIV-2 seropositive samples. CONCLUSIONS: The Alere Detect test is a novel device detecting HIV RNA in clinical samples, and differentiating HIV-1 and HIV-2 with a high level of specificity. It has the potential for use as a rapid HIV-2 NAT-based diagnosis tool in resource-limited settings and to confirm HIV-2 infection for the CDC 4th generation HIV-1/2 diagnostic algorithm.

MK-8591 (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine) Exhibits Potent Activity against HIV-2 Isolates and Drug-Resistant HIV-2 Mutants in Culture.

There is a pressing need to identify more effective antiretroviral drugs for HIV-2 treatment. Here, we show that the investigational compound MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is highly active against group A and B isolates of HIV-2; 50% effective concentrations [EC50] for HIV-2 were, on average, 4.8-fold lower than those observed for HIV-1. MK-8591 also retains potent activity against multinucleoside-resistant HIV-2 mutants (EC50 ≤ 11 nM). These data suggest that MK-8591 may have antiviral activity in HIV-2-infected individuals.

The dimensions of food insecurity and malnutrition among people living with HIV in Senegal, West Africa.

An understanding of the factors contributing to food insecurity and malnutrition among people living with HIV (PLHIV) in Senegal is urgently needed in order to develop effective interventions. The goals of this study were to identify differences in the dimensions of food security among PLHIV in Dakar versus Ziguinchor, Senegal, to determine which of these dimensions are most predictive of severe food insecurity, and to identify factors associated with malnutrition. We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. Interviews were conducted with ninety-five food insecure, HIV-infected subjects. Daily household income and daily food expenditure per household member were the strongest predictors of severe food insecurity. The practice of agriculture, livestock ownership, nutritional status, and HIV outcomes were not predictive of severe food insecurity. CD4 count <350/mm3 was the strongest predictor of malnutrition. Severe food insecurity, daily household income, daily food expenditure per household member, dietary diversity score, skipping meals, the practice of agriculture, livestock ownership, ART status, and adherence were not predictive of malnutrition. This is the first study to analyze the dimensions of food security among PLHIV in Senegal. We discovered important differences in food access, availability, stability, and utilization in Dakar versus Ziguinchor. We found that economic access was the strongest predictor of severe food insecurity and poorly controlled HIV was the strongest predictor of malnutrition. Our findings suggest that the interventions needed to address food insecurity differ from those necessary to target malnutrition, and that effective interventions may differ in Dakar versus Ziguinchor. Furthermore, this study highlights a need for a greater understanding of the relationship between HIV and malnutrition among individuals receiving ART in resource-limited settings.

A Comparison of the Natural History of HPV Infection and Cervical Abnormalities among HIV-Positive and HIV-Negative Women in Senegal, Africa.

Background: There is evidence of an interaction between HIV and human papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer mortality among HIV-positive women. This study aims to determine how the natural history of cervical HPV infection differs by HIV status.Methods: A total of 1,320 women (47% were positive for HIV-1 and/or HIV-2) were followed for an average of two years in Senegal, West Africa between 1994 and 2010. Cytology (with a sub-sample of histology) and HPV DNA testing were performed at approximately 4-month intervals yielding data from over 7,900 clinic visits. Competing risk modeling was used to estimate rates for transitioning between three clinically relevant natural history stages: Normal, HPV, and HSIL (high-grade squamous intraepithelial lesions). Among HIV-positive women, exploratory univariate analyses were conducted examining the impact of HPV type, infection with multiple HPV types, HIV type, CD4+ count, and age.Results: HIV-positive women had higher rates of progression and lower rates of regression compared with HIV-negative women (i.e., adverse transitions). HIV-positive women had a 2.55 [95% confidence interval (CI), 1.69-3.86; P < 0.0001] times higher rate of progression from HPV to HSIL than HIV-negative women (with 24-month absolute risks of 0.18 and 0.07, respectively). Among HIV-positive women, HPV-16/18 infection and CD4+ count <200/mm3 were associated with adverse transitions.Conclusions: Adverse HIV effects persist throughout HPV natural history stages.Impact: In the limited-resource setting of sub-Saharan Africa where cervical cancer screening is not widely available, the high-risk population of HIV-positive women may be ideal for targeted screening. Cancer Epidemiol Biomarkers Prev; 26(6); 886-94. ©2017 AACR.

Clinical validation of a novel diagnostic HIV-2 total nucleic acid qualitative assay using the Abbott m2000 platform: Implications for complementary HIV-2 nucleic acid testing for the CDC 4th generation HIV diagnostic testing algorithm.

BACKGROUND: The 2014 CDC 4th generation HIV screening algorithm includes an orthogonal immunoassay to confirm and discriminate HIV-1 and HIV-2 antibodies. Additional nucleic acid testing (NAT) is recommended to resolve indeterminate or undifferentiated HIV seroreactivity. HIV-2 NAT requires a second-line assay to detect HIV-2 total nucleic acid (TNA) in patients' blood cells, as a third of untreated patients have undetectable plasma HIV-2 RNA. OBJECTIVES: To validate a qualitative HIV-2 TNA assay using peripheral blood mononuclear cells (PBMC) from HIV-2-infected Senegalese study participants. STUDY DESIGN: We evaluated the assay precision, sensitivity, specificity, and diagnostic performance of an HIV-2 TNA assay. Matched plasma and PBMC samples were collected from 25 HIV-1, 30 HIV-2, 8 HIV-1/-2 dual-seropositive and 25 HIV seronegative individuals. Diagnostic performance was evaluated by comparing the outcome of the TNA assay to the results obtained by the 4th generation HIV screening and confirmatory immunoassays. RESULTS: All PBMC from 30 HIV-2 seropositive participants tested positive for HIV-2 TNA including 23 patients with undetectable plasma RNA. Of the 30 matched plasma specimens, one was HIV non-reactive. Samples from 50 non-HIV-2 infected individuals were confirmed as non-reactive for HIV-2 Ab and negative for HIV-2 TNA. The agreement between HIV-2 TNA and the combined immunoassay results was 98.8% (79/80). Furthermore, HIV-2 TNA was detected in 7 of 8 PBMC specimens from HIV-1/HIV-2 dual-seropositive participants. CONCLUSIONS: Our TNA assay detected HIV-2 DNA/RNA in PBMC from serologically HIV-2 reactive, HIV indeterminate or HIV undifferentiated individuals with undetectable plasma RNA, and is suitable for confirming HIV-2 infection in the HIV testing algorithm.

High Prevalence of Severe Food Insecurity and Malnutrition among HIV-Infected Adults in Senegal, West Africa.

BACKGROUND: Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes. METHODS: We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. RESULTS: One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01). CONCLUSIONS: Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population.

The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the in vitro activity of the investigational nucleoside analog BMS-986001 (2',3'-didehydro-3'-deoxy-4'-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4'-ethynyl stavudine, or 4'-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nM. In contrast, EC50s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC50 for HIV-2 was 9.5-fold lower than that for HIV-1 (64 ± 18 nM versus 610 ± 200 nM, respectively; mean ± standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture.

Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal: implications for second-line therapy.

Protease inhibitor (PI)-based antiretroviral therapy (ART) can effectively suppress HIV-2 plasma load and increase CD4 counts; however, not all PIs are equally active against HIV-2, and few data exist to support second-line therapy decisions. To identify therapeutic options for HIV-2 patients failing ART, we evaluated the frequency of PI resistance-associated amino acid changes in HIV-2 sequences from a cohort of 43 Senegalese individuals receiving unboosted indinavir (n = 18 subjects)-, lopinavir/ritonavir (n = 4)-, or indinavir and then lopinavir/ritonavir (n = 21)-containing ART. Common protease substitutions included V10I, V47A, I54M, V71I, I82F, I84V, L90M, and L99F, and most patients harbored viruses containing multiple changes. Based on genotypic data, we constructed a panel of 15 site-directed mutants of HIV-2ROD9 containing single- or multiple-treatment-associated amino acid changes in the protease-encoding region of pol. We then quantified the susceptibilities of the mutants to the HIV-2 "active" PIs saquinavir, lopinavir, and darunavir using a single-cycle assay. Relative to wild-type HIV-2, the V47A mutant was resistant to lopinavir (6.3-fold increase in the mean 50% effective concentration [EC50]), the I54M variant was resistant to darunavir and lopinavir (6.2- and 2.7-fold increases, respectively), and the L90M mutant was resistant to saquinavir (3.6-fold increase). In addition, the triple mutant that included I54M plus I84V plus L90M was resistant to all three PIs (31-, 10-, and 3.8-fold increases in the mean EC50 for darunavir, saquinavir, and lopinavir, respectively). Taken together, our data demonstrate that PI-treated HIV-2 patients frequently harbor viruses that exhibit complex patterns of PI cross-resistance. These findings suggest that sequential PI-based regimens for HIV-2 treatment may be ineffective.

HIV-2 integrase variation in integrase inhibitor-naïve adults in Senegal, West Africa.

BACKGROUND: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance. METHODS: We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1. RESULTS: No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein. CONCLUSION: Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.