A Seronegative Case of HIV-1 Subtype C Infection in Botswana

Novitsky, Vladimir; Gaolathe, Tendani; Woldegabriel, Elias; Makhema, Joseph; Essex, M.

doi:10.1086/520683

Cited by 19 publications

(8 citation statements)

References 15 publications

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“…Although HIV-1 subtyping was not performed systematically for all individuals included in the seven BHP cohorts analyzed, our previous studies provide strong evidence for the overwhelming dominance of HIV-1 subtype C as the etiologic agent of the HIV/AIDS epidemic in Botswana [27], [39], [40], [41]. According to the HIV Sequence Database at LANL [42], 99.4% of the deposited 1,425 sequences from Botswana belong to HIV-1 subtype C. Therefore, we assume that the vast majority of subjects in this study are infected with HIV-1 subtype C.…”

Section: Methodsmentioning

confidence: 98%

“…The study was designed to evaluate potential trends between viral load and viral genetic diversity in acute and early HIV-1 subtype C infection, to determine the relationship between virologic parameters and viral set-point, and to identify immunological parameters that correlate with viral set-point in primary HIV-1 subtype C infection. All subjects included in the longitudinal analysis were genotyped and were found to be infected with HIV-1 subtype C. Results of the study were reported elsewhere [27], [39], [41], [43], [44], [45]. The primary infection cohort was comprised of individuals with estimated time of seroconversion.…”

Section: Methodsmentioning

confidence: 99%

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HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

et al. 2010

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The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log10) and cART-initiating cohorts (5.1–5.3 log10) by about one log10. The proportion of individuals with high (≥50,000 (4.7 log10) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log10) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities.

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Section: Methodsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

et al. 2010

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“…The simultaneous detection of HIV antigens (p24) and anti-HIV antibodies by fourth-generation assays reduced the window period. Despite these efforts, the performance of certain serological assays is actually still suboptimal, although reliable HIV testing is a critical entry point for patients in need of ART [24][25][26][27].…”

Section: Genetic Diversity and Hiv Diagnosismentioning

confidence: 99%

Genetic diversity among human immunodeficiency virus-1 non-B subtypes in viral load and drug resistance assays

Peeters

Aghokeng

Delaporte

2010

Clinical Microbiology and Infection

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The tremendous diversity of human immunodeficiency virus (HIV)-1 strains circulating worldwide has an important impact on almost all aspects of the management of this infection, from the identification of infected persons, through treatment efficacy and monitoring, and prevention strategies such as vaccine design. The areas where HIV-1 genetic diversity is highest are those where the majority of patients in need of treatment and biological monitoring live. With increased access to treatment in these areas, it is expected that the demand for monitoring tools such as viral load assays and resistance tests will also increase, and their reliability will be critical. Regular updates of these assays during the last two decades have aimed at improving their performances in different ways that include their reliability with different HIV-1 strains. We here review to what extent HIV-1 genetic diversity still limits or not the use of currently available viral load and resistance tests.

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“…Inclusion of HIV-1 group O antigens or the use of broadly cross-reactive antigens reduced limitations related to the high genetic diversity of HIV [5] and the simultaneous detection of HIV antigens (p24) and anti-HIV antibodies by fourth generation assays reduced the window period [6], [7]. Despite these efforts, the performance of certain serological assays is still suboptimal as illustrated by some studies [8]–[10] and the high rate of HIV indeterminate results generated by HIV serological tests remains a major concern in African countries [11]–[13].…”

Section: Introductionmentioning

confidence: 99%

Inaccurate Diagnosis of HIV-1 Group M and O Is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon

et al. 2009

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BackgroundIncreased access to HIV testing is essential in working towards universal access to HIV prevention and treatment in resource-limited countries. We here evaluated currently used HIV diagnostic tests and algorithms in Cameroon for their ability to correctly identify HIV infections.MethodsWe estimated sensitivity, specificity, and positive and negative predictive values of 5 rapid/simple tests, of which 3 were used by the national program, and 2 fourth generation ELISAs. The reference panel included 500 locally collected samples; 187 HIV -1 M, 10 HIV-1 O, 259 HIV negative and 44 HIV indeterminate plasmas.ResultsNone of the 5 rapid assays and only 1 ELISA reached the current WHO/UNAIDS recommendations on performance of HIV tests of at least 99% sensitivity and 98% specificity. Overall, sensitivities ranged between 94.1% and 100%, while specificities were 88.0% to 98.8%. The combination of all assays generated up to 9% of samples with indeterminate HIV status, because they reacted discordantly with at least one of the different tests. Including HIV indeterminate samples in test efficiency calculations significantly decreased specificities to a range from 77.9% to 98.0%. Finally, two rapid assays failed to detect all HIV-1 group O variants tested, with one rapid test detecting only 2 out of 10 group O specimens.ConclusionIn the era of ART scaling-up in Africa, significant proportions of false positive but also false negative results are still observed with HIV screening tests commonly used in Africa, resulting in inadequate treatment and prevention strategies. Depending on tests or algorithms used, up to 6% of HIV-1 M and 80% of HIV-1 O infected patients in Cameroon do not receive ART and adequate counseling to prevent further transmission due to low sensitivities. Also, the use of tests with low specificities could imply inclusion of up to 12% HIV negative people in ART programs and increase budgets in addition to inconveniences caused to patients.

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A Seronegative Case of HIV-1 Subtype C Infection in Botswana

Cited by 19 publications

References 15 publications

HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

Genetic diversity among human immunodeficiency virus-1 non-B subtypes in viral load and drug resistance assays

Inaccurate Diagnosis of HIV-1 Group M and O Is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon

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