Heterosexual Transmission of HIV-1 Despite Reported Use of ART in Couples from Zambia and Rwanda Open Access

Goldberg, Alec (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/hq37vp43g?locale=en
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Abstract

Background:

The use of antiretroviral therapy (ART) has become a common and effective form of HIV-1 treatment. The effectiveness of ART in preventing transmission was established by the HPTN 052 trial, which reported a 96% reduction in transmission between discordant couples with the early initiation of ART in the HIV-1 positive partners (1) . In this study we sought to understand why HIV-1 transmission occurred in Zambian and Rwandan serodiscordant couples despite the reported use of highly effective antiretroviral treatment.

Methods:

We selected 9 Zambian and 8 Rwandan early seroconverting/RNA positive couples where the chronic partner reported ART use for at least one month prior to initial testing. As a follow up study, we identified 50 Zambian non-transmitting serodiscordant couples where the positive partner self reported ART use to determine if a significant fraction of Zambian partners who claim to be on ART are non-adherent or resistant to ART. Plasma samples from the transmitting/positive partners were subjected to mass spectroscopy to determine if antiretroviral (ARV) drug(s) were present and quantitative RT-PCR to measure the HIV-1 viral load. Viral genotyping was performed for the transmitting partner and seroconverter to identify drug resistance mutations (DRMs).

Results:

Seven out of the nine Zambian transmitting partners had no detectable ARVs in the plasma. Of the two index partners with detectable ARVs, only one had effective concentrations. We detected DRMs in the transmitting partner and most were passed on to the seroconverting partner. In the follow up study of 50 Zambian newly identified serodiscordant couples, only 8% of the positive partners had no detectable ARVs in the plasma. Out of the 8 Rwandan serodiscordant transmitting couples, five transmitting partners had multiple detectable ARVs, two had one detectable ARV, and one had no detectable ARVs.

Conclusions:

Our analysis of Zambian and Rwandan serodiscordant couples exemplifies that ART alone is not sufficient to prevent HIV-1 transmission. The development of a low cost viral load test is needed in low-income countries to detect lack of adherence to ART and antiretroviral treatment failure. Additionally, our data reveals the need for measures to educate the population about the benefits and the importance of adhering to ART.

Table of Contents

Table of Contents

INTRODUCTION: 1

METHODS: 7

Study Population: 7

Mass Spectroscopy I: 7

Mass Spectroscopy II: 8

Viral Load Testing: 9

RT-PCR Screening Procedure For Sample Viral RNA: 9

Viral Genotyping: 10

RESULTS: 12

Analysis of 9 Zambian Transmission Pairs: 12

VL Quantitation: 12

HPLC Analysis of ARVs: 12

Sequence Analysis for DRMs: 13

Analysis of 50 Zambian Discordant Couples for Adherence and Resistance: 13

Qualitative RT-PCR Screening: 13

VL Quantitation: 14

HPLC Analysis of ARVs: 14

Sequence Analysis for DRMs: 15

Analysis of 8 Rwandan Transmission Pairs: 15

VL Quantitation: 16

HPLC Analysis of ARVs: 16

DISCUSSION: 17

FIGURES AND TABLES: 22

Table 1: 22

Figure 1: 22

Table 2: 23

Figure 2: 23

Table 3: 24

Figure 3: 24

Table 4: 25

Table 5: 25

Figure 5: 26

Table 6: 27

Table 7: 27

Table 8: 28

Table 9: 28

Table 10: 29

Table 11: 29

Table 12: 30

REFERENCES: 31

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